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COVID-19 interrupted global poliovirus surveillance and immunization
Most (86%) of these outbreaks were caused by cVDPV2 (circulating VDPV type 2 poliovirus, which originated with the vaccine), and most occurred in Africa, according to a new study of vaccine-derived poliovirus outbreaks between Jan. 2020 and June 2021 published in the CDC’s Morbidity and Mortality Weekly Report.
The Global Polio Eradication Initiative (GPEI) was launched in 1988 and used live attenuated oral poliovirus vaccine (OPV). Since then, cases of wild poliovirus have declined more than 99.99%.
The cVDPV2 likely originated among children born in areas with poor vaccine coverage. Jay Wenger, MD, director, Polio, at the Bill and Melinda Gates Foundation, told this news organization that “the inactivated vaccines that we give in most developed countries now are good in that they provide humoral immunity, the antibodies in the bloodstream. They don’t necessarily provide mucosal immunity. They don’t make the kid’s gut immune to getting reinfected or actually immune to reproducing the virus if they get it in their gut. So we could still have a situation where everybody was vaccinated with IPV [inactivated poliovirus], but the virus could still be transmitting around because kids’ guts would still be producing the virus and there will still be transmission in your population, probably without much or any paralysis because of the IPV. As soon as that virus hit a population that was not vaccinated, they would get paralyzed.”
Dr. Wenger added, “The ideal vaccine would be an oral vaccine that didn’t mutate back and couldn’t cause these VDPVs.” Scientists developed such a vaccine, approved by the World Health Organization last year under an Emergency Use Authorization. This nOPV2 (novel oral poliovirus type 2) vaccine has been given since March 2021 in areas with the VDPD2 outbreaks. The nOPV2 should allow them to “basically stamp out the outbreaks.”
The world had almost eradicated the disease, with the last cases of polio from wild virus occurring in Nigeria, Afghanistan, and Pakistan as of 2014. Africa was declared free of wild polio in 2020 after it had been eradicated from Nigeria, which accounted for more than half of the world’s cases only a decade earlier. Now cVDPV outbreaks affect 28 African countries, plus Iran, Yemen, Afghanistan, Pakistan, Tajikistan, Malaysia, the Philippines, and Indonesia. And there was also one case in China. Globally, there were 1,335 cases of cVDPV causing paralysis during the reporting period.
The COVID-19 pandemic has had a significant impact on polio, accounting for much of this year’s increase in cases. Dr. Wenger said, “We couldn’t do any campaigns. We pretty much stopped doing outbreak response campaigns in the middle of the year because of COVID.”
The CDC report notes that many of the supplementary immunizations in response to cVDPV2 outbreaks were of “poor quality,” and prolonged delays enabled geographically expanding cVDPV2 transmission.
Steve Wassilak, MD, chief coauthor of the CDC study, told this news organization that, because of COVID, “what we’ve been lacking is a rapid response for the most part. Some of that is due to laboratory delays and shipment because of COVID’s effect on international travel.” He noted, however, that there has been good recovery in surveillance and immunization activities despite COVID. And, he added, eradication “can be done, and many outbreaks have closed even during the [COVID] outbreak.”
Dr. Wassilak said that in Nigeria, “the face of the campaign became national.” In Pakistan, much of the work is done by national and international partners.
Dr. Wenger said that in Nigeria and other challenging areas, “the approach was essentially to make direct contact with the traditional leaders and the religious leaders and the local actors in each of these populations. So, it’s really getting down to the grassroots level.” Infectious disease officials send teams to speak with individuals in the “local, traditional leader system.”
“Just talking to them actually got us a long way and giving them the information that they need. In most cases, I mean, people want to do things to help their kids,” said Dr. Wenger.
For now, the initial plan, per the CDC, is to “initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission” until a better supply of nOPV2 is available, then switch to IPVs.
Dr. Wenger and Dr. Wassilak report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most (86%) of these outbreaks were caused by cVDPV2 (circulating VDPV type 2 poliovirus, which originated with the vaccine), and most occurred in Africa, according to a new study of vaccine-derived poliovirus outbreaks between Jan. 2020 and June 2021 published in the CDC’s Morbidity and Mortality Weekly Report.
The Global Polio Eradication Initiative (GPEI) was launched in 1988 and used live attenuated oral poliovirus vaccine (OPV). Since then, cases of wild poliovirus have declined more than 99.99%.
The cVDPV2 likely originated among children born in areas with poor vaccine coverage. Jay Wenger, MD, director, Polio, at the Bill and Melinda Gates Foundation, told this news organization that “the inactivated vaccines that we give in most developed countries now are good in that they provide humoral immunity, the antibodies in the bloodstream. They don’t necessarily provide mucosal immunity. They don’t make the kid’s gut immune to getting reinfected or actually immune to reproducing the virus if they get it in their gut. So we could still have a situation where everybody was vaccinated with IPV [inactivated poliovirus], but the virus could still be transmitting around because kids’ guts would still be producing the virus and there will still be transmission in your population, probably without much or any paralysis because of the IPV. As soon as that virus hit a population that was not vaccinated, they would get paralyzed.”
Dr. Wenger added, “The ideal vaccine would be an oral vaccine that didn’t mutate back and couldn’t cause these VDPVs.” Scientists developed such a vaccine, approved by the World Health Organization last year under an Emergency Use Authorization. This nOPV2 (novel oral poliovirus type 2) vaccine has been given since March 2021 in areas with the VDPD2 outbreaks. The nOPV2 should allow them to “basically stamp out the outbreaks.”
The world had almost eradicated the disease, with the last cases of polio from wild virus occurring in Nigeria, Afghanistan, and Pakistan as of 2014. Africa was declared free of wild polio in 2020 after it had been eradicated from Nigeria, which accounted for more than half of the world’s cases only a decade earlier. Now cVDPV outbreaks affect 28 African countries, plus Iran, Yemen, Afghanistan, Pakistan, Tajikistan, Malaysia, the Philippines, and Indonesia. And there was also one case in China. Globally, there were 1,335 cases of cVDPV causing paralysis during the reporting period.
The COVID-19 pandemic has had a significant impact on polio, accounting for much of this year’s increase in cases. Dr. Wenger said, “We couldn’t do any campaigns. We pretty much stopped doing outbreak response campaigns in the middle of the year because of COVID.”
The CDC report notes that many of the supplementary immunizations in response to cVDPV2 outbreaks were of “poor quality,” and prolonged delays enabled geographically expanding cVDPV2 transmission.
Steve Wassilak, MD, chief coauthor of the CDC study, told this news organization that, because of COVID, “what we’ve been lacking is a rapid response for the most part. Some of that is due to laboratory delays and shipment because of COVID’s effect on international travel.” He noted, however, that there has been good recovery in surveillance and immunization activities despite COVID. And, he added, eradication “can be done, and many outbreaks have closed even during the [COVID] outbreak.”
Dr. Wassilak said that in Nigeria, “the face of the campaign became national.” In Pakistan, much of the work is done by national and international partners.
Dr. Wenger said that in Nigeria and other challenging areas, “the approach was essentially to make direct contact with the traditional leaders and the religious leaders and the local actors in each of these populations. So, it’s really getting down to the grassroots level.” Infectious disease officials send teams to speak with individuals in the “local, traditional leader system.”
“Just talking to them actually got us a long way and giving them the information that they need. In most cases, I mean, people want to do things to help their kids,” said Dr. Wenger.
For now, the initial plan, per the CDC, is to “initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission” until a better supply of nOPV2 is available, then switch to IPVs.
Dr. Wenger and Dr. Wassilak report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most (86%) of these outbreaks were caused by cVDPV2 (circulating VDPV type 2 poliovirus, which originated with the vaccine), and most occurred in Africa, according to a new study of vaccine-derived poliovirus outbreaks between Jan. 2020 and June 2021 published in the CDC’s Morbidity and Mortality Weekly Report.
The Global Polio Eradication Initiative (GPEI) was launched in 1988 and used live attenuated oral poliovirus vaccine (OPV). Since then, cases of wild poliovirus have declined more than 99.99%.
The cVDPV2 likely originated among children born in areas with poor vaccine coverage. Jay Wenger, MD, director, Polio, at the Bill and Melinda Gates Foundation, told this news organization that “the inactivated vaccines that we give in most developed countries now are good in that they provide humoral immunity, the antibodies in the bloodstream. They don’t necessarily provide mucosal immunity. They don’t make the kid’s gut immune to getting reinfected or actually immune to reproducing the virus if they get it in their gut. So we could still have a situation where everybody was vaccinated with IPV [inactivated poliovirus], but the virus could still be transmitting around because kids’ guts would still be producing the virus and there will still be transmission in your population, probably without much or any paralysis because of the IPV. As soon as that virus hit a population that was not vaccinated, they would get paralyzed.”
Dr. Wenger added, “The ideal vaccine would be an oral vaccine that didn’t mutate back and couldn’t cause these VDPVs.” Scientists developed such a vaccine, approved by the World Health Organization last year under an Emergency Use Authorization. This nOPV2 (novel oral poliovirus type 2) vaccine has been given since March 2021 in areas with the VDPD2 outbreaks. The nOPV2 should allow them to “basically stamp out the outbreaks.”
The world had almost eradicated the disease, with the last cases of polio from wild virus occurring in Nigeria, Afghanistan, and Pakistan as of 2014. Africa was declared free of wild polio in 2020 after it had been eradicated from Nigeria, which accounted for more than half of the world’s cases only a decade earlier. Now cVDPV outbreaks affect 28 African countries, plus Iran, Yemen, Afghanistan, Pakistan, Tajikistan, Malaysia, the Philippines, and Indonesia. And there was also one case in China. Globally, there were 1,335 cases of cVDPV causing paralysis during the reporting period.
The COVID-19 pandemic has had a significant impact on polio, accounting for much of this year’s increase in cases. Dr. Wenger said, “We couldn’t do any campaigns. We pretty much stopped doing outbreak response campaigns in the middle of the year because of COVID.”
The CDC report notes that many of the supplementary immunizations in response to cVDPV2 outbreaks were of “poor quality,” and prolonged delays enabled geographically expanding cVDPV2 transmission.
Steve Wassilak, MD, chief coauthor of the CDC study, told this news organization that, because of COVID, “what we’ve been lacking is a rapid response for the most part. Some of that is due to laboratory delays and shipment because of COVID’s effect on international travel.” He noted, however, that there has been good recovery in surveillance and immunization activities despite COVID. And, he added, eradication “can be done, and many outbreaks have closed even during the [COVID] outbreak.”
Dr. Wassilak said that in Nigeria, “the face of the campaign became national.” In Pakistan, much of the work is done by national and international partners.
Dr. Wenger said that in Nigeria and other challenging areas, “the approach was essentially to make direct contact with the traditional leaders and the religious leaders and the local actors in each of these populations. So, it’s really getting down to the grassroots level.” Infectious disease officials send teams to speak with individuals in the “local, traditional leader system.”
“Just talking to them actually got us a long way and giving them the information that they need. In most cases, I mean, people want to do things to help their kids,” said Dr. Wenger.
For now, the initial plan, per the CDC, is to “initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission” until a better supply of nOPV2 is available, then switch to IPVs.
Dr. Wenger and Dr. Wassilak report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CDC panel backs mRNA COVID vaccines over J&J because of clot risk
because the Johnson & Johnson shot carries the risk of a rare but potentially fatal side effect that causes blood clots and bleeding in the brain.
In an emergency meeting on December 16, the CDC’s Advisory Committee on Immunization Practices, or ACIP, voted unanimously (15-0) to state a preference for the mRNA vaccines over the Johnson & Johnson shot. The vote came after the panel heard a safety update on cases of thrombosis with thrombocytopenia syndrome, or TTS, a condition that causes large clots that deplete the blood of platelets, resulting in uncontrolled bleeding.
The move brings the United States in line with other wealthy countries. In May, Denmark dropped the Johnson & Johnson shot from its vaccination program because of this risk. Australia and Greece have limited the use of a similar vaccine, made by AstraZeneca, in younger people because of the TTS risk. Both vaccines use the envelope of a different kind of virus, called an adenovirus, to sneak the vaccine instructions into cells. On Dec. 16, health officials said they had determined that TTS was likely due to a class effect, meaning it happens with all adenovirus vector vaccines.
The risk of dying from TTS after a Johnson & Johnson shot is extremely rare. There is an estimated 1 death for every 2 million doses of the vaccine given in the general population. That risk is higher for women ages 30 to 49, rising to about 2 deaths for every 1 million doses given in this age group. There’s no question that the Johnson & Johnson shot has saved many more lives than it has taken, experts said
Still, the committee previously paused the use of the Johnson & Johnson vaccine in April after the first cases of TTS came to light. That pause was lifted just 10 days later, after a new warning was added to the vaccine’s label to raise awareness of the risk.
In updating the safety information on Johnson & Johnson, the panel noted that the warning label had not sufficiently lowered the risk of death from TTS. Doctors seem to be aware of the condition because none of the patients who had developed TTS had been treated with the blood thinner heparin, which can make the syndrome worse. But patients continued to die even after the label was added, the panel noted, because TTS can progress so quickly that doctors simply don’t have time to treat it.
For that reason, and because there are other, safer vaccines available, the panel decided to make what’s called a preferential statement, saying the Pfizer and Moderna mRNA vaccines should be preferred over Johnson & Johnson.
The statement leaves the J&J vaccine on the market and available to patients who are at risk of a severe allergic reaction to the mRNA vaccines. It also means that people can still choose the J&J vaccine if they still want it after being informed about the risks.
About 17 million first doses and 900,000 second doses of the Johnson & Johnson vaccine have been given in the United States. Through the end of August, 54 cases of thrombosis with thrombocytopenia syndrome (TTS) have occurred after the J&J shots in the United States. Nearly half of those were in women ages 30 to 49. There have been nine deaths from TTS after Johnson & Johnson shots.
A version of this article first appeared on WebMD.com.
because the Johnson & Johnson shot carries the risk of a rare but potentially fatal side effect that causes blood clots and bleeding in the brain.
In an emergency meeting on December 16, the CDC’s Advisory Committee on Immunization Practices, or ACIP, voted unanimously (15-0) to state a preference for the mRNA vaccines over the Johnson & Johnson shot. The vote came after the panel heard a safety update on cases of thrombosis with thrombocytopenia syndrome, or TTS, a condition that causes large clots that deplete the blood of platelets, resulting in uncontrolled bleeding.
The move brings the United States in line with other wealthy countries. In May, Denmark dropped the Johnson & Johnson shot from its vaccination program because of this risk. Australia and Greece have limited the use of a similar vaccine, made by AstraZeneca, in younger people because of the TTS risk. Both vaccines use the envelope of a different kind of virus, called an adenovirus, to sneak the vaccine instructions into cells. On Dec. 16, health officials said they had determined that TTS was likely due to a class effect, meaning it happens with all adenovirus vector vaccines.
The risk of dying from TTS after a Johnson & Johnson shot is extremely rare. There is an estimated 1 death for every 2 million doses of the vaccine given in the general population. That risk is higher for women ages 30 to 49, rising to about 2 deaths for every 1 million doses given in this age group. There’s no question that the Johnson & Johnson shot has saved many more lives than it has taken, experts said
Still, the committee previously paused the use of the Johnson & Johnson vaccine in April after the first cases of TTS came to light. That pause was lifted just 10 days later, after a new warning was added to the vaccine’s label to raise awareness of the risk.
