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Robert S. Van Howe, Sampling Bias Explains Association between Human Papillomavirus and Circumcision, The Journal of Infectious Diseases, Volume 200, Issue 5, 1 September 2009, Page 832, https://doi.org/10.1086/605020
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Extract
To the Editor—I read with interest the recent study of human papillomavirus (HPV) infection and circumcision by Auvert et al [1]. Although the authors believe they have demonstrated that circumcision prevents HPV infection, their findings can be completely attributed to sampling bias, which the authors fail to consider
The authors chose to sample only the urethra for HPV, stating that “[t]he urethra was chosen because the detection of HPV in this anatomical site is probably not affected by circumcision status” [1, p 15]. Unfortunately, several studies have demonstrated that the yield of HPV cultures differs at various locations on the penis depending on circumcision status [2–6 ]. Most notably, HPV is more likely to be cultured from the shaft of the circumcised penis and from the glans of the normal penis. Weaver et al [2] found that, among men who had HPV recovered from any of numerous locations, 48% of circumcised men and 65% of uncircumcised men had a positive glans culture result. This indicates that an infected man with an uncircumcised penis for whom only the glans was cultured would be 1.35 times more likely to have a positive result than would an infected man with a circumcised penis. If the numbers of Auvert and colleagues are adjusted for this difference in yield, their findings are less dramatic and are no longer statistically significant (intention-to-treat odds ratio [OR], 0.87 [95% confidence interval {CI}, 0.66–1.14]; as-treated OR, 0.77 [95% CI, 0.59–1.01])
