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Male circumcision for the prevention of HSV-2 infection in men

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Circumcision of men, already known to decrease the incidence of HIV infection, has now been shown to prevent some cases of genital HSV-2 infection.

What’s known?

  • There is compelling evidence (three RCTs and many observational studies) that male circumcision reduces the risk of heterosexually acquired HIV infection in men by approximately 60%
  • Three randomized controlled trials have also shown that male circumcision provided by well trained health professionals in properly equipped settings is safe
  • Male circumcision provides only partial protection, and therefore should be only one element of a comprehensive HIV prevention policy

What’s new?

  • This study used data from 2 RCTs conducted in Rakai, Uganda, that enrolled a total of 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in trials of male circumcision for the prevention of HIV and other sexually transmitted infections
  • These studies involved physical examinations and interviews to ascertain sociodemographic characteristics and rates of sexual practices at baseline and at 6, 12, and 24 months
  • Of the 3393 (61.3%) HSV-2–seronegative subjects at the enrollment, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group)
  • HSV-2 testing was performed with the use of an enzyme-linked immunosorbent assay (ELISA) (Kalon Biological). (An optical-density index value of 1.5 or more was reported as positive) and all seroconversions were confirmed by Western blot (Euroimmun)
  • Results showed that at 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44)
  • Authors 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.
Research summary
Author(s): 

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.

Full title: 

Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis.

Publication details: 

N Engl J Med 2009 360: 1298-1309

Abstract: 

Background Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men.

Methods We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2–seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months.

Results At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44).

Conclusions 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. (ClinicalTrials.gov numbers, NCT00425984 [ClinicalTrials.gov] and NCT00124878 [ClinicalTrials.gov] .)

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