In updating the safety information on Johnson & Johnson, the panel noted that the warning label had not sufficiently lowered the risk of death from TTS. Doctors seem to be aware of the condition because none of the patients who had developed TTS had been treated with the blood thinner heparin, which can make the syndrome worse. But patients continued to die even after the label was added, the panel noted, because TTS can progress so quickly that doctors simply don’t have time to treat it.
For that reason, and because there are other, safer vaccines available, the panel decided to make what’s called a preferential statement, saying the Pfizer and Moderna mRNA vaccines should be preferred over Johnson & Johnson.
The statement leaves the J&J vaccine on the market and available to patients who are at risk of a severe allergic reaction to the mRNA vaccines. It also means that people can still choose the J&J vaccine if they still want it after being informed about the risks.
About 17 million first doses and 900,000 second doses of the Johnson & Johnson vaccine have been given in the United States. Through the end of August, 54 cases of thrombosis with thrombocytopenia syndrome (TTS) have occurred after the J&J shots in the United States. Nearly half of those were in women ages 30 to 49. There have been nine deaths from TTS after Johnson & Johnson shots.
A version of this article first appeared on WebMD.com.
because the Johnson & Johnson shot carries the risk of a rare but potentially fatal side effect that causes blood clots and bleeding in the brain.
In an emergency meeting on December 16, the CDC’s Advisory Committee on Immunization Practices, or ACIP, voted unanimously (15-0) to state a preference for the mRNA vaccines over the Johnson & Johnson shot. The vote came after the panel heard a safety update on cases of thrombosis with thrombocytopenia syndrome, or TTS, a condition that causes large clots that deplete the blood of platelets, resulting in uncontrolled bleeding.
The move brings the United States in line with other wealthy countries. In May, Denmark dropped the Johnson & Johnson shot from its vaccination program because of this risk. Australia and Greece have limited the use of a similar vaccine, made by AstraZeneca, in younger people because of the TTS risk. Both vaccines use the envelope of a different kind of virus, called an adenovirus, to sneak the vaccine instructions into cells. On Dec. 16, health officials said they had determined that TTS was likely due to a class effect, meaning it happens with all adenovirus vector vaccines.
The risk of dying from TTS after a Johnson & Johnson shot is extremely rare. There is an estimated 1 death for every 2 million doses of the vaccine given in the general population. That risk is higher for women ages 30 to 49, rising to about 2 deaths for every 1 million doses given in this age group. There’s no question that the Johnson & Johnson shot has saved many more lives than it has taken, experts said
Still, the committee previously paused the use of the Johnson & Johnson vaccine in April after the first cases of TTS came to light. That pause was lifted just 10 days later, after a new warning was added to the vaccine’s label to raise awareness of the risk.
In updating the safety information on Johnson & Johnson, the panel noted that the warning label had not sufficiently lowered the risk of death from TTS. Doctors seem to be aware of the condition because none of the patients who had developed TTS had been treated with the blood thinner heparin, which can make the syndrome worse. But patients continued to die even after the label was added, the panel noted, because TTS can progress so quickly that doctors simply don’t have time to treat it.
For that reason, and because there are other, safer vaccines available, the panel decided to make what’s called a preferential statement, saying the Pfizer and Moderna mRNA vaccines should be preferred over Johnson & Johnson.
The statement leaves the J&J vaccine on the market and available to patients who are at risk of a severe allergic reaction to the mRNA vaccines. It also means that people can still choose the J&J vaccine if they still want it after being informed about the risks.
About 17 million first doses and 900,000 second doses of the Johnson & Johnson vaccine have been given in the United States. Through the end of August, 54 cases of thrombosis with thrombocytopenia syndrome (TTS) have occurred after the J&J shots in the United States. Nearly half of those were in women ages 30 to 49. There have been nine deaths from TTS after Johnson & Johnson shots.
A version of this article first appeared on WebMD.com.
Booster recommendations for pregnant women, teens, and other groups explained
These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.
The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.
The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.1
But what about a fourth dose? There is a possibility that some patients should be receiving one. For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series. This distinction may cause confusion for some, but is important for those immunocompromised.
Boosters in women who are pregnant
The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,2 along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.
The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.3
I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
Expanded recommendations for those aged 16-17 years
Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.
Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.1
Booster brand for those over 18 years?
Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.
The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
Take home message
Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.
References
1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.
2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.
3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.
These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.
The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.
The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.1
But what about a fourth dose? There is a possibility that some patients should be receiving one. For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series. This distinction may cause confusion for some, but is important for those immunocompromised.
Boosters in women who are pregnant
The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,2 along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.
The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.3
I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
Expanded recommendations for those aged 16-17 years
Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.
Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.1
Booster brand for those over 18 years?
Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.
The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
Take home message
Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.
References
1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.
2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.
3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.
These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.
The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.
The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.1
But what about a fourth dose? There is a possibility that some patients should be receiving one. For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series. This distinction may cause confusion for some, but is important for those immunocompromised.
Boosters in women who are pregnant
The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,2 along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.
The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.3
I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
Expanded recommendations for those aged 16-17 years
Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.
Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.1
Booster brand for those over 18 years?
Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.
The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
Take home message
Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.
Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.
References
1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.
2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.
3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.
FDA authorizes Pfizer boosters for 16- and 17-year-olds
, clearing the way for millions of teenagers to get a third dose of vaccine starting 6 months after their second dose.
The FDA said it was basing its emergency authorization of boosters for 16- and 17-year-olds on data from 200 individuals who were 18-55 years of age when they received a booster dose. They are requiring Pfizer to collect data on safety in postauthorization studies.
“The FDA has determined that the benefits of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Comirnaty outweigh the risks of myocarditis and pericarditis in individuals 16 and 17 years of age to provide continued protection against COVID-19 and the associated serious consequences that can occur including hospitalization and death,” the agency said in a news release.
Israel has been giving booster doses of Pfizer’s vaccine to everyone 12 and up since late August. Data from that country show that myocarditis cases continue to be very rare, even in younger age groups, and are mild and temporary.
The authorization comes as the effectiveness of the current vaccines against the new Omicron variant has become a point of intense scientific inquiry.
Early studies suggest that booster doses may be necessary to keep Omicron at bay, at least until new variant-specific vaccines are ready next spring.
Current evidence suggests that the protection of the vaccines is holding up well against severe disease and death, at least with Delta and early iterations of the virus.
How well they will do against Omicron, and how severe Omicron infections may be for different age groups, remain open questions.
On Dec. 8, the World Health Organization urged countries not to wait for all the science to come in, but to act now to contain any potential threat.
The first pieces of evidence on Omicron suggest that it is highly contagious, perhaps even more than Delta, though early reports suggest symptoms caused by this version of the new coronavirus may be less severe than in previous waves. Experts have cautioned that the true severity of Omicron infections isn’t yet known, since the first cases have been detected in younger people, who tend to have milder COVID-19 symptoms than those of adults and seniors.
“Vaccination and getting a booster when eligible, along with other preventive measures like masking and avoiding large crowds and poorly ventilated spaces, remain our most effective methods for fighting COVID-19,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release. “As people gather indoors with family and friends for the holidays, we can’t let up on all the preventive public health measures that we have been taking during the pandemic. With both the Delta and Omicron variants continuing to spread, vaccination remains the best protection against COVID-19.”
In mid-November, the FDA authorized boosters of the Pfizer vaccine for all individuals 18 and older, but the agency held off on expanding the use of boosters for younger age groups, partly because they have the highest risk of myocarditis, a very rare side effect.
Myocarditis cases seem to be temporary, with patients making a full recovery, though they need to be monitored in the hospital. The risk of myocarditis with a COVID-19 infection is many times higher than it is from a vaccine.
There have been little data to support the need for boosters in this age group, because children and teens tend to experience milder COVID-19 disease, though they are still at risk for post–COVID-19 complications such as long COVID and a delayed reaction to the virus called Post Acute Sequelae of SARS-CoV2 Infection among Children, or PAS-C.
All that changed with the arrival of Omicron.
A version of this article first appeared on WebMD.com.
, clearing the way for millions of teenagers to get a third dose of vaccine starting 6 months after their second dose.
The FDA said it was basing its emergency authorization of boosters for 16- and 17-year-olds on data from 200 individuals who were 18-55 years of age when they received a booster dose. They are requiring Pfizer to collect data on safety in postauthorization studies.
“The FDA has determined that the benefits of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Comirnaty outweigh the risks of myocarditis and pericarditis in individuals 16 and 17 years of age to provide continued protection against COVID-19 and the associated serious consequences that can occur including hospitalization and death,” the agency said in a news release.
Israel has been giving booster doses of Pfizer’s vaccine to everyone 12 and up since late August. Data from that country show that myocarditis cases continue to be very rare, even in younger age groups, and are mild and temporary.
The authorization comes as the effectiveness of the current vaccines against the new Omicron variant has become a point of intense scientific inquiry.
Early studies suggest that booster doses may be necessary to keep Omicron at bay, at least until new variant-specific vaccines are ready next spring.
Current evidence suggests that the protection of the vaccines is holding up well against severe disease and death, at least with Delta and early iterations of the virus.
How well they will do against Omicron, and how severe Omicron infections may be for different age groups, remain open questions.
On Dec. 8, the World Health Organization urged countries not to wait for all the science to come in, but to act now to contain any potential threat.
The first pieces of evidence on Omicron suggest that it is highly contagious, perhaps even more than Delta, though early reports suggest symptoms caused by this version of the new coronavirus may be less severe than in previous waves. Experts have cautioned that the true severity of Omicron infections isn’t yet known, since the first cases have been detected in younger people, who tend to have milder COVID-19 symptoms than those of adults and seniors.
“Vaccination and getting a booster when eligible, along with other preventive measures like masking and avoiding large crowds and poorly ventilated spaces, remain our most effective methods for fighting COVID-19,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release. “As people gather indoors with family and friends for the holidays, we can’t let up on all the preventive public health measures that we have been taking during the pandemic. With both the Delta and Omicron variants continuing to spread, vaccination remains the best protection against COVID-19.”
In mid-November, the FDA authorized boosters of the Pfizer vaccine for all individuals 18 and older, but the agency held off on expanding the use of boosters for younger age groups, partly because they have the highest risk of myocarditis, a very rare side effect.
Myocarditis cases seem to be temporary, with patients making a full recovery, though they need to be monitored in the hospital. The risk of myocarditis with a COVID-19 infection is many times higher than it is from a vaccine.
There have been little data to support the need for boosters in this age group, because children and teens tend to experience milder COVID-19 disease, though they are still at risk for post–COVID-19 complications such as long COVID and a delayed reaction to the virus called Post Acute Sequelae of SARS-CoV2 Infection among Children, or PAS-C.
All that changed with the arrival of Omicron.
A version of this article first appeared on WebMD.com.
, clearing the way for millions of teenagers to get a third dose of vaccine starting 6 months after their second dose.
The FDA said it was basing its emergency authorization of boosters for 16- and 17-year-olds on data from 200 individuals who were 18-55 years of age when they received a booster dose. They are requiring Pfizer to collect data on safety in postauthorization studies.
“The FDA has determined that the benefits of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine or Comirnaty outweigh the risks of myocarditis and pericarditis in individuals 16 and 17 years of age to provide continued protection against COVID-19 and the associated serious consequences that can occur including hospitalization and death,” the agency said in a news release.
Israel has been giving booster doses of Pfizer’s vaccine to everyone 12 and up since late August. Data from that country show that myocarditis cases continue to be very rare, even in younger age groups, and are mild and temporary.
The authorization comes as the effectiveness of the current vaccines against the new Omicron variant has become a point of intense scientific inquiry.
Early studies suggest that booster doses may be necessary to keep Omicron at bay, at least until new variant-specific vaccines are ready next spring.
Current evidence suggests that the protection of the vaccines is holding up well against severe disease and death, at least with Delta and early iterations of the virus.
How well they will do against Omicron, and how severe Omicron infections may be for different age groups, remain open questions.
On Dec. 8, the World Health Organization urged countries not to wait for all the science to come in, but to act now to contain any potential threat.
The first pieces of evidence on Omicron suggest that it is highly contagious, perhaps even more than Delta, though early reports suggest symptoms caused by this version of the new coronavirus may be less severe than in previous waves. Experts have cautioned that the true severity of Omicron infections isn’t yet known, since the first cases have been detected in younger people, who tend to have milder COVID-19 symptoms than those of adults and seniors.
“Vaccination and getting a booster when eligible, along with other preventive measures like masking and avoiding large crowds and poorly ventilated spaces, remain our most effective methods for fighting COVID-19,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release. “As people gather indoors with family and friends for the holidays, we can’t let up on all the preventive public health measures that we have been taking during the pandemic. With both the Delta and Omicron variants continuing to spread, vaccination remains the best protection against COVID-19.”
In mid-November, the FDA authorized boosters of the Pfizer vaccine for all individuals 18 and older, but the agency held off on expanding the use of boosters for younger age groups, partly because they have the highest risk of myocarditis, a very rare side effect.
Myocarditis cases seem to be temporary, with patients making a full recovery, though they need to be monitored in the hospital. The risk of myocarditis with a COVID-19 infection is many times higher than it is from a vaccine.
There have been little data to support the need for boosters in this age group, because children and teens tend to experience milder COVID-19 disease, though they are still at risk for post–COVID-19 complications such as long COVID and a delayed reaction to the virus called Post Acute Sequelae of SARS-CoV2 Infection among Children, or PAS-C.
All that changed with the arrival of Omicron.
A version of this article first appeared on WebMD.com.
Risk for severe COVID-19 and death plummets with Pfizer booster
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both studies were completed before the advent of the Omicron variant.
In one study that included data on more than 4 million patients, led by Yinon M. Bar-On, MSc, of the Weizmann Institute of Science in Rehovot, Israel, the rate of confirmed SARS-CoV-2 infection was lower in the booster group than in the nonbooster group by a factor of about 10.
This was true across all five age groups studied (range among the groups [starting with age 16], 9.0-17.2).
The risk for severe COVID-19 in the primary analysis decreased in the booster group by a factor of 17.9 (95% confidence interval, 15.1-21.2), among those aged 60 years or older. Risk for severe illness in those ages 40-59 was lower by a factor of 21.7 (95% CI, 10.6-44.2).
Among the 60 and older age group, risk for death was also reduced by a factor of 14.7 (95% CI, 10.0-21.4).
Researchers analyzed data for the period from July 30 to Oct. 10, 2021, from the Israel Ministry of Health database on 4.69 million people at least 16 years old who had received two Pfizer doses at least 5 months earlier.
In the main analysis, the researchers compared the rates of confirmed COVID-19, severe disease, and death among those who had gotten a booster at least 12 days earlier with the rates in a nonbooster group.
The authors wrote: “Booster vaccination programs may provide a way to control transmission without costly social-distancing measures and quarantines. Our findings provide evidence for the short-term effectiveness of the booster dose against the currently dominant Delta variant in persons 16 years of age or older.”
Death risk down by 90%
A second study, led by Ronen Arbel, PhD, with the community medical services division, Clalit Health Services (CHS), Tel Aviv, which included more than 800,000 participants, also found mortality risk was greatly reduced among those who received the booster compared with those who didn’t get the booster.
Participants aged 50 years or older who received a booster at least 5 months after a second Pfizer dose had 90% lower mortality risk because of COVID-19 than participants who did not get the booster.
The adjusted hazard ratio for death as a result of COVID-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% CI, 0.07-0.14; P < .001). Of the 843,208 eligible participants, 758,118 (90%) received the booster during the 54-day study period.
The study included all CHS members who were aged 50 years or older on the study start date and had received two Pfizer doses at least 5 months earlier. CHS covers about 52% of the Israeli population and is the largest of four health care organizations in Israel that provide mandatory health care.
