OBG Management

Although precise data are unavailable, it was estimated in 2011 that there were nearly 700,000 transgendered persons in the United States.¹ This means that gynecologists in certain locales regularly encounter transgender patients in clinical practice.

At the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG), held May 2-6 in San Francisco, California, Dr. Cecile A. Unger discussed the role of the gynecologist in the care of transgender patients.

In this interview with OBG Management, Dr. Unger discusses:

• pertinent terminology, including gender dysphoria, and important clinical aspects of examining and treating a transgender patient
• what a clinician be screening for in general, as well as specifically, in the transgender population, including considerations for when a patient is undergoing hormone therapy
• the importance of developing trust and how that can be accomplished.

Although precise data are unavailable, it was estimated in 2011 that there were nearly 700,000 transgendered persons in the United States.¹ This means that gynecologists in certain locales regularly encounter transgender patients in clinical practice.

At the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG), held May 2-6 in San Francisco, California, Dr. Cecile A. Unger discussed the role of the gynecologist in the care of transgender patients.

In this interview with OBG Management, Dr. Unger discusses:

• pertinent terminology, including gender dysphoria, and important clinical aspects of examining and treating a transgender patient
• what a clinician be screening for in general, as well as specifically, in the transgender population, including considerations for when a patient is undergoing hormone therapy
• the importance of developing trust and how that can be accomplished.

Although precise data are unavailable, it was estimated in 2011 that there were nearly 700,000 transgendered persons in the United States.¹ This means that gynecologists in certain locales regularly encounter transgender patients in clinical practice.

At the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG), held May 2-6 in San Francisco, California, Dr. Cecile A. Unger discussed the role of the gynecologist in the care of transgender patients.

In this interview with OBG Management, Dr. Unger discusses:

• pertinent terminology, including gender dysphoria, and important clinical aspects of examining and treating a transgender patient
• what a clinician be screening for in general, as well as specifically, in the transgender population, including considerations for when a patient is undergoing hormone therapy
• the importance of developing trust and how that can be accomplished.

The relative safety of instrumental rotations in the second stage of labor remains controversial. Older reports suggest an unacceptable risk of fetal injury, while recent studies demonstrate more favorable outcomes without significant fetal or maternal morbidity. This study by Aiken and colleagues goes one step further by using propensity analysis to adjust for the likelihood of receiving an attempted instrumental rotation.

Details of the study
With a cohort of 833 women with second-stage positional abnormalities, Aiken and colleagues compared maternal and newborn outcomes associated with cesarean delivery (n = 534) with those of an attempted rotational procedure (n = 334). Among the attempted instrumental rotations, 299 (90%) were successful. By intention to treat, failed attempts at rotation and vaginal delivery were included in the instrumental rotation group. The authors relied on propensity analy­sis to adjust for selection bias.

Strengths and weaknesses
The main strengths of this study are the relatively large sample size, the inclusion of failed procedures in the forceps group based on intention to treat, the robust approach to adjusting for the likelihood of undergoing an attempted rotation, and the contemporary nature of the cohort.

However, the study has 4 important limitations:

What this evidence means for practice
Although this study does have limitations, it adds to the increasing number of contemporary reports suggesting that instrumental rotational procedures are safe. Though it is not without challenges, training in rotational forceps should continue.
— William H. Barth Jr, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The relative safety of instrumental rotations in the second stage of labor remains controversial. Older reports suggest an unacceptable risk of fetal injury, while recent studies demonstrate more favorable outcomes without significant fetal or maternal morbidity. This study by Aiken and colleagues goes one step further by using propensity analysis to adjust for the likelihood of receiving an attempted instrumental rotation.

Details of the study
With a cohort of 833 women with second-stage positional abnormalities, Aiken and colleagues compared maternal and newborn outcomes associated with cesarean delivery (n = 534) with those of an attempted rotational procedure (n = 334). Among the attempted instrumental rotations, 299 (90%) were successful. By intention to treat, failed attempts at rotation and vaginal delivery were included in the instrumental rotation group. The authors relied on propensity analy­sis to adjust for selection bias.

Strengths and weaknesses
The main strengths of this study are the relatively large sample size, the inclusion of failed procedures in the forceps group based on intention to treat, the robust approach to adjusting for the likelihood of undergoing an attempted rotation, and the contemporary nature of the cohort.

However, the study has 4 important limitations:

What this evidence means for practice
Although this study does have limitations, it adds to the increasing number of contemporary reports suggesting that instrumental rotational procedures are safe. Though it is not without challenges, training in rotational forceps should continue.
— William H. Barth Jr, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The relative safety of instrumental rotations in the second stage of labor remains controversial. Older reports suggest an unacceptable risk of fetal injury, while recent studies demonstrate more favorable outcomes without significant fetal or maternal morbidity. This study by Aiken and colleagues goes one step further by using propensity analysis to adjust for the likelihood of receiving an attempted instrumental rotation.

Details of the study
With a cohort of 833 women with second-stage positional abnormalities, Aiken and colleagues compared maternal and newborn outcomes associated with cesarean delivery (n = 534) with those of an attempted rotational procedure (n = 334). Among the attempted instrumental rotations, 299 (90%) were successful. By intention to treat, failed attempts at rotation and vaginal delivery were included in the instrumental rotation group. The authors relied on propensity analy­sis to adjust for selection bias.

Strengths and weaknesses
The main strengths of this study are the relatively large sample size, the inclusion of failed procedures in the forceps group based on intention to treat, the robust approach to adjusting for the likelihood of undergoing an attempted rotation, and the contemporary nature of the cohort.

However, the study has 4 important limitations:

What this evidence means for practice
Although this study does have limitations, it adds to the increasing number of contemporary reports suggesting that instrumental rotational procedures are safe. Though it is not without challenges, training in rotational forceps should continue.
— William H. Barth Jr, MD

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Two very recent significant advances in cervical disease prevention and screening make this an exciting time for women’s health clinicians. One development, the 9-valent human papillomavirus (HPV) vaccine, offers the potential to increase overall prevention of cervical cancer to over 90%. The other advance offers clinicians a cervical cancer screening alternative, HPV DNA testing, for primary cervical cancer screening. In this article, I underscore the data behind, as well as expert guidance on, these two important developments.
 

The 9-valent HPV vaccine expands HPV-type coverage and vaccine options for routine use
Joura EA, Giuliano AR, Iversen O, et al. A 9-valent vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–723.

Two HPV types, 16 and 18, cause the majority—about 70%—of cervical cancers. Vaccination against these types, as well as against types 6 and 11 that cause most condyloma, has been available in the United States since 2006, when the quadrivalent vaccine was approved by the US Food and Drug Administration (FDA).¹ Now, based on the results of Joura and colleagues’ randomized, double-blind phase 2b−3 study involving more than 14,000 women, the 9-valent vaccine (Gardasil 9, Merck, Whitehouse Station, New Jersey) has been recommended by the Advisory Committee on Immunization Practices (ACIP) as 1 of 3 HPV vaccines that can be used for routine vaccination.¹ (The other 2 vaccines include the bivalent [Cervarix, GlaxoSmithKline, Research Triangle Park, North Carolina] and quadrivalent [Gardasil, Merck]).

Compared with quadrivalent, does the 9-valent vaccine offer compelling additional protection?
The incidence rate of high-grade cervical intraepithelial neoplasia (CIN; ≥CIN 2 or adenocarcinoma in situ) related to the ­additional HPV types covered with the 9-valent vaccine (31, 33, 45, 52, and 58) was 0.1 per 1,000 ­person-years in the 9-valent group and 1.6 per 1,000 person-years in the quadrivalent group. This is equivalent to 1 case versus 30 cases of disease and translates to 96.7% efficacy (95% confidence interval [CI], 80.9−99.8) against these 5 additional high-risk HPV types. At 36 months, there was 1 case of high-grade cervical disease in the 9-valent group related to the 5 additional HPV types, compared with 20 cumulative cases in the quadrivalent group. At 48 months, there was 1 case in the 9-valent group and 27 cases in the quadrivalent group (FIGURE 1).

