www.hivandhepatitis.com

HIV Is a Major Contributor to Increase in Anal Cancer among U.S. Men

Increased incidence of anal cancer during the past 3 decades among men in the U.S. has been strongly influenced by the HIV epidemic, although a similar association was not observed for women, researchers reported in the October 5, 2012, advance edition of the Journal of the National Cancer Institute.

Anal cancer has continued to increase among people with HIV despite the advent of effective antiretroviral therapy (ART), as treatment has enabled them survive long enough to develop it. Anal dysplasia (abnormal cell growth) and cancer are often caused by oncogenic types of human papillomavirus (HPV). Unlike invasive cervical cancer, anal cancer is not classified as an AIDS-defining condition, even though both have the same cause.

Although anal cancer remains rare in the U.S. -- with an estimated 6230 total cases in 2012 -- incidence (new cases) has been steadily rising in the general population since 1940. It is not clear, however, how much recent increases may be attributable to HIV.

Meredith Shiels and colleagues from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute estimated the impact of the HIV epidemic on overall trends in anal cancer incidence in 17 U.S. states and metropolitan areas between 1980 -- the year before the first medical reports of AIDS -- and 2005.

The researchers obtained data on anal cancer in people with and without HIV/AIDS from the HIV/AIDS Cancer Match Study. They estimated the number of cases of anal cancer in people with HIV and used this to calculate the proportion of all anal cancer cases occurring in HIV positive people. Finally, they estimated trends over time in incidence rates of anal cancer in the general population overall and after excluding people with HIV.

Results

• Of the 20,533 estimated anal cancer cases reported during 1980-2005, 1665, or 8.1%, occurred in people with HIV.
• The proportion of anal cancer cases in people with HIV was highest during the most recent period of 2001-2005 -- well after the advent of effective ART -- at 28.4% among men and 1.2% among women.
• HIV infection did not have an impact on trends in anal cancer among women during 1980-2005, as incidence rates increased by 3.3% annually overall and by the same 3.3% after excluding cases in women with HIV.
• Among men, however, HIV had a strong impact during this period, with incidence rates increasing by 3.4% annually overall but by only 17% -- or half as much -- after excluding cases in men with HIV.
• Black men with anal cancer had more than double the prevalence of HIV infection compared with white men, likely reflecting the higher HIV prevalence among black men.
• The proportion of anal cancer cases among men with HIV was greater for squamous cell carcinomas than for adenocarcinomas (31.3% vs 2.7%), perhaps because squamous cell cancer is more often associated with HPV.

Based on these findings, the study authors concluded,"During 1980-2005, the increasing anal cancer incidence rates in the United States were strongly influenced by the HIV epidemic in males but were independent of HIV infection in females."

"A large proportion of U.S. males with anal cancer in recent years were HIV-infected," they continued. "Measures that would effectively prevent anal cancer in HIV-infected males could markedly reduce anal cancer rates at the population level."

Low CD4 cell counts are associated with increased risk of anal cancer, though it also occurs in HIV positive people with higher levels. "HIV-associated immunosuppression may contribute directly to development of anal cancer by impairing cell-mediated immune control of HPV," they suggested. "Though [ART] partially restores immune function, HIV therapy does not lead to the regression of anal cancer precursor lesions, and anal cancer incidence has increased in the [combination ART] era."

They noted that not all anal cancers in HIV positive people are necessarily attributable to HIV infection itself, as men who have sex with men (MSM) are at increased risk even without HIV. But gay men with HIV have a higher prevalence of anal dysplasia and a 10-fold increased risk of anal squamous cell carcinoma compared with HIV negative MSM.

"Two cancer prevention strategies have been suggested for reducing the burden of anal cancer: HPV vaccination and anal Papanicolaou (Pap) testing," the researchers wrote. "Widespread vaccination against HPV 16 and 18 will reduce the burden of HPV-associated cancers, including anal cancer...However, vaccine uptake remains low, and because most anal cancers in the general population occur among those aged 60 years or older, any benefits of HPV vaccination on anal cancer rates will not be observed for decades."

"Based on the success of the Pap test for cervical cancer screening, use of a similar Pap test for detection of anal cancer precursors could potentially reduce anal cancer incidence," they continued. "Anal cancer screening may be cost-effective in HIV-infected and HIV-uninfected MSM, and New York State guidelines recommend anal Pap testing for certain HIV-infected individuals. However, anal Pap testing has not been shown to reduce anal cancer incidence or mortality, and a recent study concluded that more information is needed about the natural history of anal cancer and the progression rates of high-grade anal intraepithelial lesions before anal cancer screening in high-risk groups should be implemented."

10/10/12

Reference

MS Shiels, RM Pfeiffer, AK Chaturvedi, et al. Impact of the HIV Epidemic on the Incidence Rates of Anal Cancer in the United States. Journal of the National Cancer Institute. October 5, 2012 (Epub ahead of print).

Other Source

Journal of the National Cancer Institute. HIV Helps Explain Rise of Anal Cancer in US Males. Press release. October 5, 2012.