The authors noted that, although the study period was only 54 days (Aug. 6–Sept. 29), during that time “the incidence of COVID-19 in Israel was one of the highest in the world.”
The authors of both original articles pointed out that the studies are limited by short time periods and that longer-term studies are needed to see how the booster shots stand up to known and future variants, such as Omicron.
None of the authors involved in both studies reported relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Mumps: Sometimes forgotten but not gone
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.
The 7-year-old boy sat at the edge of a stretcher in the emergency department, looking miserable, as his mother recounted his symptoms to a senior resident physician on duty. Low-grade fever, fatigue, and myalgias prompted rapid SARS-CoV-2 testing at his school. That test, as well as a repeat test at the pediatrician’s office, were negative. A triage protocol in the emergency department prompted a third test, which was also negative.
“Everyone has told me that it’s likely just a different virus,” the mother said. “But then his cheek started to swell. Have you ever seen anything like this?”
The boy turned his head, revealing a diffuse swelling that extended down his right cheek to the angle of his jaw.
“Only in textbooks,” the resident physician responded.
It is a credit to our national immunization program that most practicing clinicians have never actually seen a case of mumps. Before vaccination was introduced in 1967, infection in childhood was nearly universal. Unilateral or bilateral tender swelling of the parotid gland is the typical clinical finding. Low-grade fever, myalgias, decreased appetite, malaise, and headache may precede parotid swelling in some patients. Other patients infected with mumps may have only respiratory symptoms, and some may have no symptoms at all.
Two doses of measles-mumps-rubella vaccine have been recommended for children in the United States since 1989, with the first dose administered at 12-15 months of age. According to data collected through the National Immunization Survey, more than 92% of children in the United States receive at least one dose of measles-mumps-rubella vaccine by 24 months of age. The vaccine is immunogenic, with 94% of recipients developing measurable mumps antibody (range, 89%-97%). The vaccine has been a public health success: Overall, mumps cases declined more than 99% between 1967 and 2005.
But in the mid-2000s, mumps cases started to rise again, with more than 28,000 reported between 2007 and 2019. Annual cases ranged from 229 to 6,369 and while large, localized outbreaks have contributed to peak years, mumps has been reported from all 50 states and the District of Columbia. According to a recently published paper in Pediatrics, nearly a third of these cases occurred in children <18 years of age and most had been appropriately immunized for age.
Of the 9,172 cases reported in children, 5,461 or 60% occurred between 2015 and 2019. Of these, 55% were in boys. While cases occurred in children of all ages, 54% were in children 11-17 years of age, and 33% were in children 5-10 years of age. Non-Hispanic Asian and/or Pacific Islander children accounted for 38% of cases. Only 2% of cases were associated with international travel and were presumed to have been acquired outside the United States
The reason for the increase in mumps cases in recent years is not well understood. Outbreaks in fully immunized college students have prompted concern about poor B-cell memory after vaccination resulting in waning immunity over time. In the past, antibodies against mumps were boosted by exposure to wild-type mumps virus but such exposures have become fortunately rare for most of us. Cases in recently immunized children suggest there is more to the story. Notably, there is a mismatch between the genotype A mumps virus contained in the current MMR and MMRV vaccines and the genotype G virus currently circulating in the United States.
With the onset of the pandemic and implementation of mitigation measures to prevent the spread of COVID-19, circulation of some common respiratory viruses, including respiratory syncytial virus and influenza, was sharply curtailed. Mumps continued to circulate, albeit at reduced levels, with 616 cases reported in 2020. In 2021, 30 states and jurisdictions reported 139 cases through Dec. 1.
Clinicians should suspect mumps in all cases of parotitis, regardless of an individual’s age, vaccination status, or travel history. Laboratory testing is required to distinguish mumps from other infectious and noninfectious causes of parotitis. Infectious causes include gram-positive and gram-negative bacterial infection, as well as other viral infections, including Epstein-Barr virus, coxsackie viruses, parainfluenza, and rarely, influenza. Case reports also describe parotitis coincident with SARS-CoV-2 infection.
When parotitis has been present for 3 days or less, a buccal swab for RT-PCR should be obtained, massaging the parotid gland for 30 seconds before specimen collection. When parotitis has been present for >3 days, a mumps Immunoglobulin M serum antibody should be collected in addition to the buccal swab PCR. A negative IgM does not exclude the possibility of infection, especially in immunized individuals. Mumps is a nationally notifiable disease, and all confirmed and suspect cases should be reported to the state or local health department.
Back in the emergency department, the mother was counseled about the potential diagnosis of mumps and the need for her son to isolate at home for 5 days after the onset of the parotid swelling. She was also educated about potential complications of mumps, including orchitis, aseptic meningitis and encephalitis, and hearing loss. Fortunately, complications are less common in individuals who have been immunized, and orchitis rarely occurs in prepubertal boys.
The resident physician also confirmed that other members of the household had been appropriately immunized for age. While the MMR vaccine does not prevent illness in those already infected with mumps and is not indicated as postexposure prophylaxis, providing vaccine to those not already immunized can protect against future exposures. A third dose of MMR vaccine is only indicated in the setting of an outbreak and when specifically recommended by public health authorities for those deemed to be in a high-risk group. Additional information about mumps is available at www.cdc.gov/mumps/hcp.html#report.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.
Vaccine protection drops against Omicron, making boosters crucial
A raft of new
The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.
But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.
“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.”
Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.
President Biden hailed the study results as good news.
“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
More research needed
Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.
Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.
The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.
She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.
“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.
Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.
Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.
She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.
“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
Retool the vaccines?
Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.
“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.
Dr. Palese said he was definitely concerned about a possible Omicron wave.
“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.
“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”
Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.
“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.
“We can prevent Omicron [from] becoming a global crisis right now,” he said.
A version of this article first appeared on Medscape.com.
A raft of new
The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.
But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.
“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.”
Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.
President Biden hailed the study results as good news.
“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
More research needed
Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.
Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.
The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.
She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.
“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.
Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.
Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.
She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.
“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
Retool the vaccines?
Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.
“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.
Dr. Palese said he was definitely concerned about a possible Omicron wave.
“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.
“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”
Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.
“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.
“We can prevent Omicron [from] becoming a global crisis right now,” he said.
A version of this article first appeared on Medscape.com.
A raft of new
The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.
But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.
“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.”
Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.
President Biden hailed the study results as good news.
“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
More research needed
Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.
Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.
The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.
She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.
“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.
Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.
Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.
She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.
“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
Retool the vaccines?
Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.
“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.
Dr. Palese said he was definitely concerned about a possible Omicron wave.
“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.
“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”
Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.
“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.
“We can prevent Omicron [from] becoming a global crisis right now,” he said.
A version of this article first appeared on Medscape.com.
Despite ‘getting it wrong’ we must continue to do what’s right
I have been wrong about the COVID-19 pandemic any number of times. During the early days of the pandemic, a colleague asked me if he should book his airline ticket to Chicago for our annual Essential Evidence conference. I told him to go ahead. The country shut down the next week.
In September of this year, I was ready to book my flight to Phoenix for a presentation at the Arizona Academy of Family Physicians annual meeting. I thought COVID-19 activity was winding down. I was wrong again. The conference was changed to virtual presentations.
And now, as I write this editorial late in November, I find myself wrong a third time. I figured the smoldering COVID-19 activity in Michigan, where I live, would wind down before Thanksgiving. But it is expanding wildly throughout the Midwest.
Wrong again, and again.
I figured most everyone would be vaccinated as soon as vaccines were available, given the dangerous nature of the virus and the benign nature of the vaccines. But here we are, more than 750,000 deaths later and, as a country, we still have not learned our lesson. I won’t get into the disinformation campaign against the existence of the pandemic and the effectiveness and safety of the vaccines; this disinformation campaign seems to be designed to kill as many Americans as possible.
The COVID-19 epidemic is personal for all of us. Not one of us has been immune to its effects. All of us have had a relative or friend die of COVID-19 infection. All of us have had to wear masks and be cautious about contacts with others. All of us have cancelled or restricted travel. My wife and I are debating whether or not we should gather for the holidays with our children and grandchildren in Michigan, despite the fact that all of us have been immunized. One of my sons has a mother-in-law with pulmonary fibrosis; he and his family will all be doing home testing for COVID-19 the day before visiting her.
When will this nightmare end? There is no question that everyone in the United States—and most likely, the entire world—will eventually get vaccinated against COVID-19 or get infected with it. We must continue urging everyone to make the smart, safe choice and get vaccinated.
There are still hundreds of thousands of lives to be saved.
I have been wrong about the COVID-19 pandemic any number of times. During the early days of the pandemic, a colleague asked me if he should book his airline ticket to Chicago for our annual Essential Evidence conference. I told him to go ahead. The country shut down the next week.
In September of this year, I was ready to book my flight to Phoenix for a presentation at the Arizona Academy of Family Physicians annual meeting. I thought COVID-19 activity was winding down. I was wrong again. The conference was changed to virtual presentations.
And now, as I write this editorial late in November, I find myself wrong a third time. I figured the smoldering COVID-19 activity in Michigan, where I live, would wind down before Thanksgiving. But it is expanding wildly throughout the Midwest.
Wrong again, and again.
I figured most everyone would be vaccinated as soon as vaccines were available, given the dangerous nature of the virus and the benign nature of the vaccines. But here we are, more than 750,000 deaths later and, as a country, we still have not learned our lesson. I won’t get into the disinformation campaign against the existence of the pandemic and the effectiveness and safety of the vaccines; this disinformation campaign seems to be designed to kill as many Americans as possible.
The COVID-19 epidemic is personal for all of us. Not one of us has been immune to its effects. All of us have had a relative or friend die of COVID-19 infection. All of us have had to wear masks and be cautious about contacts with others. All of us have cancelled or restricted travel. My wife and I are debating whether or not we should gather for the holidays with our children and grandchildren in Michigan, despite the fact that all of us have been immunized. One of my sons has a mother-in-law with pulmonary fibrosis; he and his family will all be doing home testing for COVID-19 the day before visiting her.
When will this nightmare end? There is no question that everyone in the United States—and most likely, the entire world—will eventually get vaccinated against COVID-19 or get infected with it. We must continue urging everyone to make the smart, safe choice and get vaccinated.
There are still hundreds of thousands of lives to be saved.
I have been wrong about the COVID-19 pandemic any number of times. During the early days of the pandemic, a colleague asked me if he should book his airline ticket to Chicago for our annual Essential Evidence conference. I told him to go ahead. The country shut down the next week.
In September of this year, I was ready to book my flight to Phoenix for a presentation at the Arizona Academy of Family Physicians annual meeting. I thought COVID-19 activity was winding down. I was wrong again. The conference was changed to virtual presentations.
And now, as I write this editorial late in November, I find myself wrong a third time. I figured the smoldering COVID-19 activity in Michigan, where I live, would wind down before Thanksgiving. But it is expanding wildly throughout the Midwest.
Wrong again, and again.
I figured most everyone would be vaccinated as soon as vaccines were available, given the dangerous nature of the virus and the benign nature of the vaccines. But here we are, more than 750,000 deaths later and, as a country, we still have not learned our lesson. I won’t get into the disinformation campaign against the existence of the pandemic and the effectiveness and safety of the vaccines; this disinformation campaign seems to be designed to kill as many Americans as possible.
The COVID-19 epidemic is personal for all of us. Not one of us has been immune to its effects. All of us have had a relative or friend die of COVID-19 infection. All of us have had to wear masks and be cautious about contacts with others. All of us have cancelled or restricted travel. My wife and I are debating whether or not we should gather for the holidays with our children and grandchildren in Michigan, despite the fact that all of us have been immunized. One of my sons has a mother-in-law with pulmonary fibrosis; he and his family will all be doing home testing for COVID-19 the day before visiting her.
When will this nightmare end? There is no question that everyone in the United States—and most likely, the entire world—will eventually get vaccinated against COVID-19 or get infected with it. We must continue urging everyone to make the smart, safe choice and get vaccinated.
There are still hundreds of thousands of lives to be saved.
Cervical cancer update: The latest on screening & management
The World Health Organization estimates that, in 2020, worldwide, there were 604,000 new cases of uterine cervical cancer and approximately 342,000 deaths, 84% of which occurred in developing countries.1 In the United States, as of 2018, the lifetime risk of death from cervical cancer was 2.2 for every 100,000
In this article, we summarize recent updates in the epidemiology, prevention, and treatment of cervical cancer. We emphasize recent information of value to family physicians, including updates in clinical guidelines and other pertinent national recommendations.
Spotlight continues to shine on HPV
It has been known for several decades that cervical cancer is caused by human papillomavirus (HPV). Of more than 100 known HPV types, 14 or 15 are classified as carcinogenic. HPV 16 is the most common oncogenic type, causing more than 60% of cases of cervical cancer3,4
HPV is the most common sexually transmitted infection, with as many as 80% of sexually active people becoming infected during their lifetime, generally before 50 years of age.5 HPV also causes other anogenital and oropharyngeal cancers; however, worldwide, more than 80% of HPV-associated cancers are cervical.6 Risk factors for cervical cancer are listed in TABLE 1.7 Cervical cancer is less common when partners are circumcised.7
Most cases of HPV infection clear in 1 or 2 years
At least 70% of cervical cancers are squamous cell carcinoma (SCC); 20% to 25% are adenocarcinoma (ADC); and < 3% to 5% are adenosquamous carcinoma.10 Almost 100% of cervical SCCs are HPV+, as are 86% of cervical ADCs. The most common reason for HPV-negative status in patients with cervical cancer is false-negative testing because of inadequate methods.
Primary prevention through vaccination
HPV vaccination was introduced in 2006 in the United States for girls,a and for boysa in 2011. The primary reason for vaccinating boys is to reduce the rates of HPV-related anal and oropharyngeal cancer. The only available HPV vaccine in the United States is Gardasil 9 (9-valent vaccine, recombinant; Merck), which provides coverage for 7 high-risk HPV types that account for approximately 90% of cervical cancers and 2 types (6 and 11) that are the principal causes of condylomata acuminata (genital warts). Future generations of prophylactic vaccines are expected to cover additional strains.
Continue to: Vaccine studies...
Vaccine studies have been summarized in a Cochrane review,11 showing that vaccination is highly effective for prevention of cervical dysplasia, especially when given to young girls and womena previously unexposed to the virus. It has not been fully established how long protection lasts, but vaccination appears to be 70% to 90% effective for ≥ 10 years.
Dosing schedule. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends a 2-dose schedule 6 to 15 months apart, for both girls and boys between 9 and 14 years of age.12 A third dose is indicated if the first and second doses were given less than 5 months apart, or the person is older than 15 years or is immunocompromised. No recommendation has been made for revaccination after the primary series.
In 2018, the US Food and Drug Administration approved Gardasil 9 for adults 27 to 45 years of age. In June 2019, ACIP recommended vaccination for mena as old as 26 years, and adopted a recommendation that unvaccinated men and women between 27 and 45 years discuss HPV vaccination with their physician.13
The adolescent HPV vaccination rate varies by state; however, all states lag behind the CDC’s Healthy People 2020 goal of 80%.14 Barriers to vaccination include cost, infrastructure limitations, and social stigma.
Secondary prevention: Screening and Tx of precancerous lesions
Cervical cancer screening identifies patients at increased risk of cervical cancer and reassures the great majority of them that their risk of cervical cancer is very low. There are 3 general approaches to cervical cancer screening:
- cytology-based screening, which has been implemented for decades in many countries
- primary testing for DNA or RNA markers of high-risk HPV types
- co-testing with cytology-based screening plus HPV testing.