This expanded disease coverage means the vaccine has the potential to prevent an additional 15% to 20% of cervical cancers in addition to the potential to prevent 5% to 20% of other HPV-related cancers.³

The added HPV-type protection resulted in more frequent injection site reactions (90.7% in the 9-valent group vs 84.9% in the quadrivalent group). Pain, erythema, and pruritis were the most common reactions. While rare, events of severe intensity were more common in the 9-valent group. However, less than 0.1% of participants discontinued study vaccination because of a vaccine-related adverse event.

Study strengths and weaknesses
This was a well-designed prospective, randomized controlled trial. Follow-up was ­limited; however, this is typical for a clinical trial, and extended follow-up analyses have held up in other HPV vaccine trials; I don’t anticipate it will be any different in this case. The control arm in the case of this trial was the quadrivalent vaccine, as that is the routinely recommended vaccine, so it is not ethical to give placebo in this age-range population. The placebo study already was published,⁴ so Joura and colleagues’ results build on prior findings. 

What this EVIDENCE means for practice
In a widely vaccinated population, the 9-valent HPV vaccine has the potential to protect against an additional 20% of cervical cancers, compared with the quadrivalent vaccine. This is an important improvement in HPV infection and cervical disease prevention. Unfortunately, in the United States we still have very low coverage for the first dose of the HPV vaccine, and even lower coverage for the recommended 3-dose series. This is a big problem in the United States. Stakeholders and advocates need to figure out innovative ways to overcome the challenges of full vaccination for the patients in whom it’s routinely recommended—11- and 12-year-old girls and boys. HPV vaccination lags behind coverage for other vaccines recommended in this same age group—by 20% to 25%.³ US HPV vaccination rates are woefully low in comparison with such other countries as Australia, much of western Europe, and the UK. “If teenagers were offered and accepted HPV vaccination every time they received another vaccine, first-dose coverage for HPV would exceed 90%.”³

The ACIP recommends routine vaccination for HPV—with the bivalent, quadrivalent, or 9-valent vaccine—at age 11 or 12 years. They also recommend vaccination for females aged 13 through 26 years and males aged 13 through 21 years who have not been vaccinated previously. Vaccination is also recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously.¹

By the time I retire, I hope that the impact of protection against additional HPV infection types will be felt, with HPV vaccination rates improved and fewer women affected by the morbidity and mortality related to cervical cancer. As ObGyns, we want to do right by our patients; we need to embrace and continue to discuss the message of primary protection with vaccines that protect against HPV in order to overcome the mixed rhetoric patients and parents receive from other groups, including sensational media or political figureheads who might have an alternative agenda that is clearly not in the best interest of our patients.

HPV test alone is as effective as Pap plus HPV test for cervical disease screening
Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189–197.

The cobas (Roche Molecular Diagnostics, Pleasanton, California) HPV DNA test received FDA approval as a primary screening test for cervical cancer in women aged 25 and older in April 2015. This is a big paradigm shift from what has long been the way we screen women, starting with cytology. Simplistically, the thinking is that we start with the more sensitive test to enrich the population of women that might need additional testing, which might include cytology.

The FDA considered these end-of-study data by Wright and colleagues, which had not been publically published at the time, in its decision. With the Addressing the Need for Advanced HPV Diagnostics (ATHENA) 3-year prospective study, these investigators sought to address major unresolved issues related to HPV primary screening, such as determining which HPV-positive women should be referred to colposcopy and how HPV primary screening performs in the United States. Such a strategy long has been shown to be effective in large prospective European trials.

Details of the study
Three screening strategies were tested:

In all strategies, women who were referred to colposcopy and found not to have CIN 2 or greater were rescreened with both tests in 1 year and referred to colposcopy if the finding was ASC-US or higher-grade or persistently HPV-positive.

Of the 3 screening strategies, HPV primary in women 25 years and older had the highest adjusted sensitivity over 3 years (76.1%; 95% CI, 70.3–81.8) for the detection of CIN 3 or greater, with similar specificity as the cytology and hybrid strategies. In addition, the negative predictive value for not having clinically relevant disease for HPV primary was comparable to or better than the other 2 strategies (TABLE).⁵

Another important finding was that the number of colposcopies required to detect 1 case of cervical disease, although found to be significantly higher, was comparable for the HPV primary and cytology strategies (7.1 [95% CI, 6.4–8.0] for cytology vs 8.0 for HPV primary for CIN 2 or greater in women 25 years and older). For CIN 3 or greater, the number of colposcopies required to detect 1 case was 12.8 (95% CI, 11.7–14.5) for HPV primary versus 12.9 (95% CI, 11.5–14.8) for hybrid and 10.8 (95% CI, 9.4–12.6) for cytology.

What this EVIDENCE means for practice
These data indicate that HPV primary screening in women aged 25 and older is as effective as a hybrid screening strategy that uses cytology and cotesting in a patient older than 30 years. And HPV primary screening requires fewer overall screening tests to identify women who have clinically significant cervical disease.

Importantly, compared with a cytology-based strategy, the negative predictive value is quite high for HPV primary screening. Therefore, if someone has a negative HPV test result, the likelihood of that person actually having some sort of clinically relevant disease that day or in the next 3 years is incredibly low. And this is really what’s important for our patients who are getting screened for cervical cancer.

Interim guidelines support use of HPV testing alone or with the Pap smear
Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol. 2015;136(2):178–182.

The most recent set of consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors is the American Cancer ­Society/­American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology 2012 guidelines,⁶ which recommend cotesting as the preferred strategy in women aged 30 to 65 years. However, to address increasing evidence that HPV testing alone is an effective primary screening approach and how clinicians should adopt these findings in their practice, an expert panel convened to offer interim guidance. The panel was cosponsored and funded by the Society of Gynecologic Oncology (SGO) and ASCCP and included 13 experts representing 7 societies, including SGO, ASCCP, and the American College of Obstetricians and Gynecologists. This guidance can be adopted as an alternative to the updated 2012 ­recommendations until the next consensus guidelines panel convenes.

The panel considered a number of questions related to primary HPV testing and overall advantages and disadvantages of this strategy for screening.

Is HPV testing (for high-risk HPV [hrHPV] types) for primary screening as safe and effective as cytology-based screening?
The panel’s answer: Yes. A negative hrHPV test provides greater reassurance of low CIN 3 or greater risk than a negative cytology result. Because of its equivalent, or even superior, effectiveness—which has been demonstrated in the ATHENA study and several European randomized controlled screening trials^7,8—primary hrHPV screening can be considered as an alternative to current US cervical cancer screening methods.

A reasonable approach to managing a positive hrHPV result, advises the panel, is to triage hrHPV-positive women using a combination of genotyping for HPV 16 and 18 and reflex cytology for women positive for the 12 other hrHPV genotypes
(FIGURE 2).⁹

What is the optimal age to begin primary hrHPV screening?
The panel’s clinical guidance is not before age 25. This is a gray area right now, however, as there are concerns regarding the potential harm of screening at age 25 despite the increased detection of disease, particularly with regard to the number of colposcopies that could be performed in this age group due to the high incidence of HPV infection in young women. So the ideal age at which to begin hrHPV screening will need further discussion in future consensus guideline panels.

What is the optimal interval for primary hrHPV screening?
Prospective follow-up in the ATHENA study was restricted to 3 years. The panel advises that rescreening after a negative primary hrHPV screen should occur no sooner than every 3 years.

