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      Does Male Circumcision Protect against Sexually Transmitted Infections? Arguments and Meta-Analyses to the Contrary Fail to Withstand Scrutiny

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          Abstract

          We critically evaluate a recent article by Van Howe involving 12 meta-analyses that concludes, contrary to current evidence, that male circumcision increases the risk of various common sexually transmitted infections (STIs). Our detailed scrutiny reveals that these meta-analyses (1) failed to include results of all relevant studies, especially data from randomized controlled trials, (2) introduced bias through use of inappropriate control groups, (3) altered original data, in the case of human papillomavirus (HPV), by questionable adjustments for “sampling bias,” (4) failed to control for confounders through use of crude odds ratios, and (5) used unnecessarily complicated methods without adequate explanation, so impeding replication by others. Interventions that can reduce the prevalence of STIs are important to international health. Of major concern is the global epidemic of oncogenic types of HPV that contribute to the burden of genital cancers. Meta-analyses, when well conducted, can better inform public health policy and medical practice, but when seriously flawed can have detrimental consequences. Our critical evaluation leads us to reject the findings and conclusions of Van Howe on multiple grounds. Our timely analysis thus reaffirms the medical evidence supporting male circumcision as a desirable intervention for STI prevention.

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          Male circumcision for the prevention of HSV-2 and HPV infections and syphilis.

          Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2-seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months. At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44). In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure. (ClinicalTrials.gov numbers, NCT00425984 and NCT00124878.) 2009 Massachusetts Medical Society
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            Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners.

            It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.
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              Testing and adjusting for publication bias

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                Author and article information

                Journal
                ISRN Urol
                ISRN Urol
                ISRN.UROLOGY
                ISRN Urology
                Hindawi Publishing Corporation
                2090-5807
                2090-5815
                2014
                13 May 2014
                : 2014
                : 684706
                Affiliations
                1School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
                2Department of Global Health, Academic Medical Centre and Amsterdam Institute for Global Health and Development, University of Amsterdam, 1100DE, Amsterdam, The Netherlands
                3Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK
                4Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
                5Section of Urology University of Washington School of Medicine and VA Puget Sound Health Care System, Seattle, WA 98108, USA
                6Division of Infectious Diseases and Program in Global Health, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA
                Author notes

                Academic Editors: P. Crispen, J. S. Elder, G. Haidl, J. H. Ku, and E. Yilmaz

                Article
                10.1155/2014/684706
                4040210
                24944836
                4dae529b-5899-4253-8ba0-fa5e02bce189
                Copyright © 2014 Brian J. Morris et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 October 2013
                : 4 February 2014
                Categories
                Review Article

                Urology
                Urology

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