Continue to: USPSTF guidance
USPSTF guidance. Recommendations of the US Preventive Services Task Force (USPSTF) for cervical cancer screening were updated in 2018 (TABLE 215). The recommendations state that high-risk HPV screening alone is a strategy that is amenable to patient self-sampling and self-mailing for processing—a protocol that has the potential to improve access
ASCCP guidance. The American Society of Colposcopy and Cervical Pathology (ASCCP) makes nearly the same recommendations for cervical cancer screening. An exception is that ASCCP guidelines allow for the possibility of screening using primary high-risk HPV testing for patients starting at 25 years of age.16
Screening programs that can be initiated at a later age and longer intervals should be possible once the adolescent vaccination rate is optimized and vaccination registries are widely implemented.
Cervical cytology protocol
Cervical cytologic abnormalities are reported using the Bethesda system. Specimen adequacy is the most important component of quality assurance,17 and is determined primarily by sufficient cellularity. However, any specimen containing abnormal squamous cells of undetermined significance (ASCUS) or atypical glandular cells (AGCs) is considered satisfactory, regardless of the number of cells. Obscuring factors that impair quality include excessive blood; inflammation; air-drying artifact; and an interfering substance, such as lubricant. The presence of reactive changes resulting from inflammation does not require further evaluation unless the patient is immunosuppressed.
Abnormalities are most often of squamous cells, of 2 categories: low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). HSILs are more likely to be associated with persistent HPV infection and higher risk of progression to cervical cancer.
Continue to: Cytologic findings...
Cytologic findings can be associated with histologic findings that are sometimes more, sometimes less, severe. LSIL cytology specimens that contain a few cells that are suspicious for HSIL, but that do not contain enough cells to be diagnostic, are reported as atypical squamous cells, and do not exclude a high-grade intraepithelial lesion.
Glandular-cell abnormalities usually originate from the glandular epithelium of the endocervix or the endometrium—most often, AGCs. Less frequent are AGCs, favor neoplasia; endocervical adenocarcinoma in situ; and ADC. Rarely, AGCs are associated with adenosquamous carcinoma. Endometrial polyps are a typical benign pathology that can be associated with AGCs.
In about 30% of cases, AGCs are associated with premalignant or malignant disease.18 The risk of malignancy in patients with AGCs increases with age, from < 2% among patients younger than 40 years to approximately 15% among those > 50 years.19 Endometrial malignancy is more common than cervical malignancy among patients > 40 years.
AGC cytology requires endocervical curettage, plus endometrial sampling for patients ≥ 35 years
Cytology-based screening has limitations. Sensitivity is relatively low and dependent on the expertise of the cytologist, although regular repeat testing has been used to overcome this limitation. A substantial subset of results are reported as equivocal—ie, ASCUS.
Continue to: Primary HPV screening
Primary HPV screening
Primary HPV testing was approved by the US Food and Drug Administration in 2015 and recommended as an appropriate screening option by professional societies
In contrast to cytology-based screening, HPV testing has high sensitivity (≥ 90%); the population-based negative likelihood ratio is near zero.20 This degree of sensitivity allows for extended screening intervals. However, primary HPV testing lacks specificity for persistent infection and high-grade or invasive lesions, which approximately doubles the number of patients who screen positive. The potential for excess patients to be referred for colposcopy led to the need for secondary triage.
Instituting secondary triage. Cytology is, currently, the primary method of secondary triage, reducing the number of referrals for colposcopy by nearly one-half, compared to referrals for all high-risk HPV results, and with better overall accuracy over cytology with high-risk HPV triage.21 When cytology shows ASCUS, or worse, refer the patient for colposcopy; alternatively, if so-called reflex testing for HPV types 16 and 18 is available and positive, direct referral to colposcopy without cytology is also appropriate.
In the future, secondary triage for cytology is likely to be replaced with improved technologies, such as immunostaining of the specimen for biomarkers associated with cervical precancer or cancer, or for viral genome methylation testing.22
Management of abnormal cervical cancer screening results
Routine screening applies to asymptomatic patients who do not require surveillance because they have not had prior abnormal screening results. In 2020, ASCCP published risk-based management consensus guidelines that were developed for abnormal cervical cancer screening tests and for cancer precursors.16 Guiding principles, and screening situations in which the guidelines can be applied, are summarized in TABLE 3
Continue to: ASCCP guidelines...
ASCCP guidelines provide a framework to incorporate new data and technologies without major revision
Some noteworthy scenarios in ASCCP risk-based management are:
- For unsatisfactory cytology with a negative HPV test or no HPV test, repeat age-based screening in 2 to 4 months. (Note: A negative HPV test might reflect an inadequate specimen; do not interpret this result as a true negative.)
- An absent transformation zone (ie, between glandular and squamous cervical cells) with an otherwise adequate specimen should be interpreted as satisfactory for screening in patients 21 to 29 years of age. For those ≥ 30 years and with no HPV testing in this circumstance, HPV testing is preferred; repeating cytology, in 3 years, is also acceptable.
- After a finding of LSIL/CIN1 without evidence of a high-grade abnormality, and after 2 negative annual screenings (including HPV testing), a return to 3-year (not 5-year) screening is recommended.
- A cytology result of an HSIL carries a risk of 26% for CIN3+, in which case colposcopy is recommended, regardless of HPV test results.
- For long-term management after treatment for CIN2+, continue surveillance testing every 3 years after 3 consecutive negative HPV tests or cytology findings, for at least 25 years. If the 25-year threshold is reached before 65 years of age, continuing surveillance every 3 years is optional, as long as the patient is in good health (ie, life expectancy ≥ 10 years).
- After hysterectomy for a high-grade abnormality, annual vaginal HPV testing is recommended until 3 negative tests are returned; after that, surveillance shifts to a 3-year interval until the 25-year threshold.
Treatment of cancer precursors
Treatment for cervical dysplasia is excisional or ablative.
Excisional therapy. In most cases, excisional therapy (either a loop electrosurgical excision procedure [LEEP; also known as large loop excision of the transformation zone, cold knife conization, and laser conization] or cone biopsy) is required, or preferred. Excisional treatment has the advantage of providing a diagnostic specimen.
The World Health Organization recommends LEEP over ablation in settings in which LEEP is available.23 ASCCP states that, in the relatively few cases in which treatment is needed and it is for CIN1, either excision or ablation is acceptable. TABLE 416 lists situations in which excisional treatment is required because a diagnostic specimen is needed.
Continue to: Ablative treatments
Ablative treatments are cryotherapy, CO2 laser ablation, and thermal ablation. Ablative therapy has the advantage of presenting less risk of adverse obstetric outcomes (eg, preterm birth); it can be used if the indication for therapy is:
- CIN1 or CIN2 and HPV type 16 or 18 positivity
- concordant cytology and histology
- satisfactory colposcopy
- negative endocervical curettage.
The most common ablative treatment is liquid nitrogen applied to a metal tip under local anesthesia.
Hysterectomy can be considered for patients with recurrent CIN2+ who have completed childbearing or for whom repeat excision is infeasible (eg, scarring or a short cervix), or both.
Cost, availability, and convenience might play a role in decision-making with regard to the treatment choice for cancer precursors.
Is care after treatment called for? Patients who continue to be at increased risk of (and thus mortality from) cervical and vaginal cancer require enhanced surveillance. The risk of cancer is more than triple for patients who were given their diagnosis, and treated, when they were > 60 years, compared to patients treated in their 30s.1 The excess period of risk covers at least 25 years after treatment, even among patients who have had 3 posttreatment screenings.
Continue to: Persistent HPV positivity...
Persistent HPV positivity is more challenging. Patients infected with HPV type 16 have an increased risk of residual disease.
Cancer management
Invasive cancer. Most cervical cancers (60%) occur among patients who have not been screened during the 5 years before their diagnosis.24 For patients who have a diagnosis of cancer, those detected through screening have a much better prognosis than those identified by symptoms (mean cure rate, 92% and 66%, respectively).25 The median 5-year survival for patients who were not screened during the 5 years before their diagnosis of cervical cancer is 66%.2
In unscreened patients, cervical cancer usually manifests as abnormal vaginal bleeding, especially postcoitally. In approximately 45% of cases, the patient has localized disease at diagnosis; in 36%, regional disease; and in 15%, distant metastases.26
For cancers marked by stromal invasion < 3 mm, appropriate treatment is cone biopsy or simple hysterectomy.27
Most patients with early-stage cervical cancer undergo modified radical hysterectomy. The ovaries are usually conserved, unless the cancer is adenocarcinoma. Sentinel-node dissection has become standard practice. Primary radiation therapy is most often used for patients who are a poor surgical candidate because of medical comorbidity or poor functional status. Antiangiogenic agents (eg, bevacizumab) can be used as adjuvant palliative therapy for advanced and recurrent disease
Continue to: After treatment for...
After treatment for invasive cervical cancer, the goal is early detection of recurrence, although there is no consensus on a protocol. Most recurrences are detected within the first 2 years.
Long-term sequelae after treatment for advanced cancer are considerable. Patients report significantly lower quality of life,
Hormone replacement therapy is generally considered acceptable after treatment of cervical cancer because it does not increase replication of HPV.
Recurrent or metastatic cancer. Recurrence or metastases will develop in 15% to 60% of patients,30 usually within the first 2 years after treatment.
Management depends on location and extent of disease, using mainly radiation therapy or surgical resection. Recurrence or metastasis is usually incurable.
Continue to: Last, there are promising...
Last, there are promising areas of research for more effective treatment for cervical cancer precursors and cancers, including gene editing tools31 and therapeutic
Prospects for better cervical cancer care
Prevention. HPV vaccination is likely to have a large impact on population-based risk of both cancer and cancer precursors in the next generation.
Screening in the foreseeable future will gravitate toward reliance on primary HPV screening, with a self-sampling option.
Surveillance after dysplastic disease. The 2019 ASCCP guidelines for surveillance and intervention decisions after abnormal cancer screening results will evolve to incorporate introduction of new technology into computerized algorithms.
Treatment. New biologic therapies, including monoclonal antibodies and therapeutic vaccines against HPV, will likely be introduced for treating cancer precursors and invasive cancer.
A NOTE FROM THE EDITORS The Editors of The Journal of Family Practice recognize the importance of addressing the reproductive health of gender-diverse individuals. In this article, we use the words “women,” “men,” “girls,” and “boys” in limited circumstances (1) for ease of reading and (2) to reflect the official language of the US Food and Drug Administration and the Advisory Committee on Immunization Practices. The reader should consider the information and guidance offered in this discussion of cervical cancer and other human papillomavirus-related cancers to speak to the care of people with a uterine cervix and people with a penis.
CORRESPONDENCE
Linda Speer, MD, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; Linda.speer@utoledo.edu
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. doi: 10.3322/caac.21660
2. Cancer stat facts: cervical cancer. National Cancer Institute Surveillance, Epidemiology, and End Results [SEER] Program. Accessed November 14, 2021. https://seer.cancer.gov/statfacts/html/cervix.html
3. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131:2349-2359. doi: 10.1002/ijc.27485
4. Winer RL, Hughes JP, Feng Q, et al. Early history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev. 2011;20:699-707. doi: 10.1158/1055-9965.EPI-10-1108
5. Chesson HW, Dunne EF, Hariri F, et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014;41:660-664. doi: 10.1097/OLQ.0000000000000193
6. Human papillomavirus (HPV) and cervical cancer. Fact sheet. Geneva, Switzerland: World Health Organization; November 11, 2020. Accessed November 14, 2021. www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer
7. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007;120:885-891. doi: 10.1002/ijc.22357
8. McCredie MRE, Sharples KJ, Paul C, et al. Natural history of cervical cancer neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008:9:425-434. doi: 10.1016/S1470-2045(08)70103-7
9. de Sanjose S, Quint WG, Alemany I, et al; . Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective, cross-sectional worldwide study. Lancet Oncol. 2010;11:1048-1056. doi: 10.1016/S1470-2045(10)70230-8
10. Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review 1975-2004. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2004/#citation
11. Arbyn M, Xu L, Simoens C, et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5:CD009069. doi: 10.1002/14651858.CD009069.pub3
12. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016:65;1405-1408. doi: 10.15585/mmwr.mm6549a5
13. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702. doi: 10.15585/mmwr.mm6832a3
14. State-level data: Female adolescents receiving 2 or 3 doses of HPV vaccine by age 13-15 years (percent). HealthyPeople.gov. Accessed November 14, 2021. www.healthypeople.gov/2020/data/map/4657?year=2018
15. United States Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;320:674-686. doi: 10.1001/jama.2018.10897
16. Perkins RB, Guido RS, Castle PE, et al; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2020;24:102-131. doi: 10.1097/LGT.0000000000000525
17. Nayar R, Wilbur DC. The Pap test and Bethesda 2014. Cancer Cytopathol. 2015;123;271-281. doi: 10.1002/cncy.21521
18. Schnatz PF, Guile M, O’Sullivan DM, et al. Clinical significance of atypical glandular cells on cervical cytology. Obstet Gynecol 2006;107:701-708. doi: 10.1097/01.AOG.0000202401.29145.68
19. Zhao C, Florea A, Onisko A, et al. Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: results from a large academic womens hospital laboratory employing sensitive screening methods. Gynecol Oncol 2009;114:383-389. doi: 10.1016/j.ygyno.2009.05.019
20. Zazove P, Reed BD, Gregoire L, et al. Low false-negative rate of PCR analysis for detecting human papillomavirus-related cervical lesions. J Clin Microbiol. 1998;36:2708-2713. doi: 10.1128/JCM.36.9.2708-2713.1998
21. Richardson LA, El-Zein M, Ramankumar AV, et al; . HPV DNA testing with cytology triage in cervical cancer screening: influence of revealing HPV infection status. Cancer Cytopathol. 2015:123:745-754. doi: 10.1002/cncy.21596
22. Wentzensen N, Schiffman M, Palmer T, et al. Triage of HPV positive women in cervical cancer screening. J Clin Virol 2016;76:S49-S55. doi: 10.1016/j.jcv.2015.11.015
23. WHO Guidelines: Use of Cryotherapy for Cervical Intraepithelial Neoplasia. Geneva, Switzerland: World Health Organization; 2011. Accessed November 14, 2021. www.ncbi.nlm.nih.gov/books/NBK138476/pdf/Bookshelf_NBK138476.pdf
24. Spence AR, Goggin P, Franco EL. Process of care failures in invasive cervical cancer: systematic review and meta-analysis. Prev Med. 2007:45:93-106. doi: 10.1016/j.ypmed.2007.06.007
25. Rositch AF, Nowak RG, Gravitt PE. Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000-2009. Cancer. 2014:120:2032-2038. doi: 10.1002/cncr.28548
26. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA: Cancer J Clin. 2021;71:7-33. doi: 10.3322/caac.21654
27. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: cervical cancer. Accessed June 15, 2021. www.nccn.org/professionals/physician_gls/pdf/cervical.pdf
28. Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390:1654-1663. doi: 10.1016/S0140-6736(17)31607-0
29. Osann K, Hsieh S, Nelson EL, et al. Factors associated with poor quality of life among cervical cancer survivors: implications for clinical care and clinical trials. Gynecol Oncol. 2014;135:266-272. doi: 10.1016/j.ygyno.2014.08.036
30. Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975 to 2003. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2003/#citation
31. Hu Z, Ding M. The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications. Cancer Med. 2018;7:5217-5236. doi: 10.1002/cam4.1501
32. Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: opportunity and challenge. Cancer Lett. 2020;471:88-102. doi: 10.1016/j.canlet.2019.11.039
The World Health Organization estimates that, in 2020, worldwide, there were 604,000 new cases of uterine cervical cancer and approximately 342,000 deaths, 84% of which occurred in developing countries.1 In the United States, as of 2018, the lifetime risk of death from cervical cancer was 2.2 for every 100,000
In this article, we summarize recent updates in the epidemiology, prevention, and treatment of cervical cancer. We emphasize recent information of value to family physicians, including updates in clinical guidelines and other pertinent national recommendations.
