Human papillomavirus (HPV) infection may be a risk factor for HIV acquisition, according to findings from a Kenyan study.1 Young men who had HPV at the beginning of the four-year trial had a higher risk than uninfected men of subsequent HIV infection (hazard ratio, 1.6). The risk was elevated to an even greater extent among men infected with the HPV strains that can lead to cervical and other cancers (2.4).
If HPV infection increases the risk of HIV, then a vaccine for the former could be a valuable method of reducing the incidence of the latter. However, the literature on HIV incidence among men with HPV has been limited to men who have sex with men. To examine whether having HPV increases the chances of becoming infected with HIV among a broader sample of men, researchers analyzed data from a community-based, randomized trial focused on circumcision and HIV prevention.
Men were eligible for the trial, which was conducted between February 2002 and December 2006 in Kisumu, if they were aged 18–24, sexually active, uncircumcised and HIV-negative. The final sample consisted of 2,168 men who were monitored for 3.5 years. Participants were randomly chosen to undergo immediate circumcision or to have the procedure after two years (if they still desired it).
At the initial visit, men answered questions about their sexual behavior and social and demographic characteristics, gave blood and urine samples, and provided penile cell samples (from the glans and shaft) for HPV testing; they were also tested for several other STIs, including HIV. The polymerase chain reaction assay was used to detect and identify 44 strains of HPV, including those responsible for most cervical cancers (16 and 18) and most genital warts (6 and 11). Half of the respondents tested positive for HPV at the first survey visit; almost all of the positive test results were obtained from glans samples.
During the follow-up period, respondents were classified as having HIV once results were consistently positive across multiple office tests and lab tests. In these cases, the baseline blood sample was tested more rigorously to confirm that the infection occurred after the trial began. The investigators used Kaplan-Meier analyses to estimate the cumulative incidence of seroconversion and multivariate proportional hazard models to identify associations between risk factors and HIV infection.
In bivariate analyses, men had an increased likelihood of HPV infection if they earned a salary or were self-employed (odds ratio, 1.4 for each), did not bathe every day (2.2), had genital warts (5.0), were infected with herpes simplex virus type 2 (HSV-2), chlamydia or gonorrhea (1.3–2.2) or had had more than one lifetime sexual partner (1.5). The odds of testing positive for HPV were reduced among those who had at least a secondary education (0.7) or had used a condom with their most recent partner (0.8).
According to Kaplan-Meier estimates, 5.3% of men who had tested positive for HPV at baseline became infected with HIV over the course of the 42-month trial, compared with 4.0% of men who had tested negative. Among those who had had HPV-positive glans samples, the proportions were 5.8% and 3.7%, respectively.
In hazard models that adjusted for men's age, circumcision status, employment and HSV-2 infection, among other factors, men with HPV had a higher risk of HIV infection than did men who were HPV-negative (hazard ratio, 1.6). The risk of HIV acquisition was also elevated among men who had multiple strains of HPV (1.8), either of the two strains that cause most cervical cancers (2.4) or any of the four strains that together cause most cervical cancers and genital warts (1.9). A separate model that focused on glans samples revealed that earning a salary (2.4), having HSV-2 (1.8), and having any strain of HPV (1.8) were associated with an elevated risk of HIV infection, while age was negatively associated with HIV risk (0.8 per year). Results were generally similar in analyses limited to the first two years of the trial.
The researchers note that the study's strengths include its comprehensive assessments of HPV and HIV infection and its inclusion of a large cohort of men. However, they also acknowledge that the study had limitations: Men were not examined for lesions or other symptoms that may have made them more vulnerable to HIV, and the HPV, HSV-2 and behavioral data were cross-sectional rather than longitudinal. Nonetheless, given the potential benefits of reducing HIV risk by preventing HPV infection, the investigators conclude that the "results warrant…a randomized controlled trial to determine whether prophylactic HPV vaccination reduces the acquisition of HIV infection."—S. Ramashwar
REFERENCE
1. Smith JS et al., Increased risk of HIV acquisition among Kenyan men with human papillomavirus infection, Journal of Infectious Diseases, 201(11):1677– 1685.