In our study, men with AIDS appeared to have 50% lower risk of prostate cancer than men in the general population, which is consistent with previous studies that have also observed deficits in prostate cancer in HIV-infected men compared to the general population (2
). In the general U.S. population, PSA screening among men is very common (20
) and has contributed to a steep rise in prostate cancer incidence (14
). In contrast, we observed lower rates of PSA testing in a cohort of low income HIV-infected men in Baltimore, suggesting that PSA testing may be less common in men with HIV. Although previous studies have proposed biological explanations for the reduced risk of prostate cancer in men with AIDS (3
), our results suggest this deficit may be largely driven by differential PSA screening rates in the AIDS and general populations.
PSA screening patterns strongly determine diagnosed rates of prostate cancer. In the U.S., prostate cancer rates began to increase following the identification of PSA as a marker of prostate cancer in 1987 (21
) and peaked in 1992 (22
). Though rates have been stable since 1995, they remain substantially elevated in comparison to rates in 1986 (22
). It has been estimated that approximately 40% of prostate cancers diagnosed among men in the U.S. are detected through screening (19
). One study estimated that PSA screening has resulted in the diagnosis of prostate cancer in more than one million additional men in the last 20 years, the majority of whom were age 50 years or older (22
). Further, an estimated 67% of all screen-detected prostate cancers are overdiagnoses, meaning that these cancers would never have developed into symptomatic cancers (23
PSA screening may be more common among men in the U.S. general population than among HIV-infected men. In 2001, 57% of U.S. men age 40 years and older had a PSA test in the previous year (20
). This estimate is much higher, for example, than the age-standardized PSA testing rate of 22.7% per year observed in the JHHCC. Further, our estimates provide an upper bound of PSA screening in the JHHCC, because our data captured some PSA tests that might have been obtained for clinical indications rather than for screening in asymptomatic men. We speculate that the low rates of screening reflect clinicians’ perception that the historically poor prognosis of HIV-infected men would limit the test’s utility, coupled with challenges in addressing other medical and social issues in this population. Men in the JHHCC were receiving medical care, and PSA screening rates could be even lower among other HIV-infected populations that lacked access to care, e.g., due to lack of medical insurance. Though annual PSA testing rates in the JHHCC cohort remained lower than the general population, there was a two-fold increase from 2000 to 2008. Given this pattern, it is likely that the rate of PSA testing was less frequent in the years preceding 2000.
Our results imply that prostate cancer rates have been lower among men with AIDS largely because of the dramatic increase in PSA screening in the general population. Specifically, the deficit in prostate cancer that we observed among men with AIDS was limited to the PSA era. Indeed, PSA era incidence rates of prostate cancer in men with AIDS were actually slightly higher than in the general population when we used comparison rates from before the mass uptake of PSA screening. The explanation for this small excess is unclear, but it could reflect limitations in our approach of using historical rates or residual confounding by other factors for which we could not control in the comparison.
Further arguing that screening patterns largely explain the overall reduced risk of prostate cancer, we observed a significant deficit in localized and regional stage prostate cancers among men with AIDS, but no difference for distant stage prostate cancer compared to the general population. If the deficit in prostate cancer risk had a biological explanation, such as lower androgen levels or a direct effect of HIV itself, one would have predicted uniformly reduced risk across prostate cancer stages. Screen-detected cancers are more likely to be early stage and asymptomatic compared to clinically detected cancers (24
). Therefore, the disproportional deficit of localized/regional prostate cancer among men with AIDS adds support to the hypothesis that the difference is explained by low rates of screening. Likewise, the deficit in prostate cancer risk was greatest in groups that would have been least likely to have been screened, including injection drug users and men with very low CD4 cell counts. Additionally, we observed that the deficit in prostate cancers was seen across antiretroviral therapy calendar periods. Further arguing against a role of immune suppression, the risk of prostate cancer in immune suppressed transplant recipients is no different from the risk in the general population (5
Of final note, relative survival following prostate cancer diagnosis in men with AIDS was no worse than in prostate cancer patients in the general population. In men with AIDS, localized/regional prostate cancer was not associated with an increased risk of death (), similar to what is observed in the general U.S. population (25
). Even with lower rates of PSA screening, we did not find an elevated risk of advanced stage prostate cancer in men with AIDS, and the five-fold increase in mortality following distant stage prostate cancer in men with AIDS was similar to that reported for men in the general population (standardized mortality ratio=5.22) (25
). Thus, while the public health benefits of PSA screening in the general population are still under debate (26
), our results on mortality following a prostate cancer diagnosis do not suggest that men with AIDS are being harmed by the relatively low screening rates.
The main strength of our study was the use of nationally representative data from the HACM Study, which includes men with AIDS in the U.S. over the duration of the AIDS epidemic and before and after introduction of PSA screening. The main limitation of our study was our inability to assess PSA screening prevalence patterns for a larger and more representative HIV population or directly assess prostate cancer incidence in relation to screening. Further, though novel, the PSA testing results presented here from the JHHCC should be interpreted with caution. The JHHCC includes HIV-infected men that are primarily African American and low income, and is not representative of all HIV-infected men in the U.S; thus, PSA testing rates presented here may not be generalizable to all men infected with HIV.
In conclusion, there is a deficit in prostate cancers among American HIV-infected men, which is limited to local and regional stage cancers that are most likely to be detected by PSA screening. A sharp increase in prostate cancer incidence in the general population has largely been driven by widespread use of PSA screening, a practice that appears to be less frequently utilized for HIV-infected men. Combined, these factors suggest that the deficit in prostate cancer observed among HIV-infected men is largely an artifact due to differential PSA screening practices, and is likely not due to a protective effect of HIV against the development of prostate cancer. Further, it appears that the lack of PSA screening in HIV-infected men has not resulted in an increased risk of advanced stage prostate cancer or death.