Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort

Dickson, Nigel; Ryding, Janka; Roode, Thea van; Paul, Charlotte; Herbison, Peter; Dillner, Joakim; Skegg, D. C. G.

doi:10.1158/1055-9965.epi-08-0353

Cited by 19 publications

(10 citation statements)

References 48 publications

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“…15-16 Many of these observational studies had limited power, were vulnerable to confounding by sexual behaviors in men and women, and evaluated MC status by self-report or the female partner’s report. Moreover, the long latent interval between initial HR-HPV infection and the development of cervical neoplasia complicates causal inferences from retrospective data on prior exposures.…”

Section: Introductionmentioning

confidence: 99%

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

et al. 2011

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Background Randomized trials show that medical male circumcision (MC) reduces high-risk human papillomavirus (HR-HPV) infection in men. We assessed the efficacy of MC to reduce HR-HPV in female partners. Methods HIV-negative men were randomized to immediate MC (intervention) or MC delayed for 24 months (control). HIV-uninfected female partners of married men (648 intervention and 597 control arm) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 and 24 months. Female HPV infection was a secondary trial end point. Vaginal swabs were evaluated for HR-HPV by Roche HPV Linear Array. An intention-to-treat analysis estimated prevalence risk and incident rate ratios (PRR and IRR) and 95% confidence intervals (95%CI) of HR-HPV by Poisson multiple regression. In women with pre-existing HR-HPV, we estimated the risk ratio (RR) of cleared infection (i.e., loss of detection). The trials were registered with ClinicalTrials.gov, NCT00425984 and NCT00124878.) Findings Female characteristics and HPV prevalence were similar between arms at enrollment. Two year retention rates were 84.7% (549/648) in intervention arm and 84.1% (502/597) in control arm spouses. Year 2 female HR-HPV prevalence was 27.8% (151/544) in the intervention and 38.7% (189/488) in the control arm (PRR=0.72, 95%CI 0.60–0.85, p=0.001). HR-HPV incidence was 20.7/100py in the intervention arm and 26.9/100py in the control arm wives (IRR=0.77, 95%CI 0.63-0.93, p=0.008). HR-HPV incidence was lower in intervention than control arm wives for 13 of 14 (92.9%) HR-HPV genotypes and in most demographic/behavioral subgroups. Genotype specific HR-HPV clearance was higher in the wives of men in the intervention arm (66.2%, 376/568) than the control arm (59.2%, 339/573, RR=1.12, 95%CI 1.02-1.22). Interpretation MC reduces the prevalence and incidence and increases clearance of HR-HPV infections in female partners. Funding Bill & Melinda Gates Foundation with additional laboratory and training support from National Institutes of Health and Fogarty International Center.

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Section: Introductionmentioning

confidence: 99%

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

et al. 2011

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“…A metaanalysis of circumcision status and HPV infection that used metaregression also demonstrated that finding an association between HPV and circumcision status was less likely in studies in which sampling the shaft of penis for HPV was performed [7]. A recently published birth cohort study from New Zealand found that the combined seroprevalence of HPV-16 and HPV-18 was not affected by circumcision status (OR, 1.2 [95% CI, 0.75-1.9]) [8]. When studies published since the metaanalysis are included [1,5,6,8] and the analysis is repeated using metaregression, not ascertaining circumcision status by physical examination (OR, 1.77 [95% CI, 1.15-2.73]) and not sampling the penile shaft (OR, 1.57 [95% CI, 1.16-2.12]) are both significantly associated with finding an association between circumcision status and HPV infection.…”

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confidence: 99%

“…A recently published birth cohort study from New Zealand found that the combined seroprevalence of HPV-16 and HPV-18 was not affected by circumcision status (OR, 1.2 [95% CI, 0.75-1.9]) [8]. When studies published since the metaanalysis are included [1,5,6,8] and the analysis is repeated using metaregression, not ascertaining circumcision status by physical examination (OR, 1.77 [95% CI, 1.15-2.73]) and not sampling the penile shaft (OR, 1.57 [95% CI, 1.16-2.12]) are both significantly associated with finding an association between circumcision status and HPV infection. Adjusting for these 2 factors, the summary OR for circumcision is 0.91 (95% CI, 0.74-1.11), and the difference is not statistically significant.…”

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confidence: 99%

Sampling Bias Explains Association between Human Papillomavirus and Circumcision

Howe

2009

J INFECT DIS

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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][3][4][5][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]).Auvert and colleagues state that their findings are consistent with those of other studies, yet these studies likewise fail to address sampling bias. For example, Hernandez et al [5] found that oncogenic HPV was more common on the glans of men with an uncircumcised penis; however, when oncogenic HPV obtained from any site is considered, no difference is seen (OR, 0.88 [95% CI, 0.45-1.74]). A metaanalysis of circumcision status and HPV infection that used metaregression also demonstrated that finding an association between HPV and circumcision status was less likely in studies in which sampling the shaft of penis for HPV was performed [7]. A recently published birth cohort study from New Zealand found that the combined seroprevalence of HPV-16 and HPV-18 was not affected by circumcision status (OR, 1.2 [95% CI, 0.75-1.9]) [8]. When studies published since the metaanalysis are included [1, 5, 6, 8] and the analysis is repeated using metaregression, not ascertaining circumcision status by physical examination (OR, 1.77 [95% CI, 1.15-2.73]) and not sampling the penile shaft (OR, 1.57 [95% CI, 1.16-2.12]) are both significantly associated with finding an association between circumcision status and HPV infection. Adjusting for these 2 factors, the summary OR for circumcision is 0.91 (95% CI, 0.74-1.11), and the difference is not statistically significant.When Auvert and colleagues chose to sample only the urethra, sampling bias guaranteed that their study would find a negative association between circumcision status and HPV infection. Conseq...

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“…Dave et al Guideline: Foreskin care and neonatal circumcision Dickson et al followed 450 children from birth in a cohort study conducted in New Zealand up to 32 years of age with circumcision status reported by mothers at 3 years of age [98]. Sexual behavior was recorded at 21, 26 and 32 years along with assessment of socioeconomic and moral-religious emphasis of family.…”

Section: Cuaj -Guidelinementioning

confidence: 99%

CUA guideline on the care of the normal foreskin and neonatal circumcision in Canadian infants

Davé

Afshar

Braga

et al. 2017

CUAJ

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Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort

Cited by 19 publications

References 48 publications

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda

Sampling Bias Explains Association between Human Papillomavirus and Circumcision

CUA guideline on the care of the normal foreskin and neonatal circumcision in Canadian infants

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