Risk of human papillomavirus-associated cancers among persons with AIDS

Abstract

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.

Figure 1

Risk of in situ human papillomavirus (HPV)–associated cancers among persons with AIDS, according to time relative to AIDS onset. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for in situ HPV-associated cancers are presented across the following five risk periods relative to AIDS onset: a = 60–25 months before AIDS; b = 24–7 months before AIDS; c = 6 months before to 3 months after AIDS (the AIDS onset period); d = 4–27 months after AIDS; and e = 28–60 months after AIDS. The AIDS onset period was excluded from trend analyses. P_trend values were calculated by use of Poisson regression. All statistical tests were two-sided.

Figure 2

Risk of invasive human papillomavirus (HPV)–associated cancers among persons with AIDS, according to time relative to AIDS onset. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for invasive HPV-associated cancers are presented across the following five risk periods relative to AIDS onset: a = 60–25 months before AIDS; b = 24–7 months before AIDS; c = 6 months before to 3 months after AIDS (the AIDS onset period); d = 4–27 months after AIDS; and e = 28–60 months after AIDS. The AIDS onset period was excluded from trend analyses. P_trend values were calculated by use of Poisson regression. All statistical tests were two-sided.

Figure 3

Incidence of in situ and invasive human papillomavirus (HPV)–associated cancers in the 4- to 60-month period after AIDS, according to CD4 T-cell count at AIDS onset. Incidence of HPV-associated cancers per 100 000 person-years is shown according to the following five CD4 T-cell count categories: a = 0–99 cells per cubic millimeter; b = 100–199 cells per cubic millimeter; c = 200–299 cells per cubic millimeter; d = 300–399 cells per cubic millimeter; and e = 400–499 cells per cubic millimeter. Analyses were restricted to persons diagnosed with AIDS during the era of highly active antiretroviral therapy (1996–2004). A) Anal cancer among men. B) Anal cancer among women. C) Cervical cancer. D) Oropharyngeal cancer. E) Cancer of the penis. F) Cancer of the vagina or vulva. Broken lines = in situ cancers; solid lines = invasive cancers. The number of cancer patients in each CD4 T-cell count category is also shown. Error bars = 95% confidence intervals.