Male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition: a meta-analysis Sanjeev C. Sharma* , Nicholas Raison † , Shamim Khan † , Majid Shabbir ‡ , Prokar Dasgupta † and Kamran Ahmed † *GKT School of Medical Education, † Division of Transplantation Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King’s College London, London, UK, and ‡ Department of Urology, Guy’s and St Thomas’ NHS Trust, London, UK 7 BJUI Systematic Review Quality Score (based on AMSTAR) We aimed to assess male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition in heterosexual and homosexual men using all available data. A systematic literature review was conducted searching for studies that assessed male circumcision as a method to prevent HIV acquisition in homosexual and/or heterosexual men. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched in March 2017. A random effects model was used to calculate a pooled risk ratio (RR) and its associated 95% confidence interval (CI). In total, 49 studies were included in this meta-analysis. The overall pooled RR for both homosexual and heterosexual men was 0.58 (95% CI 0.48– 0.70), suggesting that circumcision was associated with a reduction in HIV risk. Circumcision was found to be protective for both homosexual and heterosexual men (RR: 0.80, 95% CI 0.69–0.92 and 0.28, 95% CI 0.14–0.59, respectively). Heterosexual men had a greater RR reduction (72% compared with 20% for homosexual men). There was significant heterogeneity among the studies (v 2 = 1378.34, df = 48; I 2 = 97%). This meta-analysis shows that male circumcision was effective in reducing HIV risk for both heterosexual and homosexual men. Keywords circumcision, human immunodeficiency virus, prevention, voluntary medical male circumcision Introduction The WHO and United Nations estimate that ~30% of men are circumcised globally, predominantly in Asia, the Middle East and North Africa [1]. Reasons for circumcision include religious/traditional ritual, resolving infection, foreskin injury or abnormality. A relationship between male circumcision and prevention of sexually transmitted infections (STIs) was suggested as early as the 1850s [2]; however, it was not until the 1980s that circumcision was considered as a means of HIV prevention [3]. Since then, a great amount of data have been published, mostly supportive of this protective effect. Various theories have been proposed to explain the mechanism by which circumcision could reduce HIV. Circumcision may act indirectly by reducing the risk of STIs, and the data suggest that these infections increase the risk of HIV acquisition [4]. The impact of circumcision on STI risk was investigated as a secondary outcome of the present review. Circumcision could also have a more direct effect because the under-surface of the foreskin contains Langerhans’ cells and CD4 + T lymphocytes, which are target cells of the HIV virus [5]; foreskin removal therefore removes HIV targets. It has also been suggested that small tears occurring in the fragile foreskin are used as entry points for the virus [6]. The foreskin may aid HIV infection by trapping contaminated fluids or simply by providing a warm, moist environment for infections to thrive [6,7]. In the present meta-analysis, we aimed to assess a broad research base by including randomized controlled trials (RCTs), cohort, case–control and cross-sectional studies. Previous reports have either not separated studies into homosexual and heterosexual cohorts or have only investigated one sexuality. We aimed to explore both heterosexual and homosexual HIV transmission, together and © 2017 The Authors BJU International © 2017 BJU International | doi:10.1111/bju.14102 BJU Int 2018; 121: 515–526 Published by John Wiley & Sons Ltd. www.bjui.org wileyonlinelibrary.com Systematic Review and Meta-Analysis