STD Quarterly
Research update: Male circumcision reduces risk of genital herpes and HPV infection
Data indicate circumcision had no effect on risk of syphilis
Findings from two parallel clinical trials in Rakai, Uganda, indicate that heterosexual men who undergo medical circumcision can significantly reduce their risk of acquiring two common sexually transmitted diseases (STDs): herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV).1
The newly published research follows earlier investigations that found that circumcision decreases a man's risk of acquiring HIV infection through heterosexual intercourse by more than half.2-4
"Medically supervised adult male circumcision is a scientifically proven method for reducing a man's risk of acquiring HIV infection through heterosexual intercourse," says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease (NIAID), a funder for the investigation. "This new research provides compelling evidence that circumcision can provide some protection against genital herpes and human papillomavirus infections as well."
Data could impact counseling
The data could be a major factor for how health providers counsel patients and parents on circumcision, say Matthew Golden, MD, MPH, and Judith Wasserheit, MD, MPH, in a companion commentary.5 Circumcision rates have been declining in the United States and are lowest among black and Hispanic patients, two groups with the highest rates of HIV, herpes, and cervical cancer,6 they observe.
"We already knew that circumcision can decrease men's HIV risk by 60%," says Golden, director of the STD Control Program for Public Health — Seattle & King County. "Now we know that male circumcision reduces men's risk of herpes by 25% and of human papillomavirus by a third."
With the new data in hand, providers who care for pregnant women and infants have a responsibility to let mothers and fathers know that circumcision could help protect their sons from HIV, HPV, and HSV, all of which cannot currently be cured, notes Wasserheit, vice chair of the University of Washington Department of Global Health.
Review the research
To perform the current study, scientists at the Rakai Health Sciences Program in Uganda collaborated with researchers at the Johns Hopkins University Bloomberg School of Public Health in Baltimore; Makerere University in Kampala, Uganda; and NIAID's Division of Intramural Research.
The scientists used results from two trials, one funded by NIAID and the other by the Bill & Melinda Gates Foundation, which together enrolled 3,393 uncircumcised men between ages 15 and 49 who initially tested negative for HIV and HSV-2. The men were assigned at random to one of two study groups: an intervention group of 1,684 men who received immediate circumcision performed by trained medical professionals in an outpatient setting, and a control group of 1,709 men who were circumcised after a 24-month delay. Volunteers were evaluated at six, 12 and 24 months for HSV-2 and syphilis infection; additionally, a subgroup of 697 volunteers (352 men from the intervention group and 345 from the control group) was evaluated for HPV infection at enrollment and at 24 months.
In an analysis of the effect of circumcision on HSV-2 acquisition across both studies, the researchers found the cumulative probability of HSV-2 infection was lower among those men who received immediate circumcision (7.8%) than among those in the control group who were circumcised at 24 months (10.3%). Overall, the scientists found that medically supervised circumcision reduced the men's risk of HSV-2 infection by 28%.
The combined results from both trials demonstrated a 35% reduction in HPV prevalence among men in the intervention group. In evaluating a subgroup of volunteers at 24 months, high-risk HPV strains associated with certain cancers were detected in 42 of 233 men in the intervention group and in 80 of 287 men in the control group.
Researchers note that circumcision did not affect the incidence of syphilis. At 24 months, syphilis was detected in 50 men in the intervention group and 45 members of the control group. The biological reasons why circumcision may reduce the risk of HSV-2 and HPV infection, but not syphilis, are not entirely known. HSV-2 and HPV can proliferate in epithelial cells found in the surface skin of the penis; the foreskin might facilitate virus entry into those cells, the researchers note. When circumcision is performed, it might reduce the risk of epithelial infection, they surmise.1
The new findings, in conjunction with those of previous trials, indicate that circumcision should now be accepted as an efficacious intervention for reducing heterosexually acquired infections with HSV-2, HPV, and HIV in adolescent boys and men, the researchers note. "However, it must be emphasized that protection was only partial, and it is critical to promote the practice of safe sex," the researchers advise.1
Scientists next plan to analyze additional data collected in the Rakai trials to assess the impact of male circumcision on transmission of HPV to female sexual partners.
More work to follow
More evidence of circumcision's positive effects continues to emerge from the research field. Findings from two studies presented at the 104th Annual Scientific Meeting of the American Urological Association (AUA) suggest that adult circumcision reduces the risk of contracting the human immunodeficiency virus and the risk of coital injury without reducing pleasure or causing sexual dysfunction.7,8
"These are important reports which support the concepts that circumcision does not interfere with sexual function and that circumcision is an important element of HIV prevention in sub-Saharan Africa," says Ira Sharlip, MD, an AUA spokesman. "At the same time, it should be emphasized that circumcision must be combined with other techniques of HIV prevention, such as safe sex and voluntary testing; it is not sufficient to rely on circumcision alone to prevent HIV transmission."
To keep up with the latest information on male circumcision, providers should visit the Clearing-house on Male Circumcision for HIV Prevention web site, www.malecircumcision.org. The web site was launched in February 2009 through a joint effort by the World Health Organization, Joint United Nations Programme on HIV/AIDS, AIDS Vaccine Advocacy Coalition, and Family Health International.
The site includes features such as a browsable database of scientific abstracts and full-text articles; an inventory of research activities on male circumcision; tools and guidelines for provider training and program scale-up; and evidence-based protocols and guidelines. It will be continually updated with emerging information on country progress in expanding access to safe male circumcision services, including lessons learned in implementation, say program officials.
References
- Tobian AA, Serwadda D, Quinn TC, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med 2009; 360:1,298-1,309.
- Bailey C, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomized controlled trial. Lancet 2007; 369:643-656.
- Gray H, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in young men in Rakai, Uganda: A randomized trial. Lancet 2007; 369:657-666.
- Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med 2005; 2:e298.
- Golden MR, Wasserheit JN. Prevention of viral sexually transmitted infections — foreskin at the forefront. N Engl J Med 2009; 360:1,349-1,351.
- Xu F, Markowitz LE, Sternberg MR, et al. Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: The National Health and Nutrition Examination Survey (NHANES), 1999-2004. Sex Transm Dis 2007; 34:479-484.
- Hallamore S, Yow M, Webb D, et al. Remnant foreskin contains fewer Langerhans' cells — implications for human immunodeficiency transmission in circumcised men. Presented at the 104th Annual Scientific Meeting of the American Urological Association. Chicago; April 2009.
- Krieger J, Mehta S, Bailey R, et al. Adult male circumcision: Effects on sexual function and penile coital injuries. Presented at the 104th Annual Scientific Meeting of the American Urological Association. Chicago; April 2009.
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