When HIV-negative men are circumcised, it provides protection against transmission of human papillomavirus (HPV) to HIV-negative women. However, the protection is only partial and the study authors note that it is also important to observe safe sex practices. The study is by the Rakai Health Sciences Program in Uganda, and reported by Drs. Aaron Tobian and Maria Wawer, Johns Hopkins University, Baltimore, MD, USA.
Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. As infection with high-risk HPV is a necessary precondition for cervical cancer, the potential efficacy of male circumcision for the prevention of cervical neoplasia can best be assessed in randomised controlled trials of male circumcision that measure incidence, prevalence, and clearance of high-risk HPV infection in female partners of men randomly assigned to male circumcision immediately or after a delay. In this study, the authors assessed the effectiveness of male circumcision to prevent high-risk HPV infection in HIV-negative female partners of HIV-negative men who were enrolled in two randomised controlled trials of male circumcision in Rakai, Uganda.
Two parallel but independent randomised controlled trials of male circumcision, enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were then tested for high-risk HPV. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial.
During the trial, 18 men in the control group underwent male circumcision elsewhere, and 31 in the intervention group did not undergo male circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (28%) women in the intervention group and 189 (39%) in the control group had high-risk HPV infection, which, after statistical analysis, mean those not circumcised had a 28% higher risk of being infected with HPV. During the trial, incidence of new high-risk HPV infection in women was lower in the intervention group than in the control group (20•7 infections vs 26•9 infections per 100 person-years; translating to a 23% lower infection rate).
The authors say: "Circumcision of adolescent and adult men in a rural Ugandan population significantly reduced the prevalence and incidence of both low-risk and high-risk HPV infections and increased clearance of high-risk HPV infections in their female partners."
They conclude: "Along with previous trial results in men, these findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing heterosexually acquired high-risk and low-risk HPV infections in men who do not have HIV and in their female partners. However, our results indicate that protection is only partial; the promotion of safe sex practices is also important."
In a linked Comment, Dr Anna R Giuliano, Department of Cancer Epidemiology and Genetics, H Lee Moffitt Cancer Center, Tampa, FL, USA, and colleagues say: "Recent findings add important evidence for the promotion of male circumcision in countries without well-established programmes for cervical screening. Additional interventions to reduce HPV infection, such as provision of vaccines for HPV prevention, will be essential to reduce invasive cervical cancer worldwide. Male circumcision is associated with slight reductions in high-risk HPV, while licensed HPV vaccines protect with high effectiveness against only a limited number of HPV types. Therefore, the two interventions are likely to have important synergistic effects."
Dr Aaron Tobian, Johns Hopkins University, Baltimore, MD, USA. T) +1 443 287-0527 E) atobian1@jhmi.edu
Dr Anna R Giuliano, Department of Cancer Epidemiology and Genetics, H Lee Moffitt Cancer Center, Tampa, FL, USA. T) +1 813.454.9044 E) anna.giuliano@moffitt.org
Journal
The Lancet