Outstanding considerations
The changeover from primary cytology to primary HPV testing represents a very different workflow for clinicians and laboratories. It also represents a different mode of screening for our patients, so patient education is essential. Many questions and concerns still need to be considered, for instance:

What this EVIDENCE means for practice
A move to the HPV test for primary screening represents a paradigm shift for clinicians and patients. Such a shift likely will be slow to occur, due to changes in clinical and laboratory workflow, provider and patient education, and systems issues. Also, there are a number of questions that still need to be answered. Primary hrHPV screening at age 25 to 29 years may lead to increased CIN 3 detection, but the impact of the increased number of colposcopies, integration for those women who already have been screened prior to age 25, and actual impact on cancer prevention need further investigation, the panel points out.

However, primary HPV screening can be considered as an alternative to current US cytology-based cervical cancer screening approaches. Over time, use of primary HPV screening appears to make screening more precise and efficient as it will minimize the number of abnormal cytology results that we would consider cytomorphologic manifestations of an active HPV infection that are not clinically relevant.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Two very recent significant advances in cervical disease prevention and screening make this an exciting time for women’s health clinicians. One development, the 9-valent human papillomavirus (HPV) vaccine, offers the potential to increase overall prevention of cervical cancer to over 90%. The other advance offers clinicians a cervical cancer screening alternative, HPV DNA testing, for primary cervical cancer screening. In this article, I underscore the data behind, as well as expert guidance on, these two important developments.
 

The 9-valent HPV vaccine expands HPV-type coverage and vaccine options for routine use
Joura EA, Giuliano AR, Iversen O, et al. A 9-valent vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–723.

Two HPV types, 16 and 18, cause the majority—about 70%—of cervical cancers. Vaccination against these types, as well as against types 6 and 11 that cause most condyloma, has been available in the United States since 2006, when the quadrivalent vaccine was approved by the US Food and Drug Administration (FDA).¹ Now, based on the results of Joura and colleagues’ randomized, double-blind phase 2b−3 study involving more than 14,000 women, the 9-valent vaccine (Gardasil 9, Merck, Whitehouse Station, New Jersey) has been recommended by the Advisory Committee on Immunization Practices (ACIP) as 1 of 3 HPV vaccines that can be used for routine vaccination.¹ (The other 2 vaccines include the bivalent [Cervarix, GlaxoSmithKline, Research Triangle Park, North Carolina] and quadrivalent [Gardasil, Merck]).

Compared with quadrivalent, does the 9-valent vaccine offer compelling additional protection?
The incidence rate of high-grade cervical intraepithelial neoplasia (CIN; ≥CIN 2 or adenocarcinoma in situ) related to the ­additional HPV types covered with the 9-valent vaccine (31, 33, 45, 52, and 58) was 0.1 per 1,000 ­person-years in the 9-valent group and 1.6 per 1,000 person-years in the quadrivalent group. This is equivalent to 1 case versus 30 cases of disease and translates to 96.7% efficacy (95% confidence interval [CI], 80.9−99.8) against these 5 additional high-risk HPV types. At 36 months, there was 1 case of high-grade cervical disease in the 9-valent group related to the 5 additional HPV types, compared with 20 cumulative cases in the quadrivalent group. At 48 months, there was 1 case in the 9-valent group and 27 cases in the quadrivalent group (FIGURE 1).

This expanded disease coverage means the vaccine has the potential to prevent an additional 15% to 20% of cervical cancers in addition to the potential to prevent 5% to 20% of other HPV-related cancers.³

The added HPV-type protection resulted in more frequent injection site reactions (90.7% in the 9-valent group vs 84.9% in the quadrivalent group). Pain, erythema, and pruritis were the most common reactions. While rare, events of severe intensity were more common in the 9-valent group. However, less than 0.1% of participants discontinued study vaccination because of a vaccine-related adverse event.

Study strengths and weaknesses
This was a well-designed prospective, randomized controlled trial. Follow-up was ­limited; however, this is typical for a clinical trial, and extended follow-up analyses have held up in other HPV vaccine trials; I don’t anticipate it will be any different in this case. The control arm in the case of this trial was the quadrivalent vaccine, as that is the routinely recommended vaccine, so it is not ethical to give placebo in this age-range population. The placebo study already was published,⁴ so Joura and colleagues’ results build on prior findings. 

What this EVIDENCE means for practice
In a widely vaccinated population, the 9-valent HPV vaccine has the potential to protect against an additional 20% of cervical cancers, compared with the quadrivalent vaccine. This is an important improvement in HPV infection and cervical disease prevention. Unfortunately, in the United States we still have very low coverage for the first dose of the HPV vaccine, and even lower coverage for the recommended 3-dose series. This is a big problem in the United States. Stakeholders and advocates need to figure out innovative ways to overcome the challenges of full vaccination for the patients in whom it’s routinely recommended—11- and 12-year-old girls and boys. HPV vaccination lags behind coverage for other vaccines recommended in this same age group—by 20% to 25%.³ US HPV vaccination rates are woefully low in comparison with such other countries as Australia, much of western Europe, and the UK. “If teenagers were offered and accepted HPV vaccination every time they received another vaccine, first-dose coverage for HPV would exceed 90%.”³

The ACIP recommends routine vaccination for HPV—with the bivalent, quadrivalent, or 9-valent vaccine—at age 11 or 12 years. They also recommend vaccination for females aged 13 through 26 years and males aged 13 through 21 years who have not been vaccinated previously. Vaccination is also recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously.¹

By the time I retire, I hope that the impact of protection against additional HPV infection types will be felt, with HPV vaccination rates improved and fewer women affected by the morbidity and mortality related to cervical cancer. As ObGyns, we want to do right by our patients; we need to embrace and continue to discuss the message of primary protection with vaccines that protect against HPV in order to overcome the mixed rhetoric patients and parents receive from other groups, including sensational media or political figureheads who might have an alternative agenda that is clearly not in the best interest of our patients.

HPV test alone is as effective as Pap plus HPV test for cervical disease screening
Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189–197.

The cobas (Roche Molecular Diagnostics, Pleasanton, California) HPV DNA test received FDA approval as a primary screening test for cervical cancer in women aged 25 and older in April 2015. This is a big paradigm shift from what has long been the way we screen women, starting with cytology. Simplistically, the thinking is that we start with the more sensitive test to enrich the population of women that might need additional testing, which might include cytology.

The FDA considered these end-of-study data by Wright and colleagues, which had not been publically published at the time, in its decision. With the Addressing the Need for Advanced HPV Diagnostics (ATHENA) 3-year prospective study, these investigators sought to address major unresolved issues related to HPV primary screening, such as determining which HPV-positive women should be referred to colposcopy and how HPV primary screening performs in the United States. Such a strategy long has been shown to be effective in large prospective European trials.

Details of the study
Three screening strategies were tested:

In all strategies, women who were referred to colposcopy and found not to have CIN 2 or greater were rescreened with both tests in 1 year and referred to colposcopy if the finding was ASC-US or higher-grade or persistently HPV-positive.

Of the 3 screening strategies, HPV primary in women 25 years and older had the highest adjusted sensitivity over 3 years (76.1%; 95% CI, 70.3–81.8) for the detection of CIN 3 or greater, with similar specificity as the cytology and hybrid strategies. In addition, the negative predictive value for not having clinically relevant disease for HPV primary was comparable to or better than the other 2 strategies (TABLE).⁵

Another important finding was that the number of colposcopies required to detect 1 case of cervical disease, although found to be significantly higher, was comparable for the HPV primary and cytology strategies (7.1 [95% CI, 6.4–8.0] for cytology vs 8.0 for HPV primary for CIN 2 or greater in women 25 years and older). For CIN 3 or greater, the number of colposcopies required to detect 1 case was 12.8 (95% CI, 11.7–14.5) for HPV primary versus 12.9 (95% CI, 11.5–14.8) for hybrid and 10.8 (95% CI, 9.4–12.6) for cytology.

