Association between male circumcision and human papillomavirus infection in males and females: a systematic review, meta-analysis, and meta-regression

Background: Previous studies have suggested a protective effect of male circumcision on human papillomavirus (HPV) infections in males, and that this protection may be conferred to their female sexual partners.

Objectives: To synthesize the available evidence on the association between male circumcision and HPV infections in males and females.

Data sources: We searched MEDLINE, Embase, Scopus, Cochrane, LILACS, and ProQuest Dissertations & Theses Global for records published up to 22 June 2022.

Study eligibility: We considered observational and experimental studies that assessed male circumcision status and HPV prevalence, incidence, or clearance in males or females for inclusion.

Participants: Males and their female sexual partners who were tested for genital HPV infection.

Interventions: Male circumcision compared with no circumcision.

The risk-of-bias assessment: The Newcastle-Ottawa scale was used for observational studies, and the Cochrane risk-of-bias tool was used for randomized trials.

Data synthesis: We estimated summary measures of effect and 95% CIs for the prevalence, incidence, and clearance of HPV infections in males and females using random-effects meta-analysis. We assessed the effect modification of circumcision on HPV prevalence by the penile site in males using random-effects meta-regression.

Results: Across 32 studies, male circumcision was associated with decreased odds of prevalent HPV infections (odds ratio, 0.45; 95% CI, 0.34-0.61), a reduced incidence rate of HPV infections (incidence rate ratio, 0.69; 95% CI, 0.57-0.83), and an increased risk of clearing HPV infections (risk ratio, 1.44; 95% CI, 1.28-1.61) at the glans penis among male subjects. Circumcision conferred greater protection against infection at the glans than the shaft (odds ratio, 0.68; 95% CI, 0.48-0.98). Females with circumcised partners were protected from all outcomes.

Conclusions: Male circumcision may protect against various HPV infection outcomes, suggesting its prophylactic potential. Understanding the site-specific effects of circumcision on HPV infection prevalence has important implications for studies of HPV transmission.