A new study by researchers in the US found that male circumcision cut the risk of genital herpes and human papillomavirus (HPV) infection, but not syphilis.

The study, which is published in the 26 March issue of the New England Journal of Medicine, NEJM, was the work of scientists at the Rakai Health Sciences Program in Uganda and researchers at the Johns Hopkins University Bloomberg School of Public Health in Baltimore, Makerere University in Kampala, Uganda, and the Division of Intramural Research at the National Institute of Allergy and Infectious Disease (NIAID).

The researchers studied data from two clinical trials in Rakai that showed male circumcision reduced the incidence of HIV infection. One trial was funded by NIAID and the other by the Bill & Melinda Gates Foundation.

NIAID Director Dr Anthony S Fauci told the press that:

“Medically supervised adult male circumcision is a scientifically proven method for reducing a man’s risk of acquiring HIV infection through heterosexual intercourse.”

“This new research provides compelling evidence that circumcision can provide some protection against genital herpes and human papillomavirus infections as well.”

For this study, the researchers assessed the effectiveness of male circumcision in preventing infection by the herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) and syphilis in HIV-negative adolescent boys and men (aged from 15 to 49). HSV-2 causes of genital herpes, and HPV can cause cancer and genital warts.

3,393 (61.3 per cent) of the 5,534 participants enrolled in the two trials tested negative for HSV-2, and of these 1,684 had been randomly assigned to undergo immediate circumcision performed by trained medical professionals, and 1,709 to have it 24 months later (the controls).

At the start of the study (baseline), at 6, 12 and 24 months, all participants were tested for HSV-2, HIV and syphilis and underwent physical exams and interviews. A subgroup of 697 participants was also tested for HPV at baseline and 24 months (352 in the circumcision group and 345 in the control group).

The results showed that:

  • At 24 months, the cumulative probability of infection by HSV-2 was 7.8 per cent in the circumcision group and 10.3 per cent in the control group.
  • Overall, medically supervised circumcision reduced the men’s risk of HSV-2 infection by 28 per cent (adjusted hazard ratio in the circumcision group, 0.72; with 95 per cent confidence interval [CI] ranging from 0.56 to 0.92; P=0.008).
  • The prevalence of high-risk HPV genotypes was 18.0 per cent in the circumcision group and 27.9 per cent in the control group, with a risk reduction of 35 per cent in the circumcision group (adjusted risk ratio, 0.65; 95 per cent CI, 0.46 to 0.90; P=0.009).
  • However, there was no significant difference between the two study groups in the incidence of syphilis (adjusted hazard ratio, 1.10; 95 per cent CI, 0.75 to 1.65; P=0.44).

The researchers concluded that:

“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.”

Co-author Dr Thomas C. Quinn, who heads the the International HIV/STD Section in NIAID’s Laboratory of Immunoregulation, said:

“The cumulative scientific evidence supporting the public health value of medically supervised male circumcision is now overwhelming.”

“This new research confirms the substantial health benefits of male circumcision, including reduced acquisition of HIV, genital herpes, HPV and genital ulcer disease.”

Co-principal investigator Dr David Serwadda, who is dean of Makerere University’s School of Public Health, added:

“These findings have significant public health implications for the control of HIV, genital herpes and HPV in areas of high prevalence, such as Africa, and further suggest that efforts to scale-up male circumcision could have tremendous benefit.”

Johns Hopkins Professor Ronald H Gray, co-principal investigator of the study said:

“The next focus of our research will be to analyze additional data collected in the Rakai trials to assess the degree to which male circumcision may reduce transmission of HPV to female sexual partners.”

“This would be of substantial significance because HPV causes cervical cancer,” he added.

The researchers said they don’t know why circumcision may reduce the risk of HSV-2 and HPV infection but not syphilis.

The foreskin helps the HSV-2 and HPV viruses to get into the epithelial cells in the surface skin of the penis where they multiply. Circumcision removes the foreskin and perhaps reduces risk of epithelial infection.

Another reason for the odd result with syphilis could be the low statistical power of the analysis (presumably because of low numbers of syphilis cases) said the researchers, making it difficult to draw a firm conclusion about syphilis and circumcision.

“Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis.”
Tobian, Aaron A.R., Serwadda, David, Quinn, Thomas C., Kigozi, Godfrey, Gravitt, Patti E., Laeyendecker, Oliver, Charvat, Blake, Ssempijja, Victor, Riedesel, Melissa, Oliver, Amy E., Nowak, Rebecca G., Moulton, Lawrence H., Chen, Michael Z., Reynolds, Steven J., Wawer, Maria J., Gray, Ronald H.
N Engl J Med March 26, 2009, Volume 360:1298-1309, Number 13.

Sources: NIH/National Institute of Allergy and Infectious Diseases, NEJM.

Written by: Catharine Paddock, PhD