What this EVIDENCE means for practice
These data indicate that HPV primary screening in women aged 25 and older is as effective as a hybrid screening strategy that uses cytology and cotesting in a patient older than 30 years. And HPV primary screening requires fewer overall screening tests to identify women who have clinically significant cervical disease.

Importantly, compared with a cytology-based strategy, the negative predictive value is quite high for HPV primary screening. Therefore, if someone has a negative HPV test result, the likelihood of that person actually having some sort of clinically relevant disease that day or in the next 3 years is incredibly low. And this is really what’s important for our patients who are getting screened for cervical cancer.

Interim guidelines support use of HPV testing alone or with the Pap smear
Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol. 2015;136(2):178–182.

The most recent set of consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors is the American Cancer ­Society/­American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology 2012 guidelines,⁶ which recommend cotesting as the preferred strategy in women aged 30 to 65 years. However, to address increasing evidence that HPV testing alone is an effective primary screening approach and how clinicians should adopt these findings in their practice, an expert panel convened to offer interim guidance. The panel was cosponsored and funded by the Society of Gynecologic Oncology (SGO) and ASCCP and included 13 experts representing 7 societies, including SGO, ASCCP, and the American College of Obstetricians and Gynecologists. This guidance can be adopted as an alternative to the updated 2012 ­recommendations until the next consensus guidelines panel convenes.

The panel considered a number of questions related to primary HPV testing and overall advantages and disadvantages of this strategy for screening.

Is HPV testing (for high-risk HPV [hrHPV] types) for primary screening as safe and effective as cytology-based screening?
The panel’s answer: Yes. A negative hrHPV test provides greater reassurance of low CIN 3 or greater risk than a negative cytology result. Because of its equivalent, or even superior, effectiveness—which has been demonstrated in the ATHENA study and several European randomized controlled screening trials^7,8—primary hrHPV screening can be considered as an alternative to current US cervical cancer screening methods.

A reasonable approach to managing a positive hrHPV result, advises the panel, is to triage hrHPV-positive women using a combination of genotyping for HPV 16 and 18 and reflex cytology for women positive for the 12 other hrHPV genotypes
(FIGURE 2).⁹

What is the optimal age to begin primary hrHPV screening?
The panel’s clinical guidance is not before age 25. This is a gray area right now, however, as there are concerns regarding the potential harm of screening at age 25 despite the increased detection of disease, particularly with regard to the number of colposcopies that could be performed in this age group due to the high incidence of HPV infection in young women. So the ideal age at which to begin hrHPV screening will need further discussion in future consensus guideline panels.

What is the optimal interval for primary hrHPV screening?
Prospective follow-up in the ATHENA study was restricted to 3 years. The panel advises that rescreening after a negative primary hrHPV screen should occur no sooner than every 3 years.

Outstanding considerations
The changeover from primary cytology to primary HPV testing represents a very different workflow for clinicians and laboratories. It also represents a different mode of screening for our patients, so patient education is essential. Many questions and concerns still need to be considered, for instance:

What this EVIDENCE means for practice
A move to the HPV test for primary screening represents a paradigm shift for clinicians and patients. Such a shift likely will be slow to occur, due to changes in clinical and laboratory workflow, provider and patient education, and systems issues. Also, there are a number of questions that still need to be answered. Primary hrHPV screening at age 25 to 29 years may lead to increased CIN 3 detection, but the impact of the increased number of colposcopies, integration for those women who already have been screened prior to age 25, and actual impact on cancer prevention need further investigation, the panel points out.

However, primary HPV screening can be considered as an alternative to current US cytology-based cervical cancer screening approaches. Over time, use of primary HPV screening appears to make screening more precise and efficient as it will minimize the number of abnormal cytology results that we would consider cytomorphologic manifestations of an active HPV infection that are not clinically relevant.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Two very recent significant advances in cervical disease prevention and screening make this an exciting time for women’s health clinicians. One development, the 9-valent human papillomavirus (HPV) vaccine, offers the potential to increase overall prevention of cervical cancer to over 90%. The other advance offers clinicians a cervical cancer screening alternative, HPV DNA testing, for primary cervical cancer screening. In this article, I underscore the data behind, as well as expert guidance on, these two important developments.
 

The 9-valent HPV vaccine expands HPV-type coverage and vaccine options for routine use
Joura EA, Giuliano AR, Iversen O, et al. A 9-valent vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–723.

Two HPV types, 16 and 18, cause the majority—about 70%—of cervical cancers. Vaccination against these types, as well as against types 6 and 11 that cause most condyloma, has been available in the United States since 2006, when the quadrivalent vaccine was approved by the US Food and Drug Administration (FDA).¹ Now, based on the results of Joura and colleagues’ randomized, double-blind phase 2b−3 study involving more than 14,000 women, the 9-valent vaccine (Gardasil 9, Merck, Whitehouse Station, New Jersey) has been recommended by the Advisory Committee on Immunization Practices (ACIP) as 1 of 3 HPV vaccines that can be used for routine vaccination.¹ (The other 2 vaccines include the bivalent [Cervarix, GlaxoSmithKline, Research Triangle Park, North Carolina] and quadrivalent [Gardasil, Merck]).

Compared with quadrivalent, does the 9-valent vaccine offer compelling additional protection?
The incidence rate of high-grade cervical intraepithelial neoplasia (CIN; ≥CIN 2 or adenocarcinoma in situ) related to the ­additional HPV types covered with the 9-valent vaccine (31, 33, 45, 52, and 58) was 0.1 per 1,000 ­person-years in the 9-valent group and 1.6 per 1,000 person-years in the quadrivalent group. This is equivalent to 1 case versus 30 cases of disease and translates to 96.7% efficacy (95% confidence interval [CI], 80.9−99.8) against these 5 additional high-risk HPV types. At 36 months, there was 1 case of high-grade cervical disease in the 9-valent group related to the 5 additional HPV types, compared with 20 cumulative cases in the quadrivalent group. At 48 months, there was 1 case in the 9-valent group and 27 cases in the quadrivalent group (FIGURE 1).

This expanded disease coverage means the vaccine has the potential to prevent an additional 15% to 20% of cervical cancers in addition to the potential to prevent 5% to 20% of other HPV-related cancers.³

The added HPV-type protection resulted in more frequent injection site reactions (90.7% in the 9-valent group vs 84.9% in the quadrivalent group). Pain, erythema, and pruritis were the most common reactions. While rare, events of severe intensity were more common in the 9-valent group. However, less than 0.1% of participants discontinued study vaccination because of a vaccine-related adverse event.

Study strengths and weaknesses
This was a well-designed prospective, randomized controlled trial. Follow-up was ­limited; however, this is typical for a clinical trial, and extended follow-up analyses have held up in other HPV vaccine trials; I don’t anticipate it will be any different in this case. The control arm in the case of this trial was the quadrivalent vaccine, as that is the routinely recommended vaccine, so it is not ethical to give placebo in this age-range population. The placebo study already was published,⁴ so Joura and colleagues’ results build on prior findings. 

