Is circumcision an answer for HIV prevention in men who have sex with men?

The meta-analysis1Yuan T Fitzpatrick T Ko NY et al.Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data.Lancet Glob Health. 2019; 7: e436-e447Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar and accompanying Comment2Pintye J Baeten JM Benefits of male circumcision for MSM: evidence for action.Lancet Glob Health. 2019; 7: e388-e389Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar addressing circumcision and HIV infection in men who have sex with men (MSM) might reflect a confirmation bias. As a consultant at the US Centers for Disease Control and Prevention's 2007 consultation on public health issues regarding male circumcision in the USA,3Smith DK Taylor A Kilmarx PH et al.Male circumcision in the United States for the prevention of HIV infection and other adverse health outcomes: report from a CDC consultation.Public Health Rep. 2010; 125: 72-82Crossref PubMed Google Scholar I noted a palpable urgency among those invited—nearly all of whom were avowed circumcision advocates—to uncover or generate data proving that circumcision protects MSM from HIV infection. Now, 12 years later, circumcision advocates will be celebrating the accomplishment of this mission. Is their celebration justified? The aforementioned meta-analysis1Yuan T Fitzpatrick T Ko NY et al.Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data.Lancet Glob Health. 2019; 7: e436-e447Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar consisted of two large observational studies with consistent negative findings (odds ratios [ORs] 1·05, 95% CI 1·00–1·094Mor Z Kent CK Kohn RP Klausner JD Declining rates in male circumcision amidst increasing evidence of its public health benefit.PLoS One. 2007; 2: e861Crossref PubMed Scopus (42) Google Scholar and 1·00, 0·91–1·11)5Jozkowski K Rosenberger JG Schick V Herbenick D Novak DS Reece M Relations between circumcision status, sexually transmitted infection history, and HIV serostatus among a national sample of men who have sex with men in the United States.AIDS Patient Care STDS. 2010; 24: 465-470Crossref PubMed Scopus (17) Google Scholar and 43 smaller studies. As observational studies often include an assortment of patient populations and investigational methods, any meta-analysis of these studies must account for any significant between-study heterogeneity; otherwise, the results of the analysis are suspect.6Patsopoulos NA Evangelou E Ioannidis JP Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation.Int J Epidemiol. 2008; 37: 1148-1157Crossref PubMed Scopus (580) Google Scholar In this meta-analysis,1Yuan T Fitzpatrick T Ko NY et al.Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data.Lancet Glob Health. 2019; 7: e436-e447Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar removal of three outlier studies7Lane T Raymond HF Dladla S et al.High HIV prevalence among men who have sex with men in Soweto, South Africa: results from the Soweto men's study.AIDS Behav. 2011; 15: 626-634Crossref PubMed Scopus (169) Google Scholar, 8Yunihastuti E, Phanuphak N, Somia A, et al. Safer sexual practice among known HIV-positive compared to HIV-negative/unknown status men who have sex with men in Bangkok, Bali and Jakarta. XIX International AIDS Conference; Washington, DC, USA; July 22–27, 2012. Abstract THPE219.Google Scholar, 9Schneider JA Michaels S Gandham SR et al.A protective effect of circumcision among receptive male sex partners of Indian men who have sex with men.AIDS Behav. 2012; 16: 350-359Crossref PubMed Scopus (16) Google Scholar (1·05% of all participants) would reduce heterogeneity from high (I2=77%) to modest (I2=49·4%). In doing so, the random-effects summary OR for HIV infection would shift from 0·77 (0·67–0·89) to 0·90 (0·81–1·00), which is not statistically significant. Removal of an additional four outliers10Buchbinder SP Vittinghoff E Heagerty PJ et al.Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States.J Acquir Immune Defic Syndr. 2005; 39: 82-89Crossref PubMed Scopus (187) Google Scholar, 11Xu JJ Tang WM Zou HC et al.High HIV incidence epidemic among men who have sex with men in China: results from a multi-site cross-sectional study.Infect Dis Poverty. 2016; 5: 82Crossref PubMed Scopus (36) Google Scholar, 12Sanchez J Lama JR Peinado J et al.High HIV and ulcerative sexually transmitted infection incidence estimates among men who have sex with men in Peru: awaiting for an effective preventive intervention.J Acquir Immune Defic Syndr. 2009; 51: S47-S51Crossref PubMed Scopus (58) Google Scholar, 13Golden MR, Brewer DD, Wood RW, Holmes K, Handsfield H. Association of methamphetamine use with HIV among MSM tested for HIV in an STD clinic. 15th International Society for Sexually Transmitted Diseases Research; Ottawa, ON, Canada; July 27–30, 2003. Abstract 0300.Google Scholar (another 8·94% of participants) would reduce heterogeneity to the low range (I2=22·4%), shifting the summary OR to 0·96 (0·89–1·04). A meta-analysis with clear evidence of publication bias, such as this one, can be adjusted using the trim and fill approach.14Duval S Tweedie R Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.Biometrics. 2000; 56: 455-463Crossref PubMed Scopus (7714) Google Scholar The fill approach indicated seven potentially missing studies, which, when added, shifted the random-effects summary OR to 0·87 (0·77–0·99). Policy positions should be based on a firm scientific foundation. The Oxford Centre for Evidence-based Medicine attributes a 3a quality rating to meta-analyses of case-control studies if there is homogeneity. However, this meta-analysis1Yuan T Fitzpatrick T Ko NY et al.Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data.Lancet Glob Health. 2019; 7: e436-e447Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar did not have homogeneity. Going from the two large studies,4Mor Z Kent CK Kohn RP Klausner JD Declining rates in male circumcision amidst increasing evidence of its public health benefit.PLoS One. 2007; 2: e861Crossref PubMed Scopus (42) Google Scholar, 5Jozkowski K Rosenberger JG Schick V Herbenick D Novak DS Reece M Relations between circumcision status, sexually transmitted infection history, and HIV serostatus among a national sample of men who have sex with men in the United States.AIDS Patient Care STDS. 2010; 24: 465-470Crossref PubMed Scopus (17) Google Scholar which accounted for 43·6% of the participants and had consistent results, to 45 studies that had significant between-study heterogeneity and publication bias has only added noise to the discussion of this topic. I declare no competing interests. Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global dataWe found evidence that circumcision is likely to protect MSM from HIV infection, particularly in countries of low and middle income. Circumcision might also protect MSM from HSV and penile HPV infection. MSM should be included in campaigns promoting circumcision among men in countries of low and middle income. In view of the substantial proportion of MSM in countries of low and middle income who also have sex with women, well designed longitudinal studies differentiating MSM only and bisexual men are needed to clarify the effect of circumcision on male-to-male transmission of HIV and other STIs. Full-Text PDF Open AccessIs circumcision an answer for HIV prevention in men who have sex with men? – Authors' replyWe thank Robert Van Howe for his comments on our meta-analysis.1 Despite the large sample sizes of the observational studies by Mor and colleagues2 and Jozkowski and colleagues3 mentioned in Van Howe's letter, those studies each had a high risk of bias (with crude odds ratios [ORs], single-centre setting, and self-reported HIV and circumcision), meeting only three2 and one3 of the seven Newcastle-Ottawa Scale criteria. In fact, restricting our analysis to the 14 studies that adjusted for confounders led to an increase in the protective association between circumcision and HIV (OR 0·64, 95% CI 0·45–0·93). Full-Text PDF Open Access

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