Spotlight continues to shine on HPV
It has been known for several decades that cervical cancer is caused by human papillomavirus (HPV). Of more than 100 known HPV types, 14 or 15 are classified as carcinogenic. HPV 16 is the most common oncogenic type, causing more than 60% of cases of cervical cancer3,4
HPV is the most common sexually transmitted infection, with as many as 80% of sexually active people becoming infected during their lifetime, generally before 50 years of age.5 HPV also causes other anogenital and oropharyngeal cancers; however, worldwide, more than 80% of HPV-associated cancers are cervical.6 Risk factors for cervical cancer are listed in TABLE 1.7 Cervical cancer is less common when partners are circumcised.7
Most cases of HPV infection clear in 1 or 2 years
At least 70% of cervical cancers are squamous cell carcinoma (SCC); 20% to 25% are adenocarcinoma (ADC); and < 3% to 5% are adenosquamous carcinoma.10 Almost 100% of cervical SCCs are HPV+, as are 86% of cervical ADCs. The most common reason for HPV-negative status in patients with cervical cancer is false-negative testing because of inadequate methods.
Primary prevention through vaccination
HPV vaccination was introduced in 2006 in the United States for girls,a and for boysa in 2011. The primary reason for vaccinating boys is to reduce the rates of HPV-related anal and oropharyngeal cancer. The only available HPV vaccine in the United States is Gardasil 9 (9-valent vaccine, recombinant; Merck), which provides coverage for 7 high-risk HPV types that account for approximately 90% of cervical cancers and 2 types (6 and 11) that are the principal causes of condylomata acuminata (genital warts). Future generations of prophylactic vaccines are expected to cover additional strains.
Continue to: Vaccine studies...
Vaccine studies have been summarized in a Cochrane review,11 showing that vaccination is highly effective for prevention of cervical dysplasia, especially when given to young girls and womena previously unexposed to the virus. It has not been fully established how long protection lasts, but vaccination appears to be 70% to 90% effective for ≥ 10 years.
Dosing schedule. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends a 2-dose schedule 6 to 15 months apart, for both girls and boys between 9 and 14 years of age.12 A third dose is indicated if the first and second doses were given less than 5 months apart, or the person is older than 15 years or is immunocompromised. No recommendation has been made for revaccination after the primary series.
In 2018, the US Food and Drug Administration approved Gardasil 9 for adults 27 to 45 years of age. In June 2019, ACIP recommended vaccination for mena as old as 26 years, and adopted a recommendation that unvaccinated men and women between 27 and 45 years discuss HPV vaccination with their physician.13
The adolescent HPV vaccination rate varies by state; however, all states lag behind the CDC’s Healthy People 2020 goal of 80%.14 Barriers to vaccination include cost, infrastructure limitations, and social stigma.
Secondary prevention: Screening and Tx of precancerous lesions
Cervical cancer screening identifies patients at increased risk of cervical cancer and reassures the great majority of them that their risk of cervical cancer is very low. There are 3 general approaches to cervical cancer screening:
- cytology-based screening, which has been implemented for decades in many countries
- primary testing for DNA or RNA markers of high-risk HPV types
- co-testing with cytology-based screening plus HPV testing.
Continue to: USPSTF guidance
USPSTF guidance. Recommendations of the US Preventive Services Task Force (USPSTF) for cervical cancer screening were updated in 2018 (TABLE 215). The recommendations state that high-risk HPV screening alone is a strategy that is amenable to patient self-sampling and self-mailing for processing—a protocol that has the potential to improve access
ASCCP guidance. The American Society of Colposcopy and Cervical Pathology (ASCCP) makes nearly the same recommendations for cervical cancer screening. An exception is that ASCCP guidelines allow for the possibility of screening using primary high-risk HPV testing for patients starting at 25 years of age.16
Screening programs that can be initiated at a later age and longer intervals should be possible once the adolescent vaccination rate is optimized and vaccination registries are widely implemented.
Cervical cytology protocol
Cervical cytologic abnormalities are reported using the Bethesda system. Specimen adequacy is the most important component of quality assurance,17 and is determined primarily by sufficient cellularity. However, any specimen containing abnormal squamous cells of undetermined significance (ASCUS) or atypical glandular cells (AGCs) is considered satisfactory, regardless of the number of cells. Obscuring factors that impair quality include excessive blood; inflammation; air-drying artifact; and an interfering substance, such as lubricant. The presence of reactive changes resulting from inflammation does not require further evaluation unless the patient is immunosuppressed.
Abnormalities are most often of squamous cells, of 2 categories: low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). HSILs are more likely to be associated with persistent HPV infection and higher risk of progression to cervical cancer.
Continue to: Cytologic findings...
Cytologic findings can be associated with histologic findings that are sometimes more, sometimes less, severe. LSIL cytology specimens that contain a few cells that are suspicious for HSIL, but that do not contain enough cells to be diagnostic, are reported as atypical squamous cells, and do not exclude a high-grade intraepithelial lesion.
Glandular-cell abnormalities usually originate from the glandular epithelium of the endocervix or the endometrium—most often, AGCs. Less frequent are AGCs, favor neoplasia; endocervical adenocarcinoma in situ; and ADC. Rarely, AGCs are associated with adenosquamous carcinoma. Endometrial polyps are a typical benign pathology that can be associated with AGCs.
In about 30% of cases, AGCs are associated with premalignant or malignant disease.18 The risk of malignancy in patients with AGCs increases with age, from < 2% among patients younger than 40 years to approximately 15% among those > 50 years.19 Endometrial malignancy is more common than cervical malignancy among patients > 40 years.
AGC cytology requires endocervical curettage, plus endometrial sampling for patients ≥ 35 years
Cytology-based screening has limitations. Sensitivity is relatively low and dependent on the expertise of the cytologist, although regular repeat testing has been used to overcome this limitation. A substantial subset of results are reported as equivocal—ie, ASCUS.
Continue to: Primary HPV screening
Primary HPV screening
Primary HPV testing was approved by the US Food and Drug Administration in 2015 and recommended as an appropriate screening option by professional societies
In contrast to cytology-based screening, HPV testing has high sensitivity (≥ 90%); the population-based negative likelihood ratio is near zero.20 This degree of sensitivity allows for extended screening intervals. However, primary HPV testing lacks specificity for persistent infection and high-grade or invasive lesions, which approximately doubles the number of patients who screen positive. The potential for excess patients to be referred for colposcopy led to the need for secondary triage.
Instituting secondary triage. Cytology is, currently, the primary method of secondary triage, reducing the number of referrals for colposcopy by nearly one-half, compared to referrals for all high-risk HPV results, and with better overall accuracy over cytology with high-risk HPV triage.21 When cytology shows ASCUS, or worse, refer the patient for colposcopy; alternatively, if so-called reflex testing for HPV types 16 and 18 is available and positive, direct referral to colposcopy without cytology is also appropriate.
In the future, secondary triage for cytology is likely to be replaced with improved technologies, such as immunostaining of the specimen for biomarkers associated with cervical precancer or cancer, or for viral genome methylation testing.22
Management of abnormal cervical cancer screening results
Routine screening applies to asymptomatic patients who do not require surveillance because they have not had prior abnormal screening results. In 2020, ASCCP published risk-based management consensus guidelines that were developed for abnormal cervical cancer screening tests and for cancer precursors.16 Guiding principles, and screening situations in which the guidelines can be applied, are summarized in TABLE 3
Continue to: ASCCP guidelines...
ASCCP guidelines provide a framework to incorporate new data and technologies without major revision
Some noteworthy scenarios in ASCCP risk-based management are:
- For unsatisfactory cytology with a negative HPV test or no HPV test, repeat age-based screening in 2 to 4 months. (Note: A negative HPV test might reflect an inadequate specimen; do not interpret this result as a true negative.)
- An absent transformation zone (ie, between glandular and squamous cervical cells) with an otherwise adequate specimen should be interpreted as satisfactory for screening in patients 21 to 29 years of age. For those ≥ 30 years and with no HPV testing in this circumstance, HPV testing is preferred; repeating cytology, in 3 years, is also acceptable.
- After a finding of LSIL/CIN1 without evidence of a high-grade abnormality, and after 2 negative annual screenings (including HPV testing), a return to 3-year (not 5-year) screening is recommended.
- A cytology result of an HSIL carries a risk of 26% for CIN3+, in which case colposcopy is recommended, regardless of HPV test results.
- For long-term management after treatment for CIN2+, continue surveillance testing every 3 years after 3 consecutive negative HPV tests or cytology findings, for at least 25 years. If the 25-year threshold is reached before 65 years of age, continuing surveillance every 3 years is optional, as long as the patient is in good health (ie, life expectancy ≥ 10 years).
- After hysterectomy for a high-grade abnormality, annual vaginal HPV testing is recommended until 3 negative tests are returned; after that, surveillance shifts to a 3-year interval until the 25-year threshold.
Treatment of cancer precursors
Treatment for cervical dysplasia is excisional or ablative.
Excisional therapy. In most cases, excisional therapy (either a loop electrosurgical excision procedure [LEEP; also known as large loop excision of the transformation zone, cold knife conization, and laser conization] or cone biopsy) is required, or preferred. Excisional treatment has the advantage of providing a diagnostic specimen.
The World Health Organization recommends LEEP over ablation in settings in which LEEP is available.23 ASCCP states that, in the relatively few cases in which treatment is needed and it is for CIN1, either excision or ablation is acceptable. TABLE 416 lists situations in which excisional treatment is required because a diagnostic specimen is needed.
Continue to: Ablative treatments
Ablative treatments are cryotherapy, CO2 laser ablation, and thermal ablation. Ablative therapy has the advantage of presenting less risk of adverse obstetric outcomes (eg, preterm birth); it can be used if the indication for therapy is:
- CIN1 or CIN2 and HPV type 16 or 18 positivity
- concordant cytology and histology
- satisfactory colposcopy
- negative endocervical curettage.
The most common ablative treatment is liquid nitrogen applied to a metal tip under local anesthesia.
Hysterectomy can be considered for patients with recurrent CIN2+ who have completed childbearing or for whom repeat excision is infeasible (eg, scarring or a short cervix), or both.
Cost, availability, and convenience might play a role in decision-making with regard to the treatment choice for cancer precursors.
Is care after treatment called for? Patients who continue to be at increased risk of (and thus mortality from) cervical and vaginal cancer require enhanced surveillance. The risk of cancer is more than triple for patients who were given their diagnosis, and treated, when they were > 60 years, compared to patients treated in their 30s.1 The excess period of risk covers at least 25 years after treatment, even among patients who have had 3 posttreatment screenings.
Continue to: Persistent HPV positivity...
Persistent HPV positivity is more challenging. Patients infected with HPV type 16 have an increased risk of residual disease.
Cancer management
Invasive cancer. Most cervical cancers (60%) occur among patients who have not been screened during the 5 years before their diagnosis.24 For patients who have a diagnosis of cancer, those detected through screening have a much better prognosis than those identified by symptoms (mean cure rate, 92% and 66%, respectively).25 The median 5-year survival for patients who were not screened during the 5 years before their diagnosis of cervical cancer is 66%.2
In unscreened patients, cervical cancer usually manifests as abnormal vaginal bleeding, especially postcoitally. In approximately 45% of cases, the patient has localized disease at diagnosis; in 36%, regional disease; and in 15%, distant metastases.26
For cancers marked by stromal invasion < 3 mm, appropriate treatment is cone biopsy or simple hysterectomy.27
Most patients with early-stage cervical cancer undergo modified radical hysterectomy. The ovaries are usually conserved, unless the cancer is adenocarcinoma. Sentinel-node dissection has become standard practice. Primary radiation therapy is most often used for patients who are a poor surgical candidate because of medical comorbidity or poor functional status. Antiangiogenic agents (eg, bevacizumab) can be used as adjuvant palliative therapy for advanced and recurrent disease
Continue to: After treatment for...
After treatment for invasive cervical cancer, the goal is early detection of recurrence, although there is no consensus on a protocol. Most recurrences are detected within the first 2 years.
Long-term sequelae after treatment for advanced cancer are considerable. Patients report significantly lower quality of life,
Hormone replacement therapy is generally considered acceptable after treatment of cervical cancer because it does not increase replication of HPV.
Recurrent or metastatic cancer. Recurrence or metastases will develop in 15% to 60% of patients,30 usually within the first 2 years after treatment.
Management depends on location and extent of disease, using mainly radiation therapy or surgical resection. Recurrence or metastasis is usually incurable.
Continue to: Last, there are promising...
Last, there are promising areas of research for more effective treatment for cervical cancer precursors and cancers, including gene editing tools31 and therapeutic
Prospects for better cervical cancer care
Prevention. HPV vaccination is likely to have a large impact on population-based risk of both cancer and cancer precursors in the next generation.
Screening in the foreseeable future will gravitate toward reliance on primary HPV screening, with a self-sampling option.
Surveillance after dysplastic disease. The 2019 ASCCP guidelines for surveillance and intervention decisions after abnormal cancer screening results will evolve to incorporate introduction of new technology into computerized algorithms.
Treatment. New biologic therapies, including monoclonal antibodies and therapeutic vaccines against HPV, will likely be introduced for treating cancer precursors and invasive cancer.
A NOTE FROM THE EDITORS The Editors of The Journal of Family Practice recognize the importance of addressing the reproductive health of gender-diverse individuals. In this article, we use the words “women,” “men,” “girls,” and “boys” in limited circumstances (1) for ease of reading and (2) to reflect the official language of the US Food and Drug Administration and the Advisory Committee on Immunization Practices. The reader should consider the information and guidance offered in this discussion of cervical cancer and other human papillomavirus-related cancers to speak to the care of people with a uterine cervix and people with a penis.
CORRESPONDENCE
Linda Speer, MD, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; Linda.speer@utoledo.edu
The World Health Organization estimates that, in 2020, worldwide, there were 604,000 new cases of uterine cervical cancer and approximately 342,000 deaths, 84% of which occurred in developing countries.1 In the United States, as of 2018, the lifetime risk of death from cervical cancer was 2.2 for every 100,000
In this article, we summarize recent updates in the epidemiology, prevention, and treatment of cervical cancer. We emphasize recent information of value to family physicians, including updates in clinical guidelines and other pertinent national recommendations.
Spotlight continues to shine on HPV
It has been known for several decades that cervical cancer is caused by human papillomavirus (HPV). Of more than 100 known HPV types, 14 or 15 are classified as carcinogenic. HPV 16 is the most common oncogenic type, causing more than 60% of cases of cervical cancer3,4
HPV is the most common sexually transmitted infection, with as many as 80% of sexually active people becoming infected during their lifetime, generally before 50 years of age.5 HPV also causes other anogenital and oropharyngeal cancers; however, worldwide, more than 80% of HPV-associated cancers are cervical.6 Risk factors for cervical cancer are listed in TABLE 1.7 Cervical cancer is less common when partners are circumcised.7
Most cases of HPV infection clear in 1 or 2 years
At least 70% of cervical cancers are squamous cell carcinoma (SCC); 20% to 25% are adenocarcinoma (ADC); and < 3% to 5% are adenosquamous carcinoma.10 Almost 100% of cervical SCCs are HPV+, as are 86% of cervical ADCs. The most common reason for HPV-negative status in patients with cervical cancer is false-negative testing because of inadequate methods.
