NEW ENGLAND JOURNAL OF MEDICINE, Volume 347, Number 18: Page 1448,
October 31, 2002.

Letters to the Editor:

Male Circumcision, Penile Human Papillomavirus Infection, and Cervical Cancer

To the Editor: Castellsagué et al. (April 11 issue) [1] did not correct for several of the major known risk factors for cervical cancer: race or ethnic group, smoking, human immunodeficiency virus (HIV) infection, poor diet, long-term use of oral contraceptives, and low socioeconomic status. [2] Samples for testing for human papillomavirus (HPV) were obtained by intraurethral swabbing and swabbing of the external surface of the glans and coronal sulcus. This surface is dry on circumcised penises but moist on intact penises, increasing the likelihood of detection of HPV regardless of the actual rate of infection.

In other work involving the same participants, the HPV genotypes in the men did not match those in their partners. This finding strongly suggests that the relation between HPV in men and that in their partners was not one of simple transmission. [3]

John W. Travis, M.D., M.P.H.
Alliance for Transforming the Lives of Children
Charlottesville, VA 22903


  1. Castellsagué X, Bosch FX, Muñoz N, et al. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 2002;346:1105-1112.
  2. What are the risk factors for cervical cancer? Atlanta: American Cancer Society, 2002. (Accessed October 10, 2002)
  3. Franceschi S, Castellsagué X, Dal Maso L, et al. Prevalence and determinants of human papillomavirus genital infection in men. Br J Cancer 2002;86:705-711.

To the Editor: Castellsagué et al. present evidence that male circumcision is associated with reduced risks of penile HPV infection and cervical cancer in female partners. They theorize that removal of the foreskin "markedly decreases" both the surface area susceptible to HPV infection and the likelihood of mucosal trauma during intercourse. However, the mucosal surface of the foreskin has been described as a "specific erogenous zone" [1] and an "important component of the overall sensory mechanism of the human penis." [2] Prudence dictates that before promoting circumcision as preventive treatment against disease, researchers should confirm that the procedure is ethically appropriate and has no adverse long-term effects on sexual sensation or function.

Arif Bhimji, M.D.
Dennis Harrison
Association for Genital Integrity
Vancouver, BC V5Z 4R3, Canada


  1. Winkelmann RK. The erogenous zones: their nerve supply and its significance. Mayo Clin Proc 1959;34:39-47.
  2. Taylor JR, Lockwood AP, Taylor AJ. The prepuce: specialized mucosa of the penis and its loss to circumcision. Br J Urol 1996;77:291-295.

The authors reply:

To the Editor: Travis raises the issue that potential confounding could explain the inverse association between male circumcision and the risk of cervical cancer in female partners. In fact, the addition to our final logistic-regression model of the race or ethnic background of monogamous female partners and their smoking status, use of oral contraceptives, and level of education lowered the odds ratio for cervical cancer from 0.75 to 0.64 (95 percent confidence interval, 0.39 to 1.04), thus showing an even stronger inverse association. Information on HIV status and diet was not collected in this study, but for these variables to be considered true confounders, they must be related both to circumcision status (which is very unlikely in the case of diet) and to cervical cancer. Although HIV status and circumcision status might be associated with one another, HIV infection alone is not considered a cause of cervical cancer. Furthermore, estimates of the prevalence of HIV infection in the populations we studied were too low to explain the associations we found.

Travis also suggests that the association might be explained by potential HPV-DNA-detection bias introduced by circumcision. Although it is plausible that circumcision compromises cellular yield, the quality and sensitivity of our polymerase chain reaction overcome this potential limitation. We used amplification of a fragment of the -globin gene as an internal quality control for each specimen, thus ensuring both the high quality of the DNA and the presence of cells. Samples from which the -globin and HPV L1 genes could not be amplified were excluded from the analyses, and no differences were found between the subjects with such samples and those with valid samples. Finally, we admit that the lack of correlation of HPV genotypes between the two partners [1] is puzzling, but it should not call into question our findings regarding circumcision, since the study involving couples provided information only on the HPV status of each partner at the time of the sampling.

We thank Bhimji and Harrison for reminding us that circumcision may have other consequences, since the procedure removes an important erogenous zone; this and other "noninfectious" considerations should also be taken into account before any recommendations are made. Since we received numerous letters (and even a targeted, data-damaging cyberattack) from pro- and anti-circumcision groups, we would like to emphasize that our study was not intended to provide global evidence against or in favor of recommending circumcision. Nevertheless, we still think that there is a need for a comprehensive multidisciplinary review that considers all aspects of male circumcision and identifies which kinds of studies are still required in order to elaborate evidence-based recommendations regarding this controversial issue.

Xavier Castellsagué, M.D.
F. Xavier Bosch, M.D.
Institut Català d'Oncologia
08907 Barcelona, Spain

Nubla Muñoz, M.D.
International Agency for Research on Cancer
69372 Lyons CEDEX 8, France


  1. Franceschi S, Castellsagué X, Dal Maso L, et al. Prevalence and determinants of human papillomavirus genital infection in men. Br J Cancer 2002;86:705-711.

(File revised 21 November 2006)