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48th Annual ICAAC / IDSA 46th Annual Meeting
October 25-28, 2008
Washington, DC
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Lower CD4 Count With HIV Ups Risk of Anal Cancer in Case-Control Study
  48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
A CD4 count under 200 independently raised the risk of anal cancer more than 20 times in HIV-infected men at the Kaiser Permanente Oakland Medical Center [1]. No other variable correlated with anal cancer risk in this case-control study.
Recent studies trace a rising incidence of anal cancer among HIV-infected people since the dawn of potent antiretroviral combinations in London [2], California [3], and France [4], perhaps because these malignancies are more likely to be diagnosed as people live longer with HIV infection. But the correlation between immunity and risk of anal cancer remains poorly defined. The Oakland study involved all HIV-infected men diagnosed with anal cancer by biopsy or resection from January 1996 through December 2005. For each of them, the investigators randomly selected 3 HIV-infected men without anal cancer but matched for age and calendar month of the cancer diagnosis. All cases and controls had at least one CD4 count and one viral load measure in the 12 months before the cancer diagnosis.
The Kaiser team found 15 men with anal cancer. They had a significantly lower pre-diagnosis average CD4 count than the 45 controls (224 +/- 140 standard deviation versus 409 +/- 202 standard deviation, P < 0.001). All 15 men with anal cancer had AIDS, compared with 29 of the 45 controls (64%). But viral load did not differ significantly between cases and controls (average 8718 copies versus 9677 copies). Nor did duration of HIV infection differ much in the two groups (average 8.0 years versus 7.5 years). Eleven men with anal cancer (73%) were gay, compared with 29 controls (64%).
Univariate analysis found only one factor that raised the risk of anal cancer. A CD4 count under 200 made anal cancer 9.1 times more likely (95% confidence interval [CI] 1.9 to 43.0, P < 0.001). Multivariate analysis that adjusted for age, CD4 count, viral load, and duration of HIV infection determined that a sub-200 CD4 count raised the anal cancer risk 21.9 times (95% CI 2.0 to 235, P < 0.05).
The Oakland investigators believe their results "suggest that degree of immunosuppression is an important risk factor for anal cancer in HIV-infected men," especially when considering that all men with anal cancer in their cohort had AIDS compared with only two thirds of HIV-infected controls. The researchers proposed that "patients with HIV infection with low CD4 counts, particularly [gay men], should be screened for anal cancer." The screening threshold, they added, remains to be determined.
Anal cancer expert Joel Palefsky believes men and women at risk of anal intraepithelial neoplasia (AIN), a precursor of anal cancer, should be screened for that condition because local treatments for AIN are improving [5]. Palefsky argues that "all at-risk men and women should be screened for anal cancer by digital rectal exam, since real benefits accrue from early detection of cancer."
1. Cole PA, Leyden WA, Silverberg MJ. Risk factors for development of anal cancer in HIV-infected men. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2338.
2. Bower M, Powles T, Newsom-Davis T, et al. HIV-associated anal cancer: has highly active antiretroviral therapy reduced the incidence or improved the outcome? J Acquir Immune Defic Syndr. 2004;37:1563-1565.
3. Hessol NA, Pipkin S, Schwarcz S, et al. The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. Am J Epidemiol. 2007;165:1143-1153.
4. 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.
5. Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007;15:130-133 (http://www.iasusa.org/pub/topics/2007/issue4/130.pdf).