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      Male circumcision and penile cancer: a systematic review and meta-analysis

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          Abstract

          Objective

          We systematically reviewed the evidence of an association between male circumcision and penile cancer.

          Methods

          Databases were searched using keywords and text terms for the epidemiology of penile cancer. Random effects meta-analyses were used to calculate summary odds ratios (ORs) and 95% confidence intervals (CI).

          Results

          We identified eight papers which evaluated the association of circumcision with penile cancer, of which seven were case–control studies. There was a strong protective effect of childhood/adolescent circumcision on invasive penile cancer (OR = 0.33; 95% CI 0.13–0.83; 3 studies). In two studies, the protective effect of childhood/adolescent circumcision on invasive cancer no longer persisted when analyses were restricted to boys with no history of phimosis.

          In contrast, there was some evidence that circumcision in adulthood was associated with an increased risk of invasive penile cancer (summary OR = 2.71; 95% CI 0.93–7.94; 3 studies). There was little evidence for an association of penile intra-epithelial neoplasia and in situ penile cancer with circumcision performed at any age.

          Conclusions

          Men circumcised in childhood/adolescence are at substantially reduced risk of invasive penile cancer, and this effect could be mediated partly through an effect on phimosis. Expansion of circumcision services in sub-Saharan Africa as an HIV prevention strategy may additionally reduce penile cancer risk.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s10552-011-9785-9) contains supplementary material, which is available to authorized users.

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          Most cited references 31

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          Measuring inconsistency in meta-analyses.

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            Trends in cancer incidence in Kyadondo County, Uganda, 1960–1997

            Incidence rates of different cancers have been calculated for the population of Kyadondo County (Kampala, Uganda) for four time periods (1960–1966; 1967–1971; 1991–1994; 1995–1997), spanning 38 years in total. The period coincides with marked social and lifestyle changes and with the emergence of the AIDS epidemic. Most cancers have increased in incidence over time, the only exceptions being cancers of the bladder and penis. Apart from these, the most common cancers in the early years were cervix, oesophagus and liver; all three have remained common, with the first two showing quite marked increases in incidence, as have cancers of the breast and prostate. These changes have been overshadowed by the dramatic effects of the AIDS epidemic, with Kaposi's sarcoma emerging as the most common cancer in both sexes in the 1990s, and a large increase in incidence of squamous cell cancers of the conjunctiva. In the most recent period, there also seems to have been an increase in the incidence of non-Hodgkin lymphomas. So far, lung cancer remains rare. Cancer control in Uganda, as elsewhere in sub-Saharan Africa, faces a threefold challenge. With little improvement in the incidence of cancers associated with infection and poverty (liver, cervix, oesophagus), it must face the burden of AIDS-associated cancers, while coping with the emergence of cancers associated with Westernization of lifestyles (large bowel, breast and prostate). © 2000 Cancer Research Campaign
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              Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease.

              Few population-based case-control studies have assessed etiologic factors for penile cancer. Past infection with high-risk human papillomavirus (HPV) is a known risk factor for penile cancer; however, few previous studies have related the HPV DNA status of the tumor to potential demographic and behavioral risk factors for the disease or evaluated whether in situ and invasive penile cancer share risk factors. Little information is available on the role and timing of circumcision in the etiology of penile cancer. We conducted a population-based case-control study in western Washington state that included 137 men diagnosed with in situ (n = 75) or invasive (n = 62) penile cancer between January 1, 1979, and December 31, 1998, and 671 control men identified through random digit dialing. Cases and controls were interviewed in person and provided peripheral blood samples. Case and control blood samples were tested for antibodies to HPV16 and HSV-2, and tumor specimens from cases were tested for HPV DNA. Men not circumcised during childhood were at increased risk of invasive (OR = 2.3, 95% CI 1.3-4.1) but not in situ (OR = 1.1, 95% CI 0.6-1.8) penile cancer. Approximately 35% of men with penile cancer who had not been circumcised in childhood reported a history of phimosis compared to 7.6% of controls (OR = 7.4, 95% CI 3.7-15.0). Penile conditions such as tear, rash and injury were associated with increased risk of disease. Among men not circumcised in childhood, phimosis was strongly associated with development of invasive penile cancer (OR = 11.4, 95% CI 5.0-25.9). When we restricted our analysis to men who did not have phimosis, the risk of invasive penile cancer associated with not having been circumcised in childhood was not elevated (OR = 0.5, 95% CI 0.1-2.5). Cigarette smoking was associated with a 4.5-fold risk (95% CI 2.0-10.1) of invasive penile cancer. HPV DNA was detected in 79.8% of tumor specimens, and 69.1% of tumors were HPV16-positive. The proportion of HPV DNA-positive tumors did not vary by any risk factors evaluated. Many risk factors were common for both in situ and invasive disease. However, 3 factors that did not increase the risk for in situ cancer proved significant risk factors for invasive penile cancer: lack of circumcision during childhood, phimosis and cigarette smoking. The high percentage of HPV DNA-positive tumors in our study is consistent with a strong association between HPV infection and the development of penile cancer regardless of circumcision status. Circumcision in early childhood may help prevent penile cancer by eliminating phimosis, a significant risk factor for the disease. (c) 2005 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Natasha.larke@lshtm.ac.uk
                Journal
                Cancer Causes Control
                Cancer Causes & Control
                Springer Netherlands (Dordrecht )
                0957-5243
                1573-7225
                22 June 2011
                22 June 2011
                August 2011
                : 22
                : 8
                : 1097-1110
                Affiliations
                [1 ]MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT UK
                [2 ]Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT UK
                [3 ]Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT UK
                Article
                9785
                10.1007/s10552-011-9785-9
                3139859
                21695385
                © The Author(s) 2011
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media B.V. 2011

                Oncology & Radiotherapy

                papillomavirus infections, penile neoplasms, phimosis, male circumcision

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