Primary prevention through vaccination
HPV vaccination was introduced in 2006 in the United States for girls,a and for boysa in 2011. The primary reason for vaccinating boys is to reduce the rates of HPV-related anal and oropharyngeal cancer. The only available HPV vaccine in the United States is Gardasil 9 (9-valent vaccine, recombinant; Merck), which provides coverage for 7 high-risk HPV types that account for approximately 90% of cervical cancers and 2 types (6 and 11) that are the principal causes of condylomata acuminata (genital warts). Future generations of prophylactic vaccines are expected to cover additional strains.
Continue to: Vaccine studies...
Vaccine studies have been summarized in a Cochrane review,11 showing that vaccination is highly effective for prevention of cervical dysplasia, especially when given to young girls and womena previously unexposed to the virus. It has not been fully established how long protection lasts, but vaccination appears to be 70% to 90% effective for ≥ 10 years.
Dosing schedule. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends a 2-dose schedule 6 to 15 months apart, for both girls and boys between 9 and 14 years of age.12 A third dose is indicated if the first and second doses were given less than 5 months apart, or the person is older than 15 years or is immunocompromised. No recommendation has been made for revaccination after the primary series.
In 2018, the US Food and Drug Administration approved Gardasil 9 for adults 27 to 45 years of age. In June 2019, ACIP recommended vaccination for mena as old as 26 years, and adopted a recommendation that unvaccinated men and women between 27 and 45 years discuss HPV vaccination with their physician.13
The adolescent HPV vaccination rate varies by state; however, all states lag behind the CDC’s Healthy People 2020 goal of 80%.14 Barriers to vaccination include cost, infrastructure limitations, and social stigma.
Secondary prevention: Screening and Tx of precancerous lesions
Cervical cancer screening identifies patients at increased risk of cervical cancer and reassures the great majority of them that their risk of cervical cancer is very low. There are 3 general approaches to cervical cancer screening:
- cytology-based screening, which has been implemented for decades in many countries
- primary testing for DNA or RNA markers of high-risk HPV types
- co-testing with cytology-based screening plus HPV testing.
Continue to: USPSTF guidance
USPSTF guidance. Recommendations of the US Preventive Services Task Force (USPSTF) for cervical cancer screening were updated in 2018 (TABLE 215). The recommendations state that high-risk HPV screening alone is a strategy that is amenable to patient self-sampling and self-mailing for processing—a protocol that has the potential to improve access
ASCCP guidance. The American Society of Colposcopy and Cervical Pathology (ASCCP) makes nearly the same recommendations for cervical cancer screening. An exception is that ASCCP guidelines allow for the possibility of screening using primary high-risk HPV testing for patients starting at 25 years of age.16
Screening programs that can be initiated at a later age and longer intervals should be possible once the adolescent vaccination rate is optimized and vaccination registries are widely implemented.
Cervical cytology protocol
Cervical cytologic abnormalities are reported using the Bethesda system. Specimen adequacy is the most important component of quality assurance,17 and is determined primarily by sufficient cellularity. However, any specimen containing abnormal squamous cells of undetermined significance (ASCUS) or atypical glandular cells (AGCs) is considered satisfactory, regardless of the number of cells. Obscuring factors that impair quality include excessive blood; inflammation; air-drying artifact; and an interfering substance, such as lubricant. The presence of reactive changes resulting from inflammation does not require further evaluation unless the patient is immunosuppressed.
Abnormalities are most often of squamous cells, of 2 categories: low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). HSILs are more likely to be associated with persistent HPV infection and higher risk of progression to cervical cancer.
Continue to: Cytologic findings...
Cytologic findings can be associated with histologic findings that are sometimes more, sometimes less, severe. LSIL cytology specimens that contain a few cells that are suspicious for HSIL, but that do not contain enough cells to be diagnostic, are reported as atypical squamous cells, and do not exclude a high-grade intraepithelial lesion.
Glandular-cell abnormalities usually originate from the glandular epithelium of the endocervix or the endometrium—most often, AGCs. Less frequent are AGCs, favor neoplasia; endocervical adenocarcinoma in situ; and ADC. Rarely, AGCs are associated with adenosquamous carcinoma. Endometrial polyps are a typical benign pathology that can be associated with AGCs.
In about 30% of cases, AGCs are associated with premalignant or malignant disease.18 The risk of malignancy in patients with AGCs increases with age, from < 2% among patients younger than 40 years to approximately 15% among those > 50 years.19 Endometrial malignancy is more common than cervical malignancy among patients > 40 years.
AGC cytology requires endocervical curettage, plus endometrial sampling for patients ≥ 35 years
Cytology-based screening has limitations. Sensitivity is relatively low and dependent on the expertise of the cytologist, although regular repeat testing has been used to overcome this limitation. A substantial subset of results are reported as equivocal—ie, ASCUS.
Continue to: Primary HPV screening
Primary HPV screening
Primary HPV testing was approved by the US Food and Drug Administration in 2015 and recommended as an appropriate screening option by professional societies
In contrast to cytology-based screening, HPV testing has high sensitivity (≥ 90%); the population-based negative likelihood ratio is near zero.20 This degree of sensitivity allows for extended screening intervals. However, primary HPV testing lacks specificity for persistent infection and high-grade or invasive lesions, which approximately doubles the number of patients who screen positive. The potential for excess patients to be referred for colposcopy led to the need for secondary triage.
Instituting secondary triage. Cytology is, currently, the primary method of secondary triage, reducing the number of referrals for colposcopy by nearly one-half, compared to referrals for all high-risk HPV results, and with better overall accuracy over cytology with high-risk HPV triage.21 When cytology shows ASCUS, or worse, refer the patient for colposcopy; alternatively, if so-called reflex testing for HPV types 16 and 18 is available and positive, direct referral to colposcopy without cytology is also appropriate.
In the future, secondary triage for cytology is likely to be replaced with improved technologies, such as immunostaining of the specimen for biomarkers associated with cervical precancer or cancer, or for viral genome methylation testing.22
Management of abnormal cervical cancer screening results
Routine screening applies to asymptomatic patients who do not require surveillance because they have not had prior abnormal screening results. In 2020, ASCCP published risk-based management consensus guidelines that were developed for abnormal cervical cancer screening tests and for cancer precursors.16 Guiding principles, and screening situations in which the guidelines can be applied, are summarized in TABLE 3
Continue to: ASCCP guidelines...
ASCCP guidelines provide a framework to incorporate new data and technologies without major revision
Some noteworthy scenarios in ASCCP risk-based management are:
- For unsatisfactory cytology with a negative HPV test or no HPV test, repeat age-based screening in 2 to 4 months. (Note: A negative HPV test might reflect an inadequate specimen; do not interpret this result as a true negative.)
- An absent transformation zone (ie, between glandular and squamous cervical cells) with an otherwise adequate specimen should be interpreted as satisfactory for screening in patients 21 to 29 years of age. For those ≥ 30 years and with no HPV testing in this circumstance, HPV testing is preferred; repeating cytology, in 3 years, is also acceptable.
- After a finding of LSIL/CIN1 without evidence of a high-grade abnormality, and after 2 negative annual screenings (including HPV testing), a return to 3-year (not 5-year) screening is recommended.
- A cytology result of an HSIL carries a risk of 26% for CIN3+, in which case colposcopy is recommended, regardless of HPV test results.
- For long-term management after treatment for CIN2+, continue surveillance testing every 3 years after 3 consecutive negative HPV tests or cytology findings, for at least 25 years. If the 25-year threshold is reached before 65 years of age, continuing surveillance every 3 years is optional, as long as the patient is in good health (ie, life expectancy ≥ 10 years).
- After hysterectomy for a high-grade abnormality, annual vaginal HPV testing is recommended until 3 negative tests are returned; after that, surveillance shifts to a 3-year interval until the 25-year threshold.
Treatment of cancer precursors
Treatment for cervical dysplasia is excisional or ablative.
Excisional therapy. In most cases, excisional therapy (either a loop electrosurgical excision procedure [LEEP; also known as large loop excision of the transformation zone, cold knife conization, and laser conization] or cone biopsy) is required, or preferred. Excisional treatment has the advantage of providing a diagnostic specimen.
The World Health Organization recommends LEEP over ablation in settings in which LEEP is available.23 ASCCP states that, in the relatively few cases in which treatment is needed and it is for CIN1, either excision or ablation is acceptable. TABLE 416 lists situations in which excisional treatment is required because a diagnostic specimen is needed.
Continue to: Ablative treatments
Ablative treatments are cryotherapy, CO2 laser ablation, and thermal ablation. Ablative therapy has the advantage of presenting less risk of adverse obstetric outcomes (eg, preterm birth); it can be used if the indication for therapy is:
- CIN1 or CIN2 and HPV type 16 or 18 positivity
- concordant cytology and histology
- satisfactory colposcopy
- negative endocervical curettage.
The most common ablative treatment is liquid nitrogen applied to a metal tip under local anesthesia.
Hysterectomy can be considered for patients with recurrent CIN2+ who have completed childbearing or for whom repeat excision is infeasible (eg, scarring or a short cervix), or both.
Cost, availability, and convenience might play a role in decision-making with regard to the treatment choice for cancer precursors.
Is care after treatment called for? Patients who continue to be at increased risk of (and thus mortality from) cervical and vaginal cancer require enhanced surveillance. The risk of cancer is more than triple for patients who were given their diagnosis, and treated, when they were > 60 years, compared to patients treated in their 30s.1 The excess period of risk covers at least 25 years after treatment, even among patients who have had 3 posttreatment screenings.
Continue to: Persistent HPV positivity...
Persistent HPV positivity is more challenging. Patients infected with HPV type 16 have an increased risk of residual disease.
Cancer management
Invasive cancer. Most cervical cancers (60%) occur among patients who have not been screened during the 5 years before their diagnosis.24 For patients who have a diagnosis of cancer, those detected through screening have a much better prognosis than those identified by symptoms (mean cure rate, 92% and 66%, respectively).25 The median 5-year survival for patients who were not screened during the 5 years before their diagnosis of cervical cancer is 66%.2
In unscreened patients, cervical cancer usually manifests as abnormal vaginal bleeding, especially postcoitally. In approximately 45% of cases, the patient has localized disease at diagnosis; in 36%, regional disease; and in 15%, distant metastases.26
For cancers marked by stromal invasion < 3 mm, appropriate treatment is cone biopsy or simple hysterectomy.27
Most patients with early-stage cervical cancer undergo modified radical hysterectomy. The ovaries are usually conserved, unless the cancer is adenocarcinoma. Sentinel-node dissection has become standard practice. Primary radiation therapy is most often used for patients who are a poor surgical candidate because of medical comorbidity or poor functional status. Antiangiogenic agents (eg, bevacizumab) can be used as adjuvant palliative therapy for advanced and recurrent disease
Continue to: After treatment for...
After treatment for invasive cervical cancer, the goal is early detection of recurrence, although there is no consensus on a protocol. Most recurrences are detected within the first 2 years.
Long-term sequelae after treatment for advanced cancer are considerable. Patients report significantly lower quality of life,
Hormone replacement therapy is generally considered acceptable after treatment of cervical cancer because it does not increase replication of HPV.
Recurrent or metastatic cancer. Recurrence or metastases will develop in 15% to 60% of patients,30 usually within the first 2 years after treatment.
Management depends on location and extent of disease, using mainly radiation therapy or surgical resection. Recurrence or metastasis is usually incurable.
Continue to: Last, there are promising...
Last, there are promising areas of research for more effective treatment for cervical cancer precursors and cancers, including gene editing tools31 and therapeutic
Prospects for better cervical cancer care
Prevention. HPV vaccination is likely to have a large impact on population-based risk of both cancer and cancer precursors in the next generation.
Screening in the foreseeable future will gravitate toward reliance on primary HPV screening, with a self-sampling option.
Surveillance after dysplastic disease. The 2019 ASCCP guidelines for surveillance and intervention decisions after abnormal cancer screening results will evolve to incorporate introduction of new technology into computerized algorithms.
Treatment. New biologic therapies, including monoclonal antibodies and therapeutic vaccines against HPV, will likely be introduced for treating cancer precursors and invasive cancer.
A NOTE FROM THE EDITORS The Editors of The Journal of Family Practice recognize the importance of addressing the reproductive health of gender-diverse individuals. In this article, we use the words “women,” “men,” “girls,” and “boys” in limited circumstances (1) for ease of reading and (2) to reflect the official language of the US Food and Drug Administration and the Advisory Committee on Immunization Practices. The reader should consider the information and guidance offered in this discussion of cervical cancer and other human papillomavirus-related cancers to speak to the care of people with a uterine cervix and people with a penis.
