Journal of the National Cancer Institute Advance Access originally published online on July 31, 2009
JNCI Journal of the National Cancer Institute 2009 101(16):1120-1130; doi:10.1093/jnci/djp205
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Published by Oxford University Press 2009.
ARTICLES |
Risk of Human Papillomavirus–Associated Cancers Among Persons With AIDS
Affiliations of authors: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD (AKC, EAE); Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA (MMM); State Serum Institute, Copenhagen, Denmark (RJB)
Correspondence to: Anil K. Chaturvedi, PhD, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS 7072, Rockville, MD 20852 (e-mail: chaturva{at}mail.nih.gov).
Background: Although risk of human papillomavirus (HPV)–associated cancers of the anus, cervix, oropharynx, penis, vagina, and vulva is increased among persons with AIDS, the etiologic role of immunosuppression is unclear and incidence trends for these cancers over time, particularly after the introduction of highly active antiretroviral therapy in 1996, are not well described.
Methods: Data on 499 230 individuals diagnosed with AIDS from January 1, 1980, through December 31, 2004, were linked with cancer registries in 15 US regions. Risk of in situ and invasive HPV-associated cancers, compared with that in the general population, was measured by use of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). We evaluated the relationship of immunosuppression with incidence during the period of 4–60 months after AIDS onset by use of CD4 T-cell counts measured at AIDS onset. Incidence during the 4–60 months after AIDS onset was compared across three periods (1980–1989, 1990–1995, and 1996–2004). All statistical tests were two-sided.
Results: Among persons with AIDS, we observed statistically significantly elevated risk of all HPV-associated in situ (SIRs ranged from 8.9, 95% CI = 8.0 to 9.9, for cervical cancer to 68.6, 95% CI = 59.7 to 78.4, for anal cancer among men) and invasive (SIRs ranged from 1.6, 95% CI = 1.2 to 2.1, for oropharyngeal cancer to 34.6, 95% CI = 30.8 to 38.8, for anal cancer among men) cancers. During 1996–2004, low CD4 T-cell count was associated with statistically significantly increased risk of invasive anal cancer among men (relative risk [RR] per decline of 100 CD4 T cells per cubic millimeter = 1.34, 95% CI = 1.08 to 1.66, P = .006) and non–statistically significantly increased risk of in situ vagina or vulva cancer (RR = 1.52, 95% CI = 0.99 to 2.35, P = .055) and of invasive cervical cancer (RR = 1.32, 95% CI = 0.96 to 1.80, P = .077). Among men, incidence (per 100 000 person-years) of in situ and invasive anal cancer was statistically significantly higher during 1996–2004 than during 1990–1995 (61% increase for in situ cancers, 18.3 cases vs 29.5 cases, respectively; RR = 1.71, 95% CI = 1.24 to 2.35, P < .001; and 104% increase for invasive cancers, 20.7 cases vs 42.3 cases, respectively; RR = 2.03, 95% CI = 1.54 to 2.68, P < .001). Incidence of other cancers was stable over time.
Conclusions: Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996–2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers.
| CONTEXT AND CAVEATS Prior knowledge Risk of human papillomavirus (HPV)–associated cancers is increased among persons with AIDS. Study design Retrospective study that used data from persons diagnosed with AIDS that were linked to cancer registry data to estimate risks for in situ and invasive HPV-associated cancers, including cancers of the anus, cervix, oropharynx, penis, vagina, and vulva. These risks were compared with those of the general population. Immunosuppression was investigated by use of the CD4 T-cell count at AIDS onset. Contribution Statistically significantly elevated risks for all HPV-associated cancers were observed among persons with AIDS. From 1996 (when highly active antiretroviral therapy was introduced) through 2004, a low CD4 T-cell count was associated with a statistically significantly increased risk of invasive anal cancer among men and incidence of anal cancer was statistically significantly higher in 1996–2004 than in 1990–1995. Implications Increased incidence of anal cancer was observed among persons with AIDS and it increased with increasing immunosuppression. Prolonged survival of persons with AIDS may be associated with their increased risk for some HPV-associated cancers. Limitations Information on risk factors, such as cigarette smoking, was not available. Persons with AIDS receive increased medical surveillance. One CD4 T-cell count measured at the onset of AIDS probably does not reflect fluctuations in immunosuppression over time. From the Editors
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Manuscript received October 1, 2008; revised May 26, 2009; accepted June 11, 2009.
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J Natl Cancer Inst 2009 101: 1101.