Circumcision may reduce HIV, HSV-2, HPV

Circumcision May Reduce Incidence of HIV, HSV-2, HPV Infection CME
News Author: Laurie Barclay, MDCME Author: Charles Vega, MD, FAAFP
Authors and Disclosures
Laurie Barclay, MDDisclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Charles Vega, MD, FAAFPDisclosure: Charles Vega, MD, FAAFP, has disclosed an advisor/consultant relationship to Novartis, Inc.
Brande Nicole MartinDisclosure: Brande Nicole Martin has disclosed no relevant financial information.

March 25, 2009 — Male circumcision significantly reduced the incidence of HIV and herpes simplex virus type 2 (HSV-2) infection and the prevalence of human papillomavirus (HPV) infection, suggesting potential public health benefits, according to the results of a randomized controlled trial reported in the March 26 issue of the New England Journal of Medicine.
"Male circumcision significantly reduced the incidence of...HIV infection among men in three clinical trials," write Aaron A.R. Tobian, MD, PhD, from Bloomberg School of Public Health, Johns Hopkins University in Baltimore, Maryland, and colleagues. "We assessed the efficacy of male circumcision for the prevention of...HSV-2 and...HPV infections and syphilis in HIV-negative adolescent boys and men." Two trials of male circumcision to prevent HIV and other sexually transmitted infections in a rural Ugandan population enrolled a total of 5534 HIV-negative, uncircumcised male subjects aged 15 to 49 years. Of 3393 subjects (61.3%) who were HSV-2 seronegative at enrollment, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). Subjects were tested for HSV-2 and HIV infection and syphilis and underwent physical examinations and interviews at baseline and at 6, 12, and 24 months. A subgroup of subjects was also evaluated for HPV infection at baseline and at 24 months. The cumulative probability of HSV-2 seroconversion by 24 months was 7.8% in the intervention group vs 10.3% in the control group (adjusted hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.56 - 0.92; P = .008). High-risk HPV genotypes were present at 24 months in 18.0% of the intervention group vs 27.9% of the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 - 0.90; P = .009). The incidence of syphilis was not significantly different between groups (adjusted HR, 1.10; 95% CI, 0.75 - 1.65; P = .44). "In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure," the study authors write. "These 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. However, it must be emphasized that protection was only partial, and it is critical to promote the practice of safe sex." Limitations of this study include evaluation of the use of circumcision to prevent HPV infection only in a subgroup of subjects observed both at enrollment and at 24 months.
"Male circumcision has now been shown to decrease the rates of HIV, HSV-2, and HPV infections in men and of trichomoniasis and bacterial vaginosis in their female partners," the study authors conclude. "Circumcision also reduces symptomatic ulceration in HIV-negative men and women and HIV-positive men. Thus, male circumcision reduces the risk of several sexually transmitted infections in both sexes, and these benefits should guide public health policies for neonatal, adolescent, and adult male circumcision programs." In an accompanying editorial, Matthew R. Golden, MD, MPH, and Judith N. Wasserheit, MD, MPH, from the University of Washington, Public Health–Seattle, note that this study contributes strong evidence that circumcision offers an important prevention opportunity and should be widely available. "Professional organizations have a leadership role to play in ensuring that medical providers actively educate all parents or guardians of newborn sons about the benefits and risks of circumcision," Drs. Golden and Wasserheit write. "The American Academy of Pediatrics, which previously concluded that evidence was insufficient to recommend routine neonatal circumcision, is reviewing its position in collaboration with other professional organizations. This process should optimally lead to a multidisciplinary consensus statement involving providers such as obstetricians, midwives, pediatricians, urologists, and family doctors and to the development and dissemination of educational materials for medical professionals and families." The National Institutes of Health, the Bill and Melinda Gates Foundation, the Fogarty International Center, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases supported this study. Coauthor Patti E. Gravitt, PhD, has received research funding from Roche Molecular Diagnostics, maker of the HPV genotyping test used in this study. The other study authors have disclosed no relevant financial relationships. Dr. Golden has received lecture fees from Pfizer and drugs donated by Pfizer and Lupon Pharmaceuticals for research funded by the National Institutes of Health. Dr. Wasserheit has received research support from the Bill and Melinda Gates Foundation.
N Engl J Med. 2009;360:1298-1309.
Clinical Context
Circumcision has been demonstrated to reduce the risk for sexually transmitted infection, particularly with HIV, in previous research, and the current article describes potential mechanisms by which circumcision may be protective. In uncircumcised men, the retraction of the foreskin during intercourse exposes the inner preputial mucosa to potentially infectious fluids, and this area might be particularly prone to microtears, especially at the frenulum. The moist, humid environment of the subpreputial cavity may particularly promote infection. Moreover, this area is lightly keratinized, and this may facilitate viral access to underlying epithelial cells. Conversely, the scar and dense keratin after circumcision can create the opposite effect. The current study examines whether circumcision can reduce the rate of infection with HSV-2, HPV, and syphilis.
Study Highlights
The current study reports on 2 parallel trials performed in Uganda. Both trials enrolled uncircumcised male subjects between the ages of 15 and 49 years who had negative testing results for HIV. The current analysis focuses on participants who were HSV-2 seronegative at enrollment. Participants were randomly assigned to undergo immediate circumcision or circumcision at 24 months (control group). The main outcome of the study was the rate of sexually transmitted infection. Participants underwent testing at baseline and at 6, 12, and 24 months for infection with HSV-2 and syphilis. In addition, a subgroup of men was tested for infection with HPV at baseline and at 24 months. 1684 men were assigned to immediate circumcision, and 1709 comprised the control group. Demographic and sexual practice data were similar in comparing the 2 groups. Rates of condom use were higher in the circumcision vs the control group at 6 months, but these rates were similar thereafter. Although the number of sexual partners was similar in comparing randomized groups, more participants in the circumcision group reported nonmarital sexual relationships. The cumulative probability of HSV-2 infection was lower in the circumcised group (7.8%) vs the control group (10.3%) at 24 months. This yielded a significant adjusted HR of 0.72 for HSV-2 infection in the circumcised cohort. Circumcision was not protective against syphilis infection. At baseline, the prevalence of high-risk HPV genotypes was 38.1% in the circumcision group and 37.1% in the control group. At 24 months, the respective rates of HPV infection were 18% and 27.9%. The adjusted risk ratio of 0.65 in the circumcision group for this outcome was statistically significant.
Circumcision was also protective against infection with multiple high-risk HPV types as well as non–high-risk HPV types.