CORRESPONDENCE
Linda Speer, MD, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; Linda.speer@utoledo.edu
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. doi: 10.3322/caac.21660
2. Cancer stat facts: cervical cancer. National Cancer Institute Surveillance, Epidemiology, and End Results [SEER] Program. Accessed November 14, 2021. https://seer.cancer.gov/statfacts/html/cervix.html
3. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131:2349-2359. doi: 10.1002/ijc.27485
4. Winer RL, Hughes JP, Feng Q, et al. Early history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev. 2011;20:699-707. doi: 10.1158/1055-9965.EPI-10-1108
5. Chesson HW, Dunne EF, Hariri F, et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014;41:660-664. doi: 10.1097/OLQ.0000000000000193
6. Human papillomavirus (HPV) and cervical cancer. Fact sheet. Geneva, Switzerland: World Health Organization; November 11, 2020. Accessed November 14, 2021. www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer
7. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007;120:885-891. doi: 10.1002/ijc.22357
8. McCredie MRE, Sharples KJ, Paul C, et al. Natural history of cervical cancer neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008:9:425-434. doi: 10.1016/S1470-2045(08)70103-7
9. de Sanjose S, Quint WG, Alemany I, et al; . Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective, cross-sectional worldwide study. Lancet Oncol. 2010;11:1048-1056. doi: 10.1016/S1470-2045(10)70230-8
10. Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review 1975-2004. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2004/#citation
11. Arbyn M, Xu L, Simoens C, et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5:CD009069. doi: 10.1002/14651858.CD009069.pub3
12. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016:65;1405-1408. doi: 10.15585/mmwr.mm6549a5
13. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702. doi: 10.15585/mmwr.mm6832a3
14. State-level data: Female adolescents receiving 2 or 3 doses of HPV vaccine by age 13-15 years (percent). HealthyPeople.gov. Accessed November 14, 2021. www.healthypeople.gov/2020/data/map/4657?year=2018
15. United States Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;320:674-686. doi: 10.1001/jama.2018.10897
16. Perkins RB, Guido RS, Castle PE, et al; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2020;24:102-131. doi: 10.1097/LGT.0000000000000525
17. Nayar R, Wilbur DC. The Pap test and Bethesda 2014. Cancer Cytopathol. 2015;123;271-281. doi: 10.1002/cncy.21521
18. Schnatz PF, Guile M, O’Sullivan DM, et al. Clinical significance of atypical glandular cells on cervical cytology. Obstet Gynecol 2006;107:701-708. doi: 10.1097/01.AOG.0000202401.29145.68
19. Zhao C, Florea A, Onisko A, et al. Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: results from a large academic womens hospital laboratory employing sensitive screening methods. Gynecol Oncol 2009;114:383-389. doi: 10.1016/j.ygyno.2009.05.019
20. Zazove P, Reed BD, Gregoire L, et al. Low false-negative rate of PCR analysis for detecting human papillomavirus-related cervical lesions. J Clin Microbiol. 1998;36:2708-2713. doi: 10.1128/JCM.36.9.2708-2713.1998
21. Richardson LA, El-Zein M, Ramankumar AV, et al; . HPV DNA testing with cytology triage in cervical cancer screening: influence of revealing HPV infection status. Cancer Cytopathol. 2015:123:745-754. doi: 10.1002/cncy.21596
22. Wentzensen N, Schiffman M, Palmer T, et al. Triage of HPV positive women in cervical cancer screening. J Clin Virol 2016;76:S49-S55. doi: 10.1016/j.jcv.2015.11.015
23. WHO Guidelines: Use of Cryotherapy for Cervical Intraepithelial Neoplasia. Geneva, Switzerland: World Health Organization; 2011. Accessed November 14, 2021. www.ncbi.nlm.nih.gov/books/NBK138476/pdf/Bookshelf_NBK138476.pdf
24. Spence AR, Goggin P, Franco EL. Process of care failures in invasive cervical cancer: systematic review and meta-analysis. Prev Med. 2007:45:93-106. doi: 10.1016/j.ypmed.2007.06.007
25. Rositch AF, Nowak RG, Gravitt PE. Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000-2009. Cancer. 2014:120:2032-2038. doi: 10.1002/cncr.28548
26. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA: Cancer J Clin. 2021;71:7-33. doi: 10.3322/caac.21654
27. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: cervical cancer. Accessed June 15, 2021. www.nccn.org/professionals/physician_gls/pdf/cervical.pdf
28. Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390:1654-1663. doi: 10.1016/S0140-6736(17)31607-0
29. Osann K, Hsieh S, Nelson EL, et al. Factors associated with poor quality of life among cervical cancer survivors: implications for clinical care and clinical trials. Gynecol Oncol. 2014;135:266-272. doi: 10.1016/j.ygyno.2014.08.036
30. Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975 to 2003. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2003/#citation
31. Hu Z, Ding M. The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications. Cancer Med. 2018;7:5217-5236. doi: 10.1002/cam4.1501
32. Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: opportunity and challenge. Cancer Lett. 2020;471:88-102. doi: 10.1016/j.canlet.2019.11.039
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249. doi: 10.3322/caac.21660
2. Cancer stat facts: cervical cancer. National Cancer Institute Surveillance, Epidemiology, and End Results [SEER] Program. Accessed November 14, 2021. https://seer.cancer.gov/statfacts/html/cervix.html
3. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131:2349-2359. doi: 10.1002/ijc.27485
4. Winer RL, Hughes JP, Feng Q, et al. Early history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev. 2011;20:699-707. doi: 10.1158/1055-9965.EPI-10-1108
5. Chesson HW, Dunne EF, Hariri F, et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014;41:660-664. doi: 10.1097/OLQ.0000000000000193
6. Human papillomavirus (HPV) and cervical cancer. Fact sheet. Geneva, Switzerland: World Health Organization; November 11, 2020. Accessed November 14, 2021. www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer
7. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007;120:885-891. doi: 10.1002/ijc.22357
8. McCredie MRE, Sharples KJ, Paul C, et al. Natural history of cervical cancer neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008:9:425-434. doi: 10.1016/S1470-2045(08)70103-7
9. de Sanjose S, Quint WG, Alemany I, et al; . Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective, cross-sectional worldwide study. Lancet Oncol. 2010;11:1048-1056. doi: 10.1016/S1470-2045(10)70230-8
10. Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review 1975-2004. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2004/#citation
11. Arbyn M, Xu L, Simoens C, et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5:CD009069. doi: 10.1002/14651858.CD009069.pub3
12. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016:65;1405-1408. doi: 10.15585/mmwr.mm6549a5
13. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702. doi: 10.15585/mmwr.mm6832a3
14. State-level data: Female adolescents receiving 2 or 3 doses of HPV vaccine by age 13-15 years (percent). HealthyPeople.gov. Accessed November 14, 2021. www.healthypeople.gov/2020/data/map/4657?year=2018
15. United States Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;320:674-686. doi: 10.1001/jama.2018.10897
16. Perkins RB, Guido RS, Castle PE, et al; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2020;24:102-131. doi: 10.1097/LGT.0000000000000525
17. Nayar R, Wilbur DC. The Pap test and Bethesda 2014. Cancer Cytopathol. 2015;123;271-281. doi: 10.1002/cncy.21521
18. Schnatz PF, Guile M, O’Sullivan DM, et al. Clinical significance of atypical glandular cells on cervical cytology. Obstet Gynecol 2006;107:701-708. doi: 10.1097/01.AOG.0000202401.29145.68
19. Zhao C, Florea A, Onisko A, et al. Histologic follow-up results in 662 patients with Pap test findings of atypical glandular cells: results from a large academic womens hospital laboratory employing sensitive screening methods. Gynecol Oncol 2009;114:383-389. doi: 10.1016/j.ygyno.2009.05.019
20. Zazove P, Reed BD, Gregoire L, et al. Low false-negative rate of PCR analysis for detecting human papillomavirus-related cervical lesions. J Clin Microbiol. 1998;36:2708-2713. doi: 10.1128/JCM.36.9.2708-2713.1998
21. Richardson LA, El-Zein M, Ramankumar AV, et al; . HPV DNA testing with cytology triage in cervical cancer screening: influence of revealing HPV infection status. Cancer Cytopathol. 2015:123:745-754. doi: 10.1002/cncy.21596
22. Wentzensen N, Schiffman M, Palmer T, et al. Triage of HPV positive women in cervical cancer screening. J Clin Virol 2016;76:S49-S55. doi: 10.1016/j.jcv.2015.11.015
23. WHO Guidelines: Use of Cryotherapy for Cervical Intraepithelial Neoplasia. Geneva, Switzerland: World Health Organization; 2011. Accessed November 14, 2021. www.ncbi.nlm.nih.gov/books/NBK138476/pdf/Bookshelf_NBK138476.pdf
24. Spence AR, Goggin P, Franco EL. Process of care failures in invasive cervical cancer: systematic review and meta-analysis. Prev Med. 2007:45:93-106. doi: 10.1016/j.ypmed.2007.06.007
25. Rositch AF, Nowak RG, Gravitt PE. Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000-2009. Cancer. 2014:120:2032-2038. doi: 10.1002/cncr.28548
26. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA: Cancer J Clin. 2021;71:7-33. doi: 10.3322/caac.21654
27. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: cervical cancer. Accessed June 15, 2021. www.nccn.org/professionals/physician_gls/pdf/cervical.pdf
28. Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390:1654-1663. doi: 10.1016/S0140-6736(17)31607-0
29. Osann K, Hsieh S, Nelson EL, et al. Factors associated with poor quality of life among cervical cancer survivors: implications for clinical care and clinical trials. Gynecol Oncol. 2014;135:266-272. doi: 10.1016/j.ygyno.2014.08.036
30. Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975 to 2003. Bethesda, MD: National Cancer Institute; 2007. Accessed November 14, 2021. https://seer.cancer.gov/archive/csr/1975_2003/#citation
31. Hu Z, Ding M. The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications. Cancer Med. 2018;7:5217-5236. doi: 10.1002/cam4.1501
32. Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: opportunity and challenge. Cancer Lett. 2020;471:88-102. doi: 10.1016/j.canlet.2019.11.039
PRACTICE RECOMMENDATIONS
› Encourage eligible patients to be vaccinated against human papillomavirus (HPV) because the vaccine is highly effective for preventing cervical dysplasia, especially when given to patients previously unexposed to the virus. A
› Screen for cervical disease with either cytology plus HPV testing or primary HPV testing with secondary triage for cytology; both protocols are more accurate than screening with cervical cytology alone, and allow you to widen the screening interval. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
2021 CDC guidelines on sexually transmitted infections
In July 2021, the Centers for Disease Control and Prevention (CDC) published its updated guidelines on the diagnosis, treatment, and prevention of sexually transmitted infections (STIs).1 These guidelines were last published in 2015.2 Family physicians should be familiar with these guidelines as they are considered the standard of care for the treatment and prevention of STIs.
To revise the guidelines, the CDC convened a large panel that included CDC staff and subject matter experts from around the country. Using methodology borrowed from the US Preventive Services Task Force (USPSTF),3 the panel developed key questions and completed systematic reviews using a standard approach. The evidence behind key recommendations was ranked as high, medium, or low. However, the specific recommendations presented in the published guidelines appear without strength-of-recommendation descriptions or rankings of the levels of evidence supporting them.
The CDC approach to STI control involves 5 strategies (TABLE 1),1 which family physicians can implement as follows:
- Elicit an accurate sexual history.
- Discuss with patients and advise them on preventive interventions including barrier methods, microbicides, vaccines, and HIV pre-exposure prophylaxis.
- Order recommended screening tests for specific STIs from all sites of potential infection.
- Recognize the signs and symptoms of STIs and order recommended tests for confirmation.
- Treat confirmed infections using current recommended medications.
- Seek to advise, evaluate, and treat sex partners of those with documented STIs, and offer expedited partner therapy if allowed by state law.
- Perform recommended follow-up services for treated individuals.
Details on each of these strategies can be found in the new guidelines and are described for each specific pathogen and for specific demographic groups. Recommendations on screening for asymptomatic STIs can be found on the USPSTF website.4
The first step leading to targeted prevention strategies such as behavioral counseling, vaccination, and screening involves taking an accurate and complete sexual history. The CDC offers a 5-step process it calls the “5 Ps approach” to gathering needed information (TABLE 2).1
Major updates on the treatment of specific infections
Gonorrhea
The current recommendation for treating uncomplicated gonococcal infections of the cervix, urethra, pharynx, and rectum in adults and adolescents weighing < 150 kg is ceftriaxone 500 mg intramuscularly (IM) as a single dose; give 1 g for those weighing ≥ 150 kg.1 If co-infection with chlamydia has not been ruled out, co-treatment with doxycycline 100 mg po twice a day for 7 days is also recommended.1
This differs from the first-line treatment recommended in the previous guideline, which was dual therapy with ceftriaxone 250 mg IM and azithromycin 1 g po as a single dose, regardless of testing results for chlamydia.2 The higher dose for ceftriaxone now recommended is due to a gradual decrease in gonorrhea susceptibility to cephalosporins in recent years, although complete resistance remains rare. The move away from universal dual therapy reflects a concern about antibiotic stewardship and the potential effects of antibiotics on the microbiome. The elimination of azithromycin from recommended first-line therapies is due to a 10-fold increase in the proportion of bacterium isolates demonstrating reduced susceptibility, as measured by minimal inhibitory concentrations in the past few years.
Continue to: If ceftriaxone...
If ceftriaxone is unavailable, there are 2 alternative regimens: gentamicin 240 mg IM in a single dose, plus azithromycin 2 g po in a single dose; or cefixime 800 mg po in a single dose.1 However, these alternatives are not recommended for gonococcal infection of the pharynx, for which ceftriaxone should be used.
Counsel those treated for gonorrhea to avoid sexual activity for 7 days after treatment and until all sex partners have been treated. Because of the high rates of asymptomatic infections, tell patients to refer those with whom they have had sexual contact during the previous 60 days for evaluation, testing, and presumptive treatment.
Following treatment with the recommended dose of ceftriaxone, performing a test of cure is not recommended, with 1 exception: those with confirmed pharyngeal infection should be tested to confirm treatment success 7 to 14 days after being treated. However, all those treated for gonorrhea should be seen again in 3 months and retested to rule out reinfection, regardless of whether they think their sex partners have been adequately treated.
Chlamydia
The recommended first-line therapy for chlamydia is now doxycycline 100 mg twice a day for 7 days, which has proven to be superior to azithromycin (which was recommended as first-line therapy in 2015) for urogenital chlamydia in men and anal chlamydia in both men and women.1,2 Alternatives to doxycycline include azithromycin 1 g po as a single dose or levofloxacin 500 mg po once a day for 7 days.1 No test of cure is recommended; but as with gonorrhea, retesting at 3 months is recommended because of the risk for re-infection.
Instruct patients treated for chlamydia to avoid sexual intercourse for 7 days after therapy is initiated or until symptoms, if present, have resolved. To reduce the chances of reinfection, advise treated individuals to abstain from sexual intercourse until all of their sex partners have been treated.
Continue to: Sex partners...
Sex partners in the 60 days prior to the patient’s onset of symptoms or diagnosis should be advised to seek evaluation, testing, and presumptive treatment.
Trichomonas
The recommended first-line treatment for trichomonas now differs for men and women: metronidazole 2 g po as a single dose for men, and metronidazole 500 mg po twice a day for 7 days for women.1 Tinidazole 2 g po as a single dose is an alternative for both men and women. Previously, the single metronidazole dose was recommended for men and women,2 but there is now evidence that the 7-day course is markedly superior in achieving a cure in women.
No test of cure is recommended, but women should be retested at 3 months because of a high rate of re-infection. Current sex partners should be treated presumptively, and treated patients and their partners should avoid sex until all current sex partners have been treated. Consider expedited partner therapy if allowed by state law.
Bacterial vaginosis
First-line treatment recommendations for bacterial vaginosis (BV) have not changed: metronidazole 500 mg po twice a day for 7 days, or metronidazole gel 0.75% intravaginally daily for 5 days, or clindamycin cream 2% intravaginally at bedtime for 7 days. Advise women to avoid sexual activity or to use condoms for the duration of the treatment regimen.
A test of cure is not recommended if symptoms resolve, and no treatment or evaluation of sex partners is recommended. The guidelines describe several treatment options for women who have frequent, recurrent BV. To help prevent recurrences, they additionally suggest treating male partners with metronidazole 400 mg po twice a day and with 2% clindamycin cream applied to the penis twice a day, both for 7 days.
Continue to: Pelvic inflammatory disease
Pelvic inflammatory disease
Recommended regimens for treating pelvic inflammatory disease (PID) have changed (TABLES 3 and 4).1 Women with mild or moderate PID can be treated with intramuscular or oral regimens, as outcomes with these regimens are equivalent to those seen with intravenous treatments. The nonintravenous options all include 3 antibiotics: a cephalosporin, doxycycline, and metronidazole.
To minimize disease transmission, instruct women to avoid sex until therapy is complete, their symptoms have resolved, and sex partners have been treated. Sex partners of those with PID in the 60 days prior to the onset of symptoms should be evaluated, tested, and presumptively treated for chlamydia and gonorrhea.
Follow through on public health procedures
STIs are an important set of diseases from a public health perspective. Family physicians have the opportunity to assist with the prevention and control of these infections through screening, making accurate diagnoses, and applying recommended treatments. When you suspect that a patient has an STI, test for the most common ones: gonorrhea, chlamydia, HIV, and syphilis. Report all confirmed diagnoses to the local public health department and be prepared to refer patients’ sexual contacts to the local public health department or to provide contact evaluation and treatment.
Vaccines against STIs include hepatitis B vaccine, human papillomavirus vaccine, and hepatitis A vaccine. Offer these vaccines to all previously unvaccinated adolescents and young adults as per recommendations from the Advisory Committee on Immunization Practices.5
1. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:1-187.
2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.
