Human papillomavirus (HPV) infection has been established as the necessary cause of invasive cervical cancer in women. It is also an important cause of a fraction of vaginal, vulvar, oropharyngeal, and anal cancer in women as well as of anal, oropharyngeal, and penile cancer in men.1 HPV-infected men play a key role in the transmission of HPV infection to their female partners. HPV infection in men also causes genital warts2 and is associated with HPV infection3 and cervical cancer in their female partners.4 Interventions that reduce the risk of HPV infection in men may have a preventative impact on HPV-related diseases both in men and women.
The evidence for a beneficial effect of male circumcision (MC) on HIV infection has repeatedly been demonstrated in randomized controlled trials (RCTs).5–7 There is growing evidence that MC may also protect against HPV infection and related disease.8–12 Little is know about the natural history of HPV infection in men with only a few small prospective studies undertaken in Europe,13–15 Latin America,16 and the United States (US).17–19 Most published studies to date have been cross-sectional. A prior meta-analysis of 8 observational studies found no evidence of an association between MC and prevalent genital HPV.20 However, a reanalysis of the same studies found a strong protective effect (odds ratio [OR] = 0.56, 95% confidence interval [CI]: 0.39–0.82).21 Here, we present the first meta-analysis that includes for the first time data from 2 recently completed RCTs on MC, and adds 9 observational studies to assess the association between MC and genital HPV infection.
MATERIALS AND METHODS
Identification and Eligibility of Relevant Studies
A systematic MEDLINE search was conducted to identify