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Male circumcision and HPV transmission to female partners - Editorial
  The Lancet, Early Online Publication, 7 January 2011
Anna R Giuliano aEmail Address, Alan G Nyitray a, Ginesa Albero b c a Department of Cancer Epidemiology and Genetics, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA b IDIBELL, Institut Catala d'Oncologia-Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain c CIBER en Epidemiologia y Salud Publica, Barcelona, Spain
Male circumcision has been done for many years as a religious tradition, and since the 19th century has been thought to confer protection against sexually transmitted infections and diseases such as cervical cancer. In 1901, Braithwaite1 commented on the low incidence of cervical cancer in Jewish women-women who were married to circumcised men. Boyd and Doll later noted that cervical cancer is rare in communities in which men are circumcised.2 With the recognition that human papillomavirus (HPV) is causative in the development of cervical cancer, and with advances in methodology for the detection of HPV, further studies have supported these early observations that circumcision protects against HPV infection and cervical cancer in female partners.3-5
Bosch and colleagues noted that most published studies found an inverse association between male circumcision and penile HPV infection.6 Although many observational studies found a protective role for circumcision, definitive evidence was not obtained until randomised trials of adult male circumcision were completed. Data from these trials showed that adult male circumcision reduces the prevalence and incidence, and increases clearance, of most genital high-risk HPV infections in men.4, 5, 7 Furthermore, in a case-control study of cervical cancer in which the male partner was also interviewed, Castellsague and colleagues found that male circumcision was associated with a reduced risk of both cervical HPV infection and cervical cancer in women whose partners were circumcised.3
In The Lancet, Maria Wawer and colleagues' randomised trial8 now shows that circumcision reduces incidence and prevalence of high-risk HPV in female partners of circumcised men. In more than 1200 heterosexual couples, adult male circumcision significantly reduced the prevalence and incidence of HPV in women and increased clearance of infection. For example, prevalence of high-risk HPV in women was 27·8% in the intervention group and 38·7% in the control group (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). These data, from the most rigorous of study designs, support original observations for a preventive role of male circumcision in cervical cancer. In view of the complexity of such trials, this study will probably be the only one to provide direct evidence for male circumcision in the prevention of female HPV infections and, thus, in cervical cancer.
However, it is important to note three caveats. First, the reduction in high-risk HPV infection in women was limited to about 25%, Second, a clinical endpoint such as high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2/3) was not assessed. Third, clearance of HPV-16 was lower in the intervention group than in the control group. Although persistent high-risk HPV infections cause precancerous and cancerous lesions of the cervix, not all progress to these lesions. Therefore an estimate of cervical disease protection conferred by adult male circumcision remains unavailable. Furthermore, more than a third of women in both study groups already had high-risk HPV at baseline, and the effects of male circumcision provided before sexual debut cannot be estimated.
The prevalence of circumcision varies widely in both developing and developed countries, and seems to differ by birth cohort and socioeconomic status in developed countries such as the USA.9, 10 In the USA, scarcity of physicians' support and insurance coverage for the procedure seems to have negatively influenced rates of circumcision.11 In view of the increased evidence from randomised trials that male circumcision reduces risk of some sexually transmitted viral infections in men and in female partners,12 medical and public health organisations should take a firmer stand on recommendations for male circumcision. As with all prevention approaches, these recommendations should be consistent with the available evidence while considering other factors such as cultural and disease context, and the specific needs of different populations.
Recent findings add important evidence for the promotion of male circumcision in countries without well-established programmes for cervical screening. Additional interventions to reduce HPV infection, such as provision of vaccines for HPV prevention, will be essential to reduce invasive cervical cancer worldwide. Male circumcision is associated with slight reductions in high-risk HPV, while licensed HPV vaccines protect with high effectiveness against only a limited number of HPV types. Therefore the two interventions are likely to have important synergistic effects.
ARG is on a speaker's bureau and has served as a consultant to Merck & Co. ARG and AGN have received grant support from Merck & Co. GA has received travel support from GlaxoSmithKline and Roche.
1 Braithwaite J. Excess of salt in the diet a probable factor in the causation of cancer. Lancet 1901; 158: 1578-1580.
2 Boyd JT, Doll R. A study of the aetiology of carcinoma of the cervix uteri. Br J Cancer 1964; 13: 419-434.
3 Castellsague X, Bosch FX, Munoz N, et alfor the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 2002; 346: 1105-1112. Cro
4 Tobian AA, Serwadda D, Quinn TC, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med 2009; 360: 1298-1309.
5 Auvert B, Sobngwi-Tambekou J, Cutler E, et al. Effect of male circumcision on the prevalence of high-risk human papillomavirus in young men: results of a randomized controlled trial conducted in Orange Farm, South Africa. J Infect Dis 2009; 199: 14-19.
6 Bosch FX, Albero G, Castellsague X. Male circumcision, human papillomavirus and cervical cancer: from evidence to intervention. J Fam Plann Reprod Health Care 2009; 35: 5-7.
7 Gray RH, Serwadda D, Kong X, et al. Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda. J Infect Dis 2010; 201: 1455-1462.
8 Wawer MJ, Tobian AAR, Kigozi G, et al. Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda. Lancet 201110.1016/S0140-6736(10)61967-8. published online Jan 7.
9 Xu F, Markowitz LE, Sternberg MR, Aral SO. Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999-2004. Sex Transm Dis 2007; 34: 479-484.
10 Drain PK, Halperin DT, Hughes JP, Klausner JD, Bailey RC. Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries. BMC Infect Dis 2006; 6: 172. CrossRef | PubMed
11 Centers for Disease Control and Prevention. Trends in circumcisions among newborns. (accessed Nov 12, 2010).
12 Tobian AA, Gray RH, Quinn TC. Male circumcision for the prevention of acquisition and transmission of sexually transmitted infections: the case for neonatal circumcision. Arch Pediatr Adolesc Med 2010; 164: 78-84.
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