HIV-positive gay or bisexual men in the Netherlands became infected with high-risk human papillomavirus (HPV) in both the anus and penis at a higher rate than HIV-negative gays.1 Anal HPV cleared naturally in HIV-positive men more slowly than in HIV-negative men.
High-risk HPV types can cause anal cancer in men and women, penile cancer in men, cervical cancer in women, other cancers, and genital warts. In the United States and many other countries, HPV gets passed from person to person during sex more than any other virus or bacterium.2 Gay or bisexual men -- especially those with HIV -- run a higher risk of HPV infection and anal cancer than other men. There are vaccines that prevent infection with the HPV types most likely to cause cancer, but in the United States few young gay men get these vaccines.3 (See "Few Young Gay/Bisexual Men in U.S. Getting Important Vaccine Against HPV" in this issue of HIV Treatment Alerts.)
To learn more about rates of cancer-causing anal and penile HPV in HIV-positive versus HIV-negative gay and bisexual men, researchers in Amsterdam conducted this 2-year study.
How the Study Worked
Researchers invited gay or bisexual men in Amsterdam to join the 2-year study. Men could be HIV-positive or HIV-negative. At an initial study visit then every 6 months, men completed a questionnaire and used swabs to collect separate samples from the anus and the penis. Technicians used these samples to determine whether the anus or penis of each man carried one of 12 high-risk (cancer-causing) HPV types.
The researchers defined high-risk HPV incidence (the new-infection rate) as a positive test for a specific HPV type after two consecutive negative results for that HPV type at previous study visits. They defined HPV clearance as a positive test for a specific HPV type at one visit followed by negative results for that HPV type at the next two visits.
The investigators used standard statistical methods to calculate HPV incidence and clearance in HIV-positive versus HIV-negative men. These analyses looked at incidence and clearance of the two most dangerous HPV types (HPV-16 and HPV-18) and incidence and clearance of all 12 high-risk HPV types combined. The researchers also compared incidence and clearance in four groups: (1) HIV-negative men, (2) HIV-positive men with a lowest-ever CD4 count above 350, (3) HIV-positive men with a lowest-ever CD4 count between 200 and 350, and (4) HIV-positive men with a lowest-ever CD4 count below 200.
What the Study Found
The study involved 750 men who have sex with men, 302 (40%) of whom had HIV infection at their first study visit. Most men (83%) made all five scheduled study visits over the 2-year study period. HIV-infected men were significantly older than HIV-negative men (median 46 versus 38 years), and HIV-positive men had a higher median number of lifetime sex partners (300 versus 100). ("Significant" means a statistical test determined that these differences cannot be explained by chance.)
At the first study visit, a significantly higher proportion of HIV-positive men had anal high-risk HPV infection (63% versus 46% in HIV-negative men). And a significantly higher proportion of HIV-positive men had high-risk penile HPV infection at the first visit (31% versus 17%). Among 705 men who had at least three study visits, 652 (92%) picked up high-risk anal HPV and 419 (59%) picked up high-risk penile HPV. Compared with HIV-negative men, HIV-positive men had a higher incidence of 11 of 12 high-risk HPV types in the anus and 11 of 12 high-risk HPV types on the penis.
Statistical analysis determined that HIV-positive men had a 90% higher incidence of anal HPV-16* than HIV-negative men and a 60% higher incidence of all anal high-risk HPV types combined (Figure 1). This type of analysis considers several HPV risk factors at the same time, so the researchers can be confident that HIV itself explained the higher HPV incidence in these gay men. The same kind of statistical analysis determined that HIV-positive men had a 40% higher incidence of all high-risk HPV types combined on the penis.
Next the researchers calculated high-risk HPV clearance rates in men who had a high-risk HPV type detected in anal or penile samples. (Clearance is the natural disappearance of an HPV type.) In anal samples, men with HIV cleared 10 of 12 high-risk HPV types significantly less often than HIV-negative men. Statistical analysis that considers several HPV risk factors at the same time determined that HIV-positive men had 30% lower clearance of all anal high-risk HPV types combined. In contrast, HIV-positive men cleared high-risk HPV from the penis at the same rate as HIV-negative men or more often than HIV-negative men.
Incidence and clearance of high-risk anal or penile HPV did not differ between HIV-positive men with different lowest-ever CD4 counts.
What the Results Mean for You
This large 2-year comparison of HIV-positive and negative men who have sex with men found higher rates of new anal and penile human papillomavirus (HPV) in the men with HIV. And gay men with HIV naturally cleared anal HPV at a lower rate than gay men without HIV. Statistical analysis showed that HIV infection by itself -- independently of other HPV risk factors -- explained the higher HPV infection and clearance rates in these gay men. This means HIV-positive and negative men may have the same kind of sex and the same frequency of sex, yet HIV-positive men will still have a higher rate of new anal and penile HPV infection.
HPV can cause cancer of the anus or penis in men, cancer of the anus or cervix in women, other cancers in men and women, and genital warts in men or women. There are no drugs to treat HPV infection itself. Warts caused by HPV can be treated,4 and anal cell changes that lead to anal cancer can be treated.5 U.S. health authorities recommend regular Pap tests for HIV-positive women to detect HPV-related cervical cell changes that can lead to cervical cancer;4 and certain changes can trigger early treatment. But experts disagree on whether a similar strategy will prevent anal cancer.6
Vaccination can prevent infection with cancer-causing HPV types, but the vaccines must be given early in life because it's so easy to pick up HPV infection once a person starts having sex. In the United States, health authorities recommend HPV vaccination for all boys and girls starting at age 11 or 12.2 HIV-positive men and women up to age 26, and gay or bisexual men up to age 26, should get the HPV vaccine if they have not already done so or have not completed the three doses required.2
For men, circumcision lowers the risk of picking up HPV during sex.4 Wearing a latex condom during sex prevents picking up or spreading HPV and other sexually transmitted infections.4 Not sharing sex toys can also protect a person from HPV infection.4
* HPV-16 is the HPV type most often linked to anal cancer.
- Mooij SH, van Santen DK, Geskus RB, et al. The effect of HIV infection on anal and penile human papillomavirus incidence and clearance: a cohort study among MSM. AIDS. 2016;30:121-132.
- Centers for Disease Control and Prevention. Human papillomavirus (HPV). Questions and answers. 2015.
- Cummings T, Kasting ML, Rosenberger JG, Rosenthal SL, Zimet GD, Stupiansky NW. Catching up or missing out? Human papillomavirus vaccine acceptability among 18- to 26-year-old men who have sex with men in a U.S. national sample. Sex Trans Dis. 2015;42:601-606.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2014.
- Weis SE. Current treatment options for management of anal intraepithelial neoplasia. Onco Targets Ther. 2013;6:651-665.
- Mascolini M. Anal cancer screening approach awaits more data and clinical expertise. RITA. 2013;18(2):39-48.