Male Circumcision Decreases Acquisition and Increases Clearance of High‐Risk Human Papillomavirus in HIV‐Negative Men: A Randomized Trial in Rakai, Uganda

Abstract

Uncircumcised HIV-negative men aged 15-49 years were randomized to immediate circumcision (n=441) or delayed circumcision (n=399). HPV was detected by Roche HPV Linear Array at enrollment, 6, 12 and 24 months. Incident HR-HPV was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RR) and 95% confidence intervals (95%CI) of HR-HPV acquisition were estimated by Poisson multiple regression Enrollment characteristics were comparable between groups. HR-HPV incidence was 19.7/100 py in the intervention (70/355.8 py) and 29.4/100 py (125/424.8 py) in the control arm (RR=0.67, 95%CI 0.51-0.89, p = 0.006.) The incidence of multiple HR-HPV infections was 6.7/100 py in the intervention and 14.8/100 py in control arm (RR = 0.45, 95%CI 0.28-0.73), but there was no significant effect on single infections (RR=0.89, 95%CI 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of pre-existing HR-HPV infections was 215.8/100py (205/95 py) in intervention and 159.1/100py (255/160.25 py) in control arm men (adjRR=1.39, 95%CI 1.17-1.64). Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men. The trial was registered with ClinicalTrials.gov numbers NCT00425984

Cervical Cancer Screening and Prevention for HIV-Infected Women in the Developing World

“…Male circumcision (MC) has been shown to reduce by reduce the risk of sexual HIV transmission from female to male by 60% (http://www.who.int/hiv/topics/malecircumcision/en/index.html) in randomized clinical trials. MC was also associated with a lower incidence of multiple high-risk HPV types and increased clearance of HR-HPVs as compared to controls (14.8% vs 22.3%, respectively) in Uganda (Gray et al 2010); however, MC was not associated with decreased incidence or increased clearance of HR-HPV in the female partners of circumcised men 24 months after the procedure, as compared to partners of men in the control group (Tobian et al 2011) However, MC has long been associated with reduced risk of cervical cancer in the wives of circumcised men; therefore further study is warranted.…”

CUA guideline on the care of the normal foreskin and neonatal circumcision in Canadian infants

“…Significantly, the prevalence differences between the 2 groups were not significant for HPV type 16 but were for HPV type 18. Six secondary trials analyzed HIV positive and negative men enrolled in the Ugandan HIV trial with regards to HPV prevalence, acquisition/incidence, clearance and viral load [89][90][91][92][93][94]. The first trial investigated the prevalence of HPV in a subgroup of participants and only included samples from the glans and coronal sulcus, a factor for possible bias due to differential infection sites in circumcised males [89,95].…”

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.…”