Abstract and Introduction
Abstract
Background: We investigated whether the reported lower incidence of prostate cancer in HIV-positive men is a result of confounding factors or reduced screening.
Methods: We conducted a cohort study of 17,424 HIV-positive and 182,799 HIV-negative men enrolled in Kaiser Permanente (KP). Subjects were followed from the first KP enrollment after January 01, 1996 for KP Northern California (KPNC) and January 01, 2000 for KP Southern California until the earliest of prostate cancer diagnosis, loss to follow-up, or December 31, 2007. Poisson regression was used to compare cancer rates by HIV status adjusting for age, race, smoking, alcohol/drug abuse, overweight/obesity, and diabetes. For the KPNC subset, we analyzed additional available data by HIV status on testosterone deficiency, and on prostate-specific antigen (PSA) tests as a proxy for cancer screening.
Results: The prostate cancer incidence rate was 102/100,000 person-years in HIV-positive men (n = 74 cases) and 131/100,000 person-years in HIV-negative men (n = 1195 cases), with an adjusted rate ratio of 0.73 (95% confidence interval: 0.57 to 0.92; P = 0.008). The reduced risk among HIV-positive men was greater for higher-stage cancers, which are less likely to be biased by screening differences than lower-stage cancers. In the KPNC subset, more HIV-positive (90.8%) than HIV-negative men (86.2%) received a PSA test by age 55 (P < 0.001). Decreased risk for HIV-positive men remained when examined only among those with a previous PSA test, and with adjustment for testosterone deficiency (rate ratio = 0.55; 95% confidence interval: 0.39 to 0.80; P = 0.001).
Conclusions: Prostate cancer incidence rates are lower in HIV-positive compared with HIV-negative men, which is not explained by screening differences or the risk factors evaluated.
Introduction
Combination antiretroviral therapy (ART) use has prolonged the lifespan of HIV-positive individuals, with more than half expected to be over 50 years of age in the United States by 2015. Men in this group are now increasingly diagnosed with prostate cancer, with an over 7-fold increase during 1991–2005. Despite rising incidence, there is no evidence of an elevated risk of prostate cancer, independent of age, among HIV-positive individuals compared with the general population. In fact, several studies have identified a 20%–50% lower age-adjusted risk of prostate cancer among HIV-positive compared with HIV-negative men. The reason for this reduced risk is unclear, but may be that there are differences in prostate cancer screening or prevalence of risk factors by HIV status. It is important to understand whether the lower risk of prostate cancer among HIV-positive men is due to less frequent screening, revealing a potential disparity that would need to be addressed; a biological effect, which would help advance our understanding of this common cancer; or a confounding bias that should be accounted for in future studies.
Comparisons of prostate cancer risk by HIV status need to consider differences in screening because most cases are asymptomatic at the time of diagnosis. In one of the only studies to evaluate use of prostate-specific antigen (PSA) testing among HIV-positive men, Shiels et al reported lower PSA testing rates in a cohort of low-income men with AIDS compared with external general population estimates. However, to the best of our knowledge, there are no studies that have evaluated prostate cancer risk by HIV status while accounting for screening practices in the same population.
The prevalence of prostate cancer risk factors may also differ by HIV status. Lower serum testosterone may be protective against prostate cancer, and HIV-positive men are more likely to experience hypogonadism for a variety of reasons, including pituitary impairment. HIV-positive individuals have a lower risk of other hormone-associated malignancies, including breast and thyroid cancers, lending support to the theory that hormone dysregulation contributes to decreased cancer risk in this population. Diabetes may also be an important mediator, given that it is more common among HIV-positive individuals taking certain protease inhibitors (PIs) or nucleoside reverse-transcriptase inhibitors and may have a protective effect against prostate cancer, possibly by reducing androgen receptor levels.
In this study, we evaluated prostate cancer incidence rates overall and by cancer stage among HIV-positive and HIV-negative men from the same health care system. We also aimed to determine whether the previously reported lower incidence rates of prostate cancer in HIV-positive men can be explained by reduced screening, mediating effects of testosterone deficiency or diabetes, or confounding effects of race/ethnicity or other risk factors.