What this EVIDENCE means for practice
In a widely vaccinated population, the 9-valent HPV vaccine has the potential to protect against an additional 20% of cervical cancers, compared with the quadrivalent vaccine. This is an important improvement in HPV infection and cervical disease prevention. Unfortunately, in the United States we still have very low coverage for the first dose of the HPV vaccine, and even lower coverage for the recommended 3-dose series. This is a big problem in the United States. Stakeholders and advocates need to figure out innovative ways to overcome the challenges of full vaccination for the patients in whom it’s routinely recommended—11- and 12-year-old girls and boys. HPV vaccination lags behind coverage for other vaccines recommended in this same age group—by 20% to 25%.³ US HPV vaccination rates are woefully low in comparison with such other countries as Australia, much of western Europe, and the UK. “If teenagers were offered and accepted HPV vaccination every time they received another vaccine, first-dose coverage for HPV would exceed 90%.”³

The ACIP recommends routine vaccination for HPV—with the bivalent, quadrivalent, or 9-valent vaccine—at age 11 or 12 years. They also recommend vaccination for females aged 13 through 26 years and males aged 13 through 21 years who have not been vaccinated previously. Vaccination is also recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously.¹

By the time I retire, I hope that the impact of protection against additional HPV infection types will be felt, with HPV vaccination rates improved and fewer women affected by the morbidity and mortality related to cervical cancer. As ObGyns, we want to do right by our patients; we need to embrace and continue to discuss the message of primary protection with vaccines that protect against HPV in order to overcome the mixed rhetoric patients and parents receive from other groups, including sensational media or political figureheads who might have an alternative agenda that is clearly not in the best interest of our patients.

HPV test alone is as effective as Pap plus HPV test for cervical disease screening
Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189–197.

The cobas (Roche Molecular Diagnostics, Pleasanton, California) HPV DNA test received FDA approval as a primary screening test for cervical cancer in women aged 25 and older in April 2015. This is a big paradigm shift from what has long been the way we screen women, starting with cytology. Simplistically, the thinking is that we start with the more sensitive test to enrich the population of women that might need additional testing, which might include cytology.

The FDA considered these end-of-study data by Wright and colleagues, which had not been publically published at the time, in its decision. With the Addressing the Need for Advanced HPV Diagnostics (ATHENA) 3-year prospective study, these investigators sought to address major unresolved issues related to HPV primary screening, such as determining which HPV-positive women should be referred to colposcopy and how HPV primary screening performs in the United States. Such a strategy long has been shown to be effective in large prospective European trials.

Details of the study
Three screening strategies were tested:

In all strategies, women who were referred to colposcopy and found not to have CIN 2 or greater were rescreened with both tests in 1 year and referred to colposcopy if the finding was ASC-US or higher-grade or persistently HPV-positive.

Of the 3 screening strategies, HPV primary in women 25 years and older had the highest adjusted sensitivity over 3 years (76.1%; 95% CI, 70.3–81.8) for the detection of CIN 3 or greater, with similar specificity as the cytology and hybrid strategies. In addition, the negative predictive value for not having clinically relevant disease for HPV primary was comparable to or better than the other 2 strategies (TABLE).⁵

Another important finding was that the number of colposcopies required to detect 1 case of cervical disease, although found to be significantly higher, was comparable for the HPV primary and cytology strategies (7.1 [95% CI, 6.4–8.0] for cytology vs 8.0 for HPV primary for CIN 2 or greater in women 25 years and older). For CIN 3 or greater, the number of colposcopies required to detect 1 case was 12.8 (95% CI, 11.7–14.5) for HPV primary versus 12.9 (95% CI, 11.5–14.8) for hybrid and 10.8 (95% CI, 9.4–12.6) for cytology.

What this EVIDENCE means for practice
These data indicate that HPV primary screening in women aged 25 and older is as effective as a hybrid screening strategy that uses cytology and cotesting in a patient older than 30 years. And HPV primary screening requires fewer overall screening tests to identify women who have clinically significant cervical disease.

Importantly, compared with a cytology-based strategy, the negative predictive value is quite high for HPV primary screening. Therefore, if someone has a negative HPV test result, the likelihood of that person actually having some sort of clinically relevant disease that day or in the next 3 years is incredibly low. And this is really what’s important for our patients who are getting screened for cervical cancer.

Interim guidelines support use of HPV testing alone or with the Pap smear
Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol. 2015;136(2):178–182.

The most recent set of consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors is the American Cancer ­Society/­American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology 2012 guidelines,⁶ which recommend cotesting as the preferred strategy in women aged 30 to 65 years. However, to address increasing evidence that HPV testing alone is an effective primary screening approach and how clinicians should adopt these findings in their practice, an expert panel convened to offer interim guidance. The panel was cosponsored and funded by the Society of Gynecologic Oncology (SGO) and ASCCP and included 13 experts representing 7 societies, including SGO, ASCCP, and the American College of Obstetricians and Gynecologists. This guidance can be adopted as an alternative to the updated 2012 ­recommendations until the next consensus guidelines panel convenes.

The panel considered a number of questions related to primary HPV testing and overall advantages and disadvantages of this strategy for screening.

Is HPV testing (for high-risk HPV [hrHPV] types) for primary screening as safe and effective as cytology-based screening?
The panel’s answer: Yes. A negative hrHPV test provides greater reassurance of low CIN 3 or greater risk than a negative cytology result. Because of its equivalent, or even superior, effectiveness—which has been demonstrated in the ATHENA study and several European randomized controlled screening trials^7,8—primary hrHPV screening can be considered as an alternative to current US cervical cancer screening methods.

A reasonable approach to managing a positive hrHPV result, advises the panel, is to triage hrHPV-positive women using a combination of genotyping for HPV 16 and 18 and reflex cytology for women positive for the 12 other hrHPV genotypes
(FIGURE 2).⁹

What is the optimal age to begin primary hrHPV screening?
The panel’s clinical guidance is not before age 25. This is a gray area right now, however, as there are concerns regarding the potential harm of screening at age 25 despite the increased detection of disease, particularly with regard to the number of colposcopies that could be performed in this age group due to the high incidence of HPV infection in young women. So the ideal age at which to begin hrHPV screening will need further discussion in future consensus guideline panels.

What is the optimal interval for primary hrHPV screening?
Prospective follow-up in the ATHENA study was restricted to 3 years. The panel advises that rescreening after a negative primary hrHPV screen should occur no sooner than every 3 years.

Outstanding considerations
The changeover from primary cytology to primary HPV testing represents a very different workflow for clinicians and laboratories. It also represents a different mode of screening for our patients, so patient education is essential. Many questions and concerns still need to be considered, for instance:

What this EVIDENCE means for practice
A move to the HPV test for primary screening represents a paradigm shift for clinicians and patients. Such a shift likely will be slow to occur, due to changes in clinical and laboratory workflow, provider and patient education, and systems issues. Also, there are a number of questions that still need to be answered. Primary hrHPV screening at age 25 to 29 years may lead to increased CIN 3 detection, but the impact of the increased number of colposcopies, integration for those women who already have been screened prior to age 25, and actual impact on cancer prevention need further investigation, the panel points out.

However, primary HPV screening can be considered as an alternative to current US cytology-based cervical cancer screening approaches. Over time, use of primary HPV screening appears to make screening more precise and efficient as it will minimize the number of abnormal cytology results that we would consider cytomorphologic manifestations of an active HPV infection that are not clinically relevant.

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at rbarbieri@frontlinemedcom.com Please include your name and city and state.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at rbarbieri@frontlinemedcom.com Please include your name and city and state.

