Male Circumcision Reduces Risk for HPV Infection in Female Partners

From Medscape Medical News

Emma Hitt, PhD

January 6, 2011 — Male circumcision appears to protect against high-risk human papillomavirus (HPV) infection in female partners, according to the findings of 2 randomized controlled trials carried out in rural Uganda.

Maria J. Wawer, MD, and Aaron A.R. Tobian, MD, from Johns Hopkins University, Baltimore, Maryland, and colleagues reported their findings from the studies, conducted in Rakai, Uganda, online January 7 in The Lancet.

According to the researchers, male circumcision has previously been linked to reduced HPV infection in men and to reduced risk for cervical neoplasia in women with circumcised partners. In the current study, HIV-negative men were randomly assigned to undergo circumcision immediately (intervention) or after a delay of 24 months (control). Their HIV-negative female partners were interviewed, and concurrent self-collected vaginal swabs were tested for high-risk HPV infection.

At 24 months after intervention, more than 1000 women remained enrolled in the study (544 in the intervention group and 488 in the control group). Results showed a significant reduction of 28% in the prevalence of high-risk HPV infection in female partners of circumcised men compared with the control group (27.8% vs 38.7%; prevalence risk ratio, 0.72; 95% confidence interval [CI], 0.60 - 0.85; P = .001).

In addition, male circumcision significantly reduced the incidence of high-risk HPV in women (20.7 vs 26.9 infections per 100 person-years; incidence rate ratio, 0.77; 95% CI, 0.63 - 0.93; P = .008). For women positive for all high-risk HPV genotypes, clearance of infection was also more likely in the intervention group (66% vs 59%; risk ratio, 1.12; 95% CI, 1.02 - 1.22; P = .014), although clearance of the HPV-16 genotype was lower.

The authors suggest that reduced penile HPV carriage may explain the way in which circumcision helps prevent HPV infection in women.

Study limitations include the inability to obtain samples from 20% of the women enrolled in each group because of temporary stock shortages. This reduced the sample size and the power of the study. In addition, study participants were HIV-negative and in steady partnerships; therefore, the results may only be applicable to low-risk, monogamous individuals. Finally, follow-up data were obtained annually, and so do not account for incident cases that occurred and resolved during the year.

"Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners," write Dr. Wawer, Dr. Tobian and colleagues.

According to the researchers, decreased incidence and prevalence of high-risk HPV infection is likely to reduce the long-term risk for cervical cancer for women with circumcised male partners. "However, our results indicate that protection is only partial; the promotion of safe sex practices is also important," they add.

In an editorial, Anna R. Giuliano, PhD; Alan G. Nyitray, PhD; and Ginesa Albero from the Department of Cancer Epidemiology and Genetics, H. Lee Moffitt Cancer Center, Tampa, Florida, recount the historical association of circumcision and reduced incidence of cervical cancer. Commending the work of Dr. Wawer, Dr. Tobian, and colleagues, they state that "these data, from the most rigorous of study designs, support original observations for a preventive role of male circumcision in cervical cancer."

They mention several caveats, however, to drawing this conclusion, "First, the reduction in high-risk HPV infection in women was limited to about 25%. Second, a clinical endpoint such as high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2/3) was not assessed. Third, clearance of HPV-16 was lower in the intervention group than in the control group."

The study was supported by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Fogarty International Center. One author reports receiving research funding from Roche Molecular Diagnostics, the company that manufactures the HPV genotyping test used in this study. The other study authors have disclosed no relevant financial relationships. Each of the editorialists has received financial support from Merck & Co, GlaxoSmithKline, and/or Roche.

Lancet. Published online January 7, 2011.