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

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.

Male Circumcision

“…68 An additional cohort study with fair evidence found that circumcised men were significantly less likely to have active syphilis at the point of study recruitment; when the men were followed up prospectively for 2 years, a protective effect was also observed but was nonsignificant. 69 Good evidence from a large RCT reported no reduction or trend toward reduction for male circumcision and the incidence of syphilis 71 ; however, the extent to which protection might be afforded, and among which specific populations, is difficult to determine. One meta-analysis with good evidence found some protective effect of circumcision against HSV-2 of borderline statistical significance.…”

“…73 In the Uganda study, the risk of HSV-2 infection (adjusted for other factors) was 28% lower in circumcised men. 71 There is fair evidence from 1 study that male circumcision protects female partners against HSV-2 infection. 33 Two studies with fair evidence found that there is no effect of circumcision on the risk of HSV-2 acquisition.…”

“…102 In the Uganda study, the risk of oncogenic HPV infection (adjusted for other factors) was 35% lower in circumcised men. 71 There is also good evidence that male circumcision reduces the risk of maleto-female transmission of high-risk HPV from HIV-uninfected men. In the Uganda randomized controlled trial, the prevalence of high-risk HPV infection was 28% lower in female partners of circumcised HIV-uninfected men, while the incidence was 23% lower.…”

Unresolved questions concerning human papillomavirus infection and transmission: a modelling perspective

“…Recent randomised control trials have reported beneficial effects of circumcision on HPV acquisition and clearance in males in Africa. 82,84,86 However, Van Howe has suggested that these results can be completely explained by sampling bias 87 and has highlighted inadequacies in the methods used for sampling the penis in another study. 80,81 The evidence for whether condoms are a highly effective barrier against transmission of HPV between partners is conflicting.…”

“…A variety of studies have been conducted to investigate the effectiveness of circumcision in the prevention of HPV infection [78][79][80][81][82][83][84][85][86][87][88] and the interpretation of the findings from these is currently under debate. Recent randomised control trials have reported beneficial effects of circumcision on HPV acquisition and clearance in males in Africa.…”