Circumcision of HIV-negative men reduces cervical cancer risk for female partners

Circumcising men modestly reduces the risk of transmitting types of human papillomavirus associated with cervical and anal cancer to women, an analysis of two randomised trials of male circumcision has shown.

The findings, published in The Lancet on January 7, come from two trials conducted in the Rakai region of Uganda, in which HIV-negative men were circumcised to test whether it reduced their risk of HIV infection.

Those studies showed that circumcision reduced the risk of HIV infection, and as a consequence of these and other studies, the World Health Organization and UNAIDS now recommend that circumcision of HIV-negative men should form part of national HIV prevention programmes in sub-Saharan Africa.

The studies also showed that circumcision reduced the risk of men acquiring high-risk forms of human papilloma virus by around 35%, that is, forms of human papilloma virus associated with the development of cervical cancer in women, and anal cancer in both sexes.

Circumcision also reduced the risk of genital ulcer disease, trichomonas vaginalis and bacterial vaginosis in the female partners of the circumcised men.

Aaron Tobian and Maria Wawer of Johns Hopkins University, Baltimore, who led the Rakai circumcision study with Professor Ron Gray, conducted a further analysis to determine whether circumcision reduced the risk of acquiring high-risk types of human papilloma virus for female partners of circumcised men.

The design of the studies has been described previously. For the purposes of evaluating the effect of circumcision on acquisition and clearance of HPV infection in women, 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.

After 24 months of follow-up, data were available for 544 women in the intervention group and 488 in the control group, showing that 27.8% of women in the intervention group and 38.7% of women in the control group had acquired a high-risk form of human papilloma virus.

The incidence during the study was 20.7 per 100 person-years of follow-up in the intervention group, compared to 26.9 infections per 100 person years in the control group. This represents a 23% reduction in the risk of acquiring high-risk HPV (incidence rate ratio 0.77, 95% confidence intervals 0.63-0.93, p=0.008).

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."