Association between male circumcision and human papillomavirus infection in males and females: a systematic review, meta-analysis, and meta-regression
Authors: Shapiro Samantha B. , Laurie Cassandra , El-Zein Mariam , Franco Eduardo L. 
Published: August 2022

ABSTRACTBackgroundHuman papillomavirus (HPV) infection is a necessary cause of cervical cancer and is associated with anal, penile, vaginal, and vulvar cancers. Previous studies have suggested a protective effect of male circumcision (MC) on HPV infections in males, and that this protection may be conferred to their female sexual partners. We synthesized the available evidence on the association between MC and HPV infections in males and females.MethodsWe performed a systematic review and meta-analysis of the effect of MC on the prevalence, incidence, and clearance of genital HPV infections in heterosexual males and their female sexual partners. We searched multiple databases for studies that assessed MC status and tested for the presence of genital HPV DNA. We used random-effects meta-analysis models to estimate summary measures of effect and 95% confidence intervals (CI) for the prevalence, incidence, and clearance of HPV infections in males and females. We assessed effect modification for prevalence in males using random-effects meta-regression.FindingsWe included 32 publications encompassing 25 unique study populations. MC was associated with decreased odds of prevalent HPV infections (odds ratio 0·45, CI 0·34–0·61), a reduced rate of incident HPV infections (incidence rate ratio 0·69, CI 0·57–0·83), and an increased risk of clearing HPV infections (risk ratio 1·44, CI 1·28–1·61) at the glans penis. Effect modification by sampling site was observed for HPV prevalence in males, with greater protection conferred by MC at the glans than the shaft (OR 0·68, 95% CI 0·48–0·98). Females with circumcised sexual partners were at reduced risk for all outcomes.InterpretationMC protects against various HPV infection outcomes, especially at the glans, and may be a viable prophylactic strategy in regions with a high burden of HPV-associated disease where the HPV vaccine is not commercially available. That the protective effect of MC on HPV infection prevalence varies by penile site has important implications for epidemiologic studies of HPV transmission.FundingFunded by grant FDN-143347 from the Canadian Institutes of Health Research.RESEARCH IN CONTEXTEvidence before this studyPrevious meta-analyses published in 2011, 2012, and 2017 have assessed the impact of MC on genital HPV infections in males, while systematic reviews published in 2017 and 2019 have described the impact of MC on women’s sexual health outcomes. All meta-analyses of males found a protective effect of MC on HPV prevalence, with inconsistent evidence for the association between MC and HPV incidence and clearance. Systematic reviews in females found a protective effect of MC on HPV prevalence.Added value of this studyWe identified an additional 12 publications (including one randomized controlled trial) that were not included in the most recently published systematic review and meta-analysis. We found that in males, MC conferred protection against prevalent HPV infections at the glans and shaft of the penis, protected against the acquisition of HPV infections at the glans, and resulted in increased clearance of HPV infections at the glans and shaft. We also found that MC protected females against various HPV infection outcomes. We considered anatomical site in all analyses and explored effect modification using a meta-regression approach. Our meta-analysis also examined the impact of MC on various HPV infection outcomes in females. To our knowledge, the latter two types of analyses had not been done before.Implications of all the available evidenceCountries with a high burden of HPV-associated diseases, or where the HPV vaccine is not commercially available, may wish to consider male circumcision as a preventive strategy. Both males and their female sexual partners may benefit from MC for protection from HPV infections.