From the AGA Journals

Upper GI Cancer Risk Elevated in AIDS

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Gastroenterologists and the Cancer/AIDS Link

Over the 30 years of the HIV pandemic, the risk of cancer has been found to be significantly elevated in HIV-infected persons. These include the three “AIDS-defining” cancers (Kaposi Sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) and a variety of “non AIDS-defining” cancers. Gastroenterologists have been most likely to encounter either visceral KS or hepatocellular carcinoma.

Dr. Persson and her colleagues used large population-based HIV and cancer registries to describe an increased risk of two additional malignancies, esophageal cancer (both squamous cell and adenocarcinoma) and stomach cancer in persons with AIDS, in addition to mucosa-associated lymphomas (NHL). NHL decreased in the era of effective antiretroviral therapy, but esophageal and gastric cancers remained elevated, and none was correlated with CD4 count.

HIV-associated cancers are often attributed to an infectious etiology, which presumably in the setting of impaired immunity and increased inflammation leads to a greater risk of cancer. Both Epstein-Barr virus and Helicobacter pylori have been associated with gastric cancer and NHL, and the role they play in HIV-associated gastrointestinal malignancies needs to be further defined. Additionally, the high prevalence of tobacco and alcohol use in HIV patients may contribute to the risk of gastrointestinal malignancies.

Gastroenterologists clearly now need to be familiar with several malignancies in persons with HIV, including KS, NHL, and gastric and esophageal carcinoma. It remains unknown whether strategies such as earlier initiation of antiretroviral therapy, eradication of H. pylori, and reducing alcohol and tobacco use are effective in reducing the burden of cancer in HIV-infected persons.

COREY CASPER, M.D., M.P.H., is an associate member of the divisions of public health science and clinical research in the department of vaccine and infectious disease at the Fred Hutchinson Cancer Research Center, Seattle, and an associate professor of medicine, epidemiology, and global health at the University of Washington, Seattle. He also is medical director of infection control, Seattle Cancer Care Alliance.



AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

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