Every year graduating medical students participate in the exciting, challenging, and anxiety-provoking process of applying to residency programs. After thousands of miles of travel, dozens of hotel overnight stays, and many interviews, the students are matched to their residency training site and begin specialty training. The first residency “Match” (conducted by the National Resident Matching Program) occurred in 1952 with 6,000 applicants and 10,400 available PGY-1 positions. In the 2014 Match, 34,270 applicants vied for 26,678 PGY-1 positions.¹

Of great interest to medical students and educators are the relative balance of applicants and residency positions in each specialty, and the magnitude of risk that a US medical student will not match to his or her chosen specialty. For students who have devoted years preparing for residency training in a chosen specialty the day they learn that they have not matched is heartbreaking, painful, and a test of their resilience. The Match does sponsor a supplemental offer and acceptance program that helps unmatched applicants to identify unfilled positions. This process helps unmatched applicants to continue their professional development without a delay.

When researching for this editorial, I consulted the National Resident Matching Program’s Results and Data 2014 Main Residency Match.¹ The TABLE shows the percentage of US medical school seniors who ranked a specialty as their only choice and did not match. The fields of neurosurgery, otolaryngology, plastic surgery, and orthopedic surgery had the greatest number of US medical school seniors (more than 17%) who ranked a specialty as their only choice and did not match in 2014. The fields of physical medicine and rehabilitation, dermatology, general surgery-categorical, obstetrics and gynecology, and radiation oncology had 6% to 11% of US seniors who ranked a specialty as their only choice not match in 2014. By contrast, almost all US applicants successfully matched in the fields of medicine-pediatrics, diagnostic radiology, anesthesiology, pathology, internal medicine-categorical, neurology, pediatrics-categorical, family medicine, emergency medicine, and psychiatry.

Clearly, obstetrics and gynecology is a popular career choice among medical students. Why might that be so?

Deeply meaningful relationships, continuity of care, plus surgical challenges
Students select a career in obstetrics and gynecology for many reasons. During their clinical experience in obstetrics and gynecology students often experience deeply meaningful relationships with patients at poignant life milestones, including conception, birth, and major surgery. In addition, students recognize that the field offers the opportunity to develop continuity relationships with patients and perform surgical procedures. Primary care specialists often develop deeply rewarding relationships with patients and their families that extend over decades, but they do not perform many surgical procedures. Procedure specialists, including general and orthopedic surgeons, perform hundreds of operations each year, but seldom have the opportunity to develop relationships with patients that last decades. Obstetrics and gynecology offers the combination of long-term continuity relationships with patients and training in surgical procedures.

Many other aspects of the field are attractive to students. Students report that their passion for the field was catalyzed by many factors and experiences, including:

Renew your enthusiasm for our field—mentor!
For practicing obstetricians and gynecologists the combined challenges of complex cases with unfortunate clinical outcomes, ever growing administrative burdens, and the difficulty of balancing work and personal-life may cause them to doubt the wisdom of choosing to train in the field. One of the best ways to erase these doubts is to mentor one of the about

1,250 newly minted physicians who will start their training in obstetrics and gynecology in the summer of 2015 or one of the approximately 1,300 US medical students who will apply to enter the field in 2016.

Medical students have a world of opportunity in front of them, with dozens of exciting career options. The fact that so many students select a career in our field is heartening. These students will become excellent obstetrician-gynecologistsand dedicate themselves to advancingthe health of the 150 million women in the United States. 
 

Would you select a career in obstetrics and gynecology again? Answer the Quick Poll on the home page and see how others have voted.

Why did you select a career in obstetrics and gynecology? Tell us at rbarbieri@frontlinemedcom.com Please include your name and city and state.

Endometriosis has always posed a treatment challenge. Take the early 19th Century, for example, before the widespread advent of surgery, when the disease was managed by applying leeches to the cervix. In fact, as Nezhat and colleagues note in their comprehensive survey of the 4,000-year history of endometriosis, “leeches were considered a mainstay in treating any condition associated with menstruation.”¹

Fast forward to the 21st Century, and the picture is a lot clearer, though still not crystal clear. The optimal approach to endometriosis depends on numerous factors, foremost among them the chief complaint of the patient—pain or infertility (or both). 

In this article—Part 2 of a 3-part series on endometriosis—the focus is on medical and surgical management of pain. Six experts address such questions as when is laparoscopy indicated, who is best qualified to treat endometriosis, is excision or ablation of lesions preferred, what is the role of hysterectomy in eliminating pain, and what to do about the problem of recurrence.

In Part 3, to be published in the June 2015 issue of OBG Management, ­endometriosis-associated infertility will be the topic of discussion.

In Part 1, 7 experts answer crucial questions on the diagnosis of endometriosis.

For a detailed look at the pathophysiology of endometriosis-associated pain, see “Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain,” by Kenneth A. Levey, MD, MPH, in this issue.

1. What are the options for empiric therapy?
One reason for the diagnostic delay for endometriosis, which still averages about 6 years, is that definitive diagnosis is achieved only through laparoscopic investigation and histologic confirmation. For many women who experience pain thought to be associated with endometriosis, however, clinicians begin empiric treatment with medical agents as a way to avert the need for surgery, if at all possible.

“There is no cure for endometriosis,” says John R. Lue, MD, MPH, “but there are many ways that endometriosis can be treated” and the impact of the disease reduced in a patient’s life. Dr. Lue is Associate Professor and Chief of the Section of General Obstetrics and Gynecology and Medical Director of Women’s Ambulatory Services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.

Among the medical and hormonal management options:

“For those using medical approaches, endometriosis-related pain may be reduced by using hormonal treatments to modify reproductive tract events, thereby decreasing local peritoneal inflammation and cytokine production,” says Pamela Stratton, MD. Because endometriosis is a “central sensitivity syndrome,” multidisciplinary approaches may be beneficial to treat myofascial dysfunction and sensitization, such as ­physical therapy. “Chronic pain conditions that overlap with endometriosis-associated pain, such as migraines, irritable bowel syndrome, or painful bladder syndrome should be identified and treated. Mood changes of depression and anxiety common to women with ­endometriosis-associated pain also warrant treatment,” she says.

Dr. Stratton is Chief of the Gynecology Consult Service, Program in Reproductive and Adult Endocrinology, at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland.

2. When is laparoscopy indicated?
When medical and hormonal treatments fail to control a patient’s pain, laparoscopy is indicated to confirm the diagnosis of endometriosis. During that procedure, it is also advisable to treat any endometriosis that is present, provided the surgeon is highly experi­enced in such treatment.

Proper treatment is preferable—even if it requires expert consultation. “No treatment and referral to a more experienced surgeon are better than incomplete treatment by an inexperienced surgeon,” says Ceana Nezhat, MD. “Not all GYN surgeons have the expertise to treat advanced endometriosis.” Dr. Nezhat is Director of the Nezhat Medical Center and Medical Director of Training and Education at Northside Hospital, both in Atlanta, Georgia.

Dr. Stratton agrees about the importance of thorough treatment of endometriosis at the time of diagnostic laparoscopy. “At the laparoscopy, the patient benefits if all potential sources of pain are investigated and addressed.” At surgery, the surgeon should look for and treat any lesions suspicious for endometriosis, as well as any other finding that might contribute to pain, she says. “For example, routinely inspecting the appendix for endometriosis or other lesions, and removing affected appendices is reasonable; also, lysis and, where possible, excision of adhesions is an important strategy.”

If a medical approach fails for a patient, “then surgery is indicated to confirm the diagnosis and treat the disease,” agrees ­Tommaso Falcone, MD.

“Surgery is very effective in treating the pain associated with endometriosis,” Dr. Falcone continues. Randomized clinical trials have shown that up to 90% of patients who obtain pain relief from surgery will have an effect lasting 1 year.⁶ If patients do not get relief, then the association of the pain with endometriosis should be questioned and other causes searched.” Dr. Falcone is ­Professor and Chair of Obstetrics and Gynecology at the Cleveland Clinic in Cleveland, Ohio.

The most common anatomic sites of implants
“The most common accepted theory for pathogenesis of endometriosis suggests that implants develop when debris from retrograde menstruation attaches to the pelvic peritoneum,” says Dr. Stratton.⁷ “Thus, the vast majority of lesions occur in the dependent portions of the pelvis, which include the ovarian fossae (posterior broad ligament under the ovaries), cul de sac, and the uterosacral ligaments.⁸ The bladder peritoneum, ovarian surface, uterine peritoneal surface, fallopian tube, and pelvic sidewall are also frequent sites. The colon and appendix are less common sites, and small bowel lesions are rare.”

“However, pain location does not correlate with lesion location,” Dr. Stratton notes. “For this reason, the goal at surgery is to treat all lesions, even ones that are not in sites of pain.”

3. How should disease be staged?
Most surgeons with expertise in treating endometriosis attempt to stage the disease at the time of initial laparoscopy, even though a patient’s pain does not always correlate with the stage of disease.

“The staging system for endometriosis is a means to systematically catalogue where lesions are located,” says Dr. Stratton.

The most commonly used classification system was developed by the American Society for Reproductive Medicine (ASRM). It takes into account such characteristics as how deep an implant lies, the extent to which it obliterates the posterior cul de sac, and the presence and extent of adhesions. Although the classification system is broken down into 4 stages ranging from minimal to severe disease, it is fairly complex. For example, it assigns a score for each lesion as well as the size and location of that lesion, notes Dr. ­Stratton. The presence of an endometrioma automatically renders the disease as stage III or IV, and an obliterated cul de sac means the endometriosis is graded as stage IV. 

“This system enables us to communicate with each other about patients and may guide future surgeries for assessment of lesion recurrence or the planning of treatment for lesions the surgeon was unable to treat at an initial surgery,” says Dr. Stratton.

“Women with uterosacral nodularity, fixed pelvic organs, or severe pain with endometriomas may have deep infiltrating lesions. These lesions, in particular, are not captured well with the current staging system,” says Dr. Stratton. Because they appear to be innervated, “the greatest benefit to the patient is achieved by completely excising these lesions.” Preoperative imaging may help confirm the existence, location, and extent of these deep lesions and help the surgeon plan her approach “based on clinical and imaging findings.”

“Severity of pain or duration of surgical effect does not correlate with stage or extent of disease,” Dr. Stratton says.⁹ “In fact, patients with the least amount of disease noted at surgery experience pain sooner, suggesting that the central nervous system may have been remodeled prior to surgery or that the pain is in part due to some other cause.¹⁰ This observation underscores the principle that, while endometriosis may initiate pain, the pain experience is determined by engagement of the central nervous system.”

For more information on the ASRM revised classification of endometriosis, go to http://www.fertstert.org/article/S0015-0282(97)81391-X/pdf.

4. Which is preferable—excision or ablation?
In a prospective, randomized, double-blind study, Healey and colleagues compared pain levels following laparoscopic treatment of endometriosis with either excision or ablation. Preoperatively, women in the study completed a questionnaire rating various types of pain using visual analogue scales. They then were randomly assigned to treatment of endometriosis via excision or ablation. Postoperatively, they again completed a questionnaire about pain levels at 3, 6, 9, and 12 months. Investigators found no significant difference in pain scores at 12 months.¹¹

Five-year follow-up of the same population yielded slightly different findings, however. Although there was a reduction in all pain scores at 5 years in both the excision and ablation groups, a significantly greater reduction in dyspareunia was observed in the excision group at 5 years.¹²

In an editorial accompanying the 5-year follow-up data, Dr. Falcone and a coauthor called excision versus ablation of ovarian, bowel, and peritoneal endometriosis one of the “great debates” in the surgical management of endometriosis.¹³

“When there is deep involvement of adjacent organs, there is general consensus that excision is best for optimal surgical outcome,” they write. “However, for disease involving the peritoneum alone, there are proponents for either option.”¹³

“This is a very controversial issue,” says Dr. Falcone, “and the debate can sometimes be somewhat inflammatory…. It is hard to understand how a comparative trial could even be accomplished between excision and ablation,” he adds. “In my experience, deep disease typically occurs on the pelvic sidewall over the ureter or in the cul de sac on the bowel or infiltrating the bladder peritoneum. Therefore, ablation would increase the risk of damaging any of these structures. With superficial disease away from critical structures, it should be fine to ablate. Everywhere else and with deep disease you need to excise or leave disease behind.”

“Endometriomas are a special situation,” Dr. Falcone says. “Excision of the cyst has been shown in randomized controlled trials (RCTs) to be associated with less risk of recurrence.¹⁴ Therefore, it should be the treatment of choice. However, in patients interested in future fertility, we must take into consideration the potential damage to ­ovarian reserve associated with excision.”

Endometriosis of the ovaries has unique manifestations. “My approach to ovarian cysts depends on their classification,” says Dr. Nezhat.¹⁵ In general, primary ­endometriomas (Type 1) are small, superficial cysts that contain dark “chocolate” fluid. They tend to be firmly adherent to the ovarian tissue and difficult to remove surgically.

Secondary endometriomas (Type 2) are follicular or luteal cysts that have been involved or invaded by cortical endometriotic implants or by primary endometrioma. Secondary endometriomas are further classified by the relationship between cortical endometriosis and the cyst wall. Type 2A endometriomas are usually large, with a capsule that is easily separated from ovarian tissue. Type 2B endometriomas have some features of functional cysts but show deep involvement with surface endometriosis. Type 2C endometriomas are similar, showing extensive surface endometrial implants but with deep penetration of the endometriosis into the cyst wall.¹⁵

“For Type 1 endometriomas, I biopsy the cyst to ensure the lesion is benign, then vaporize the endometrioma,” Dr. Nezhat says. “In cases of type 2A and 2B endometriomas, the cyst capsule is easily enucleated and removed. Type 2C endometriomas are biopsied as well and then I proceed with vaporizing the fibrotic area with a low-power energy source, such as neutral argon plasma, avoiding excessive coagulation and thermal injury.” Recent literature supports the idea of evaluation and biopsy of fibrotic endometriomas to confirm benign conditions, followed by ablation without compromising ovarian function.¹⁶

“Excision and ablation both have ­indications,” Dr. Nezhat asserts. “It depends on the location and depth of penetration of implants, as well as the patient’s ultimate goal. For example, if the patient desires future fertility and has endometriosis on the ovary, removal by excision could damage ovarian function. The same holds true for endometriosis on the fallopian tubes. It’s better in such cases to ablate.”

“Ablation is different from coagulation, which is not recommended,” Dr. ­Nezhat explains. “Ablation vaporizes the diseased area layer by layer, like peeling an onion, until the disease is eradicated. It is similar to ­dermatological skin resurfacing. Vaporization is preferable for endometriosis on the tubes and ovaries in patients who desire pregnancy. The choice between excision and ablation depends on the location, depth of penetration, and the patient’s desire for ­fertility.”

Either way, and regardless of the primary indication for surgery—pain versus infertility—a minimally invasive gynecologic surgeon is expected to have ability in performing both techniques, Dr. Nezhat says.

Endometriosis: 3 intraoperative videos The following videos have been provided by AAGL SurgeryU to compliment the content of this article regarding endometriosis. You can watch these videos, and more than 1,500 others, at AAGL.org/surgeryu. Laparoscopic excision of stage IV endometriosis Einarsson JI This case, originally presented as a SurgeryU live event, features a 41-year-old woman (G3P1) with a 3-year history of left-sided pelvic pain, deep dyspareunia, constipation, and dysmenorrhea. She also has infertility and is planning an IVF treatment shortly. On examination she was noted to have significant rectovaginal tenderness and nodularity. A pelvic MRI demonstrated a 3-cm irregular mass extending from the cervix into the cul-de-sac up to the left lateral pelvic sidewall. Abdominal wall endometriosis Hawkins E, Patzkowsky K, Lopez J This video demonstrates a typical presentation of abdominal wall endometriosis (AWE), also known as subcutaneous endometriosis or scar endometriosis. It is important for gynecologists to be familiar with this more uncommon form of the disease and its management. This video also demonstrates surgical management of advanced AWE involving the subcutaneous tissue, fascia, and rectus muscle. Laparoscopic excision of endometriosis in a 14-year-old patient with chronic pelvic pain Pendergrass M This video depicts the laparoscopic excision of endometriosis in a 14-year-old patient with chronic pelvic pain. The patient underwent menarche at age 11 and developed cyclic pelvic pain 6 months later. Due to the severity of the pain she has been unable to attend school for the past 2 months, and has stopped participating in sports. A diagnostic laparoscopy revealed red/brown superficial endometriosis lesions on the peritoneum in the posterior cul de sac, bilateral uterosacral ligaments, and bilateral broad ligaments.

5. Is hysterectomy definitive treatment for pain?
“Not necessarily,” says Dr. Nezhat. “Hysterectomy by itself doesn’t take care of endometriosis unless the patient has adenomyosis. If a patient has endometriosis, the first step is complete treatment of the disease to restore the anatomy. Then the next step might be hysterectomy to give a better long-term result, especially in cases of adenomyosis. Removal of the ovaries at the time of hysterectomy has to be individualized.”

“The implication that hysterectomy ‘cures’ endometriosis is false yet is stated in some textbooks,” says Dr. Nezhat. “Even at the time of hysterectomy, the first step should be complete treatment of endometriosis and restoration of anatomy, followed by the hysterectomy. Leaving endometriosis behind, believing it will go away by itself or not cause future issues, is a gross misperception.”

Removal of the ovaries at hysterectomy?
“There are few comparative studies on the long-term follow-up of patients who have undergone hysterectomy with or without removal of both ovaries,” says Dr. Falcone. “The conventional dogma has been that, in women undergoing definitive surgery for endometriosis, both ovaries should be removed, even if they are normal. I personally believe that this was the case because hysterectomy was often performed without excision of the endometriosis. So the uterus was removed and disease was left behind. In these cases, recurrent symptoms were due to persistent disease.”

“We reported our experience at the Cleveland Clinic with a 7-year follow-up,” Dr. Falcone continues. “Hysterectomy was performed with excision of all visible disease. Ovaries were conserved if normal and removed if they had disease. We looked at the reoperation-free frequency over time. In women undergoing hysterectomy with excision of visible disease but ovarian preservation, the reoperation-free percentages at 2, 5, and 7 years were 95%, 86%, and 77%, respectively, versus 96%, 91%, and 91% in those without ovarian preservation. So, overall, there was an advantage over time for removal of the ovaries. However, in the subset of women between ages 30 and 39 years, there was no difference in the long-term recurrence rate if the ovaries were left in. For this reason, in women under 40, we recommend keeping normal ovaries if all disease is removed.”¹⁷

6. Can the risk of postoperative recurrence be reduced?
“The main problem with surgery is the ­recurrence rate,” Dr. Falcone says. “Studies have shown that the recurrence rate of pain at 7 years may be as high as 50%.”¹⁷ Furthermore, “the recurrence of pain may not be associated with visualized endometriosis at laparoscopy.”

“Incomplete removal of lesions may be associated with an increase in pain after surgery,” says Dr. Stratton.¹⁸ “Incomplete removal of lesions may occur because of varying technical skill or specific lesion characteristics. The lesions may be difficult to remove because of their location. Lesions may not be recognized because their appearance can vary from subtle (red or clear or white) to classic (blue-black). The depth of the lesion may not be appreciated until surgery is under way and a surgeon may not be adequately prepared to treat deep lesions when they are identified.”

Another reason pain may persist or recur after surgery for endometriosis: Adenomyosis.¹⁹ “Adenomyosis appears as either diffuse or focal thickening of the junctional zone between the endometrium and myometrium of the uterus on T2 weighted magnetic resonance imaging (MRI),” says Dr. Stratton. “After excision of endometriosis, chronic pelvic pain is significantly more likely to persist in women who have a junctional zone thickness of more than 11 mm on MRI,” she says.

The frequent recurrence of pain after surgery for endometriosis means that the disease is a long-term challenge.

“Pelvic pain caused by endometriosis is a chronic problem that requires a multiyear management plan, involving both surgery and hormonal therapy,” says Robert L. ­Barbieri, MD. “To reduce the number of surgical procedures in the lifetime of a woman with endometriosis and pain, I suggest hormonal medical therapy following conservative surgery for endometriosis.”

“Definitive surgery, such as hysterectomy or hysterectomy plus bilateral ­ salpingo-oophorectomy (BSO) typicallyresults in prolonged symptom relief,” Dr. ­Barbieri says. “Following hysterectomy, hormonal therapy may not be needed. Following BSO, low-dose hormonal therapy is often needed to reduce the severity of menopausal symptoms.”

Dr. Barbieri is Editor in Chief of OBG Management; Chair of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, Massachusetts; and the Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School in Boston.

After surgical treatment of endometriosis associated with pain, Dr. Barbieri presents the patient with the following menu of hormonal options:

“I explain the side effects common with each approach and have the patient select what she determines to be her best option,” says Dr. Barbieri. “In my experience, conservative surgery followed by hormonal therapy is effective in more than 75% of women.”

“The evidence to support postoperative hormonal therapy is modest,” Dr. Barbieri notes. “The best evidence is available for use of the LNG-IUS, estrogen-progestin contraceptives, and GnRH agonists.”^20–22

In addition, “major professional societies have highlighted the option of postoperative hormonal therapy to reduce the risk of recurrent pain and repetitive surgical procedures in the future,” Dr. Barbieri says.^23,24

When pain recurs after surgery for endometriosis, it pays to consider what type of pain it is, says Dr. Barbieri.

“There are 2 major types of pain—nociceptive and neuropathic,” he says. “Nociceptive pain is caused by an injury, acute or chronic. Neuropathic pain is caused by ­‘activation’ of neural circuits, sometimes in the absence of an ongoing injury. Many women with endometriosis and chronic pain have both nociceptive and neuropathic pain. Consequently, it is important to consider the use of a multidisciplinary pain practice in the management of chronic pain syndromes. Multidisciplinary pain practices have special expertise in the management of neuropathic pain. Standard conservative surgical intervention is unlikely to improve pain caused by neuropathic mechanisms. Likewise, opioid analgesics are not recommended for the treatment of neuropathic pain.”
 

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Endometriosis has always posed a treatment challenge. Take the early 19th Century, for example, before the widespread advent of surgery, when the disease was managed by applying leeches to the cervix. In fact, as Nezhat and colleagues note in their comprehensive survey of the 4,000-year history of endometriosis, “leeches were considered a mainstay in treating any condition associated with menstruation.”¹

Fast forward to the 21st Century, and the picture is a lot clearer, though still not crystal clear. The optimal approach to endometriosis depends on numerous factors, foremost among them the chief complaint of the patient—pain or infertility (or both). 

In this article—Part 2 of a 3-part series on endometriosis—the focus is on medical and surgical management of pain. Six experts address such questions as when is laparoscopy indicated, who is best qualified to treat endometriosis, is excision or ablation of lesions preferred, what is the role of hysterectomy in eliminating pain, and what to do about the problem of recurrence.

In Part 3, to be published in the June 2015 issue of OBG Management, ­endometriosis-associated infertility will be the topic of discussion.

In Part 1, 7 experts answer crucial questions on the diagnosis of endometriosis.