3. USPSTF. Methods and processes. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes
4. USPSTF. Recommendations. Infectious diseases. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/topic_search_results?topic_status=P&category%5B%5D=18&searchterm=
5. CDC. Advisory Committee on Immunization Practices. COVID-19 ACIP vaccine recommendations. Accessed October 18, 2021. www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html
In July 2021, the Centers for Disease Control and Prevention (CDC) published its updated guidelines on the diagnosis, treatment, and prevention of sexually transmitted infections (STIs).1 These guidelines were last published in 2015.2 Family physicians should be familiar with these guidelines as they are considered the standard of care for the treatment and prevention of STIs.
To revise the guidelines, the CDC convened a large panel that included CDC staff and subject matter experts from around the country. Using methodology borrowed from the US Preventive Services Task Force (USPSTF),3 the panel developed key questions and completed systematic reviews using a standard approach. The evidence behind key recommendations was ranked as high, medium, or low. However, the specific recommendations presented in the published guidelines appear without strength-of-recommendation descriptions or rankings of the levels of evidence supporting them.
The CDC approach to STI control involves 5 strategies (TABLE 1),1 which family physicians can implement as follows:
- Elicit an accurate sexual history.
- Discuss with patients and advise them on preventive interventions including barrier methods, microbicides, vaccines, and HIV pre-exposure prophylaxis.
- Order recommended screening tests for specific STIs from all sites of potential infection.
- Recognize the signs and symptoms of STIs and order recommended tests for confirmation.
- Treat confirmed infections using current recommended medications.
- Seek to advise, evaluate, and treat sex partners of those with documented STIs, and offer expedited partner therapy if allowed by state law.
- Perform recommended follow-up services for treated individuals.
Details on each of these strategies can be found in the new guidelines and are described for each specific pathogen and for specific demographic groups. Recommendations on screening for asymptomatic STIs can be found on the USPSTF website.4
The first step leading to targeted prevention strategies such as behavioral counseling, vaccination, and screening involves taking an accurate and complete sexual history. The CDC offers a 5-step process it calls the “5 Ps approach” to gathering needed information (TABLE 2).1
Major updates on the treatment of specific infections
Gonorrhea
The current recommendation for treating uncomplicated gonococcal infections of the cervix, urethra, pharynx, and rectum in adults and adolescents weighing < 150 kg is ceftriaxone 500 mg intramuscularly (IM) as a single dose; give 1 g for those weighing ≥ 150 kg.1 If co-infection with chlamydia has not been ruled out, co-treatment with doxycycline 100 mg po twice a day for 7 days is also recommended.1
This differs from the first-line treatment recommended in the previous guideline, which was dual therapy with ceftriaxone 250 mg IM and azithromycin 1 g po as a single dose, regardless of testing results for chlamydia.2 The higher dose for ceftriaxone now recommended is due to a gradual decrease in gonorrhea susceptibility to cephalosporins in recent years, although complete resistance remains rare. The move away from universal dual therapy reflects a concern about antibiotic stewardship and the potential effects of antibiotics on the microbiome. The elimination of azithromycin from recommended first-line therapies is due to a 10-fold increase in the proportion of bacterium isolates demonstrating reduced susceptibility, as measured by minimal inhibitory concentrations in the past few years.
Continue to: If ceftriaxone...
If ceftriaxone is unavailable, there are 2 alternative regimens: gentamicin 240 mg IM in a single dose, plus azithromycin 2 g po in a single dose; or cefixime 800 mg po in a single dose.1 However, these alternatives are not recommended for gonococcal infection of the pharynx, for which ceftriaxone should be used.
Counsel those treated for gonorrhea to avoid sexual activity for 7 days after treatment and until all sex partners have been treated. Because of the high rates of asymptomatic infections, tell patients to refer those with whom they have had sexual contact during the previous 60 days for evaluation, testing, and presumptive treatment.
Following treatment with the recommended dose of ceftriaxone, performing a test of cure is not recommended, with 1 exception: those with confirmed pharyngeal infection should be tested to confirm treatment success 7 to 14 days after being treated. However, all those treated for gonorrhea should be seen again in 3 months and retested to rule out reinfection, regardless of whether they think their sex partners have been adequately treated.
Chlamydia
The recommended first-line therapy for chlamydia is now doxycycline 100 mg twice a day for 7 days, which has proven to be superior to azithromycin (which was recommended as first-line therapy in 2015) for urogenital chlamydia in men and anal chlamydia in both men and women.1,2 Alternatives to doxycycline include azithromycin 1 g po as a single dose or levofloxacin 500 mg po once a day for 7 days.1 No test of cure is recommended; but as with gonorrhea, retesting at 3 months is recommended because of the risk for re-infection.
Instruct patients treated for chlamydia to avoid sexual intercourse for 7 days after therapy is initiated or until symptoms, if present, have resolved. To reduce the chances of reinfection, advise treated individuals to abstain from sexual intercourse until all of their sex partners have been treated.
Continue to: Sex partners...
Sex partners in the 60 days prior to the patient’s onset of symptoms or diagnosis should be advised to seek evaluation, testing, and presumptive treatment.
Trichomonas
The recommended first-line treatment for trichomonas now differs for men and women: metronidazole 2 g po as a single dose for men, and metronidazole 500 mg po twice a day for 7 days for women.1 Tinidazole 2 g po as a single dose is an alternative for both men and women. Previously, the single metronidazole dose was recommended for men and women,2 but there is now evidence that the 7-day course is markedly superior in achieving a cure in women.
No test of cure is recommended, but women should be retested at 3 months because of a high rate of re-infection. Current sex partners should be treated presumptively, and treated patients and their partners should avoid sex until all current sex partners have been treated. Consider expedited partner therapy if allowed by state law.
Bacterial vaginosis
First-line treatment recommendations for bacterial vaginosis (BV) have not changed: metronidazole 500 mg po twice a day for 7 days, or metronidazole gel 0.75% intravaginally daily for 5 days, or clindamycin cream 2% intravaginally at bedtime for 7 days. Advise women to avoid sexual activity or to use condoms for the duration of the treatment regimen.
A test of cure is not recommended if symptoms resolve, and no treatment or evaluation of sex partners is recommended. The guidelines describe several treatment options for women who have frequent, recurrent BV. To help prevent recurrences, they additionally suggest treating male partners with metronidazole 400 mg po twice a day and with 2% clindamycin cream applied to the penis twice a day, both for 7 days.
Continue to: Pelvic inflammatory disease
Pelvic inflammatory disease
Recommended regimens for treating pelvic inflammatory disease (PID) have changed (TABLES 3 and 4).1 Women with mild or moderate PID can be treated with intramuscular or oral regimens, as outcomes with these regimens are equivalent to those seen with intravenous treatments. The nonintravenous options all include 3 antibiotics: a cephalosporin, doxycycline, and metronidazole.
To minimize disease transmission, instruct women to avoid sex until therapy is complete, their symptoms have resolved, and sex partners have been treated. Sex partners of those with PID in the 60 days prior to the onset of symptoms should be evaluated, tested, and presumptively treated for chlamydia and gonorrhea.
Follow through on public health procedures
STIs are an important set of diseases from a public health perspective. Family physicians have the opportunity to assist with the prevention and control of these infections through screening, making accurate diagnoses, and applying recommended treatments. When you suspect that a patient has an STI, test for the most common ones: gonorrhea, chlamydia, HIV, and syphilis. Report all confirmed diagnoses to the local public health department and be prepared to refer patients’ sexual contacts to the local public health department or to provide contact evaluation and treatment.
Vaccines against STIs include hepatitis B vaccine, human papillomavirus vaccine, and hepatitis A vaccine. Offer these vaccines to all previously unvaccinated adolescents and young adults as per recommendations from the Advisory Committee on Immunization Practices.5
In July 2021, the Centers for Disease Control and Prevention (CDC) published its updated guidelines on the diagnosis, treatment, and prevention of sexually transmitted infections (STIs).1 These guidelines were last published in 2015.2 Family physicians should be familiar with these guidelines as they are considered the standard of care for the treatment and prevention of STIs.
To revise the guidelines, the CDC convened a large panel that included CDC staff and subject matter experts from around the country. Using methodology borrowed from the US Preventive Services Task Force (USPSTF),3 the panel developed key questions and completed systematic reviews using a standard approach. The evidence behind key recommendations was ranked as high, medium, or low. However, the specific recommendations presented in the published guidelines appear without strength-of-recommendation descriptions or rankings of the levels of evidence supporting them.
The CDC approach to STI control involves 5 strategies (TABLE 1),1 which family physicians can implement as follows:
- Elicit an accurate sexual history.
- Discuss with patients and advise them on preventive interventions including barrier methods, microbicides, vaccines, and HIV pre-exposure prophylaxis.
- Order recommended screening tests for specific STIs from all sites of potential infection.
- Recognize the signs and symptoms of STIs and order recommended tests for confirmation.
- Treat confirmed infections using current recommended medications.
- Seek to advise, evaluate, and treat sex partners of those with documented STIs, and offer expedited partner therapy if allowed by state law.
- Perform recommended follow-up services for treated individuals.
Details on each of these strategies can be found in the new guidelines and are described for each specific pathogen and for specific demographic groups. Recommendations on screening for asymptomatic STIs can be found on the USPSTF website.4
The first step leading to targeted prevention strategies such as behavioral counseling, vaccination, and screening involves taking an accurate and complete sexual history. The CDC offers a 5-step process it calls the “5 Ps approach” to gathering needed information (TABLE 2).1
Major updates on the treatment of specific infections
Gonorrhea
The current recommendation for treating uncomplicated gonococcal infections of the cervix, urethra, pharynx, and rectum in adults and adolescents weighing < 150 kg is ceftriaxone 500 mg intramuscularly (IM) as a single dose; give 1 g for those weighing ≥ 150 kg.1 If co-infection with chlamydia has not been ruled out, co-treatment with doxycycline 100 mg po twice a day for 7 days is also recommended.1
This differs from the first-line treatment recommended in the previous guideline, which was dual therapy with ceftriaxone 250 mg IM and azithromycin 1 g po as a single dose, regardless of testing results for chlamydia.2 The higher dose for ceftriaxone now recommended is due to a gradual decrease in gonorrhea susceptibility to cephalosporins in recent years, although complete resistance remains rare. The move away from universal dual therapy reflects a concern about antibiotic stewardship and the potential effects of antibiotics on the microbiome. The elimination of azithromycin from recommended first-line therapies is due to a 10-fold increase in the proportion of bacterium isolates demonstrating reduced susceptibility, as measured by minimal inhibitory concentrations in the past few years.
Continue to: If ceftriaxone...
If ceftriaxone is unavailable, there are 2 alternative regimens: gentamicin 240 mg IM in a single dose, plus azithromycin 2 g po in a single dose; or cefixime 800 mg po in a single dose.1 However, these alternatives are not recommended for gonococcal infection of the pharynx, for which ceftriaxone should be used.
Counsel those treated for gonorrhea to avoid sexual activity for 7 days after treatment and until all sex partners have been treated. Because of the high rates of asymptomatic infections, tell patients to refer those with whom they have had sexual contact during the previous 60 days for evaluation, testing, and presumptive treatment.
Following treatment with the recommended dose of ceftriaxone, performing a test of cure is not recommended, with 1 exception: those with confirmed pharyngeal infection should be tested to confirm treatment success 7 to 14 days after being treated. However, all those treated for gonorrhea should be seen again in 3 months and retested to rule out reinfection, regardless of whether they think their sex partners have been adequately treated.
Chlamydia
The recommended first-line therapy for chlamydia is now doxycycline 100 mg twice a day for 7 days, which has proven to be superior to azithromycin (which was recommended as first-line therapy in 2015) for urogenital chlamydia in men and anal chlamydia in both men and women.1,2 Alternatives to doxycycline include azithromycin 1 g po as a single dose or levofloxacin 500 mg po once a day for 7 days.1 No test of cure is recommended; but as with gonorrhea, retesting at 3 months is recommended because of the risk for re-infection.
Instruct patients treated for chlamydia to avoid sexual intercourse for 7 days after therapy is initiated or until symptoms, if present, have resolved. To reduce the chances of reinfection, advise treated individuals to abstain from sexual intercourse until all of their sex partners have been treated.
Continue to: Sex partners...
Sex partners in the 60 days prior to the patient’s onset of symptoms or diagnosis should be advised to seek evaluation, testing, and presumptive treatment.
Trichomonas
The recommended first-line treatment for trichomonas now differs for men and women: metronidazole 2 g po as a single dose for men, and metronidazole 500 mg po twice a day for 7 days for women.1 Tinidazole 2 g po as a single dose is an alternative for both men and women. Previously, the single metronidazole dose was recommended for men and women,2 but there is now evidence that the 7-day course is markedly superior in achieving a cure in women.
No test of cure is recommended, but women should be retested at 3 months because of a high rate of re-infection. Current sex partners should be treated presumptively, and treated patients and their partners should avoid sex until all current sex partners have been treated. Consider expedited partner therapy if allowed by state law.
Bacterial vaginosis
First-line treatment recommendations for bacterial vaginosis (BV) have not changed: metronidazole 500 mg po twice a day for 7 days, or metronidazole gel 0.75% intravaginally daily for 5 days, or clindamycin cream 2% intravaginally at bedtime for 7 days. Advise women to avoid sexual activity or to use condoms for the duration of the treatment regimen.
A test of cure is not recommended if symptoms resolve, and no treatment or evaluation of sex partners is recommended. The guidelines describe several treatment options for women who have frequent, recurrent BV. To help prevent recurrences, they additionally suggest treating male partners with metronidazole 400 mg po twice a day and with 2% clindamycin cream applied to the penis twice a day, both for 7 days.
Continue to: Pelvic inflammatory disease
Pelvic inflammatory disease
Recommended regimens for treating pelvic inflammatory disease (PID) have changed (TABLES 3 and 4).1 Women with mild or moderate PID can be treated with intramuscular or oral regimens, as outcomes with these regimens are equivalent to those seen with intravenous treatments. The nonintravenous options all include 3 antibiotics: a cephalosporin, doxycycline, and metronidazole.
To minimize disease transmission, instruct women to avoid sex until therapy is complete, their symptoms have resolved, and sex partners have been treated. Sex partners of those with PID in the 60 days prior to the onset of symptoms should be evaluated, tested, and presumptively treated for chlamydia and gonorrhea.
Follow through on public health procedures
STIs are an important set of diseases from a public health perspective. Family physicians have the opportunity to assist with the prevention and control of these infections through screening, making accurate diagnoses, and applying recommended treatments. When you suspect that a patient has an STI, test for the most common ones: gonorrhea, chlamydia, HIV, and syphilis. Report all confirmed diagnoses to the local public health department and be prepared to refer patients’ sexual contacts to the local public health department or to provide contact evaluation and treatment.
Vaccines against STIs include hepatitis B vaccine, human papillomavirus vaccine, and hepatitis A vaccine. Offer these vaccines to all previously unvaccinated adolescents and young adults as per recommendations from the Advisory Committee on Immunization Practices.5
1. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:1-187.
2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.
3. USPSTF. Methods and processes. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes
4. USPSTF. Recommendations. Infectious diseases. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/topic_search_results?topic_status=P&category%5B%5D=18&searchterm=
5. CDC. Advisory Committee on Immunization Practices. COVID-19 ACIP vaccine recommendations. Accessed October 18, 2021. www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html
1. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:1-187.
2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.
3. USPSTF. Methods and processes. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes
4. USPSTF. Recommendations. Infectious diseases. Accessed November 17, 2021. https://uspreventiveservicestaskforce.org/uspstf/topic_search_results?topic_status=P&category%5B%5D=18&searchterm=
5. CDC. Advisory Committee on Immunization Practices. COVID-19 ACIP vaccine recommendations. Accessed October 18, 2021. www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html
