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Anal Cancer Rates Keep Climbing in US HIV Group Despite HAART
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Despite wide use of highly active antiretroviral therapy (HAART) since 1996, anal cancer rates in an HIV-infected US military population keep rising [1]. People who already had an AIDS diagnosis in this group ran more than a tripled risk of anal cancer.
Researchers from the San Diego Naval Medical Center and other institutions studied 4901 HIV-infected people seen at the naval center from 1985 through 2008. Just over half had documented HIV seroconversion dates. Most cohort members (92%) were male, 45% were African American, and 43% were Caucasian. Median age and CD4 count at HIV diagnosis were 28 years (interquartile range [IQR] 24 to 34) and 506 cells (IQR 350 to 676).
Defining anal cancer as histopathologically confirmed squamous cell carcinoma, the investigators counted 20 diagnoses from 1985 through 2008. The age-adjusted new anal cancer rate rose 5-fold from the pre-HAART era (1985-1995) to the HAART era, from 11 to 55 cases per 100,000 person-years. The age-adjusted rate climbed steadily in the HAART period, from 13.4 cases per 100,000 person-years in 1996-2000, to 51.1 cases in 2001-2005, and to 127.6 cases in 2006-2008.
The age-adjusted anal cancer rate also rose as duration of HIV infection increased, from 28.0 per 100,000 person-years during 0 to 5 years of infection, to 29.0 at 5 to 10 years, 63.1 at 10 to 15 years, and 347.6 after that. Only the rate after 15 years of infection significantly outstripped the rate during the first 5 years of infection (P < 0.0001). Eight of the 20 anal cancers diagnosed (40%) occurred in people infected with HIV more than 15 years.
Of the 20 people with newly diagnosed anal cancer, 19 (95%) were men in this largely male naval population. Median age of people with anal cancer stood at 41.6 years (IQR .6 to 46.0), 55% were white, 50% had a history of hepatitis B infection, 40% had gonorrhea, 30% had herpes simplex virus infection, 10% had syphilis, and 65% had any sexually transmitted infection. Infection with human papillomavirus (HPV), a sexually transmitted pathogen, can lead to anal squamous cell cancer, but the investigators did not have records on HPV in these people.
Median most-recent CD4 count before anal cancer diagnosis was 375 (IQR 217 to 509) and lowest-ever (nadir) CD4 count was 128 (IQR 50 to 255). Fifteen people (75%) were taking HAART when diagnosed with anal cancer, 40% had a viral load below 1000 copies, and 40% already had an AIDS diagnosis. Median duration of HIV infection stood at 5.9 years (IQR 4.1 to 9.6).
Multivariate statistical analysis adjusted for year of HIV diagnosis determined that people with an AIDS diagnosis had more than a tripled chance of anal cancer (hazard ratio [HR] 3.48 (95% confidence interval [CI] 1.33 to 9.12, P = 0.01). Every 50-cell higher nadir CD4 count cut the risk of anal cancer 15% (HR 0.85, 95% CI 0.73 to 0.98, P = 0.02). Another study at the 5th IAS Conference found a link between low CD4 count just before diagnosis of non-AIDS cancers of infectious origin and the risk of such cancers [2].
In the naval center study, a gonorrhea diagnosis more than doubled the risk of anal cancer, but this association fell short of statistical significance (HR 2.34, 95% CI 0.91 to 6.0, P = 0.08). Use of potent antiretroviral combinations in recent years had no impact on anal cancer risk.
The investigators noted that their study is limited by the low number of anal cancers diagnosed, lack of information of HPV coinfection, lack of data on sexual preference, and the possibility of important unmeasured factors. They speculated that, "as HIV patients are living longer, it may allow for sufficient time for anal cancer development, hence rates may continue to increase."
Although this study population consisted mostly of men, other work shows that women with HIV have a heightened risk of anal cancer. A Women's Interagency HIV Study analysis found that 10% of HIV-infected women in this US cohort have abnormal cell growth in anal tissue that may develop into anal cancer [3]. Another study found a higher risk of human papillomavirus-related anal cancer in men and women with HIV than in people without HIV [4]. And other research confirms that potent antiretrovirals do not protect people from anal cancer [5,6].
References
1. Crum-Cianflone N, Huppler Hullsiek K, Weintrob A, et al. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WEAB101.
2. Kesselring A, Gras L, Smit C, et al. Longer duration of exposure to immunodeficiency and detectable viremia both are risk factors for non-AIDS defining malignancies in HIV-1 infected patients on combination antiretroviral therapy. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WEAB104.
3. Hessol NA, Holly EA, Efird JT, et al. Anal intraepithelial neoplasia in a multisite study of HIV-infected and high-risk HIV-uninfected women. AIDS. 2009;23:59-70.
4. Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst. 2000;92:1500-1510.
5. Piketty C, Selinger-Leneman H, Grabar S, et al. Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy. AIDS. 2008;22:1203-1211.
6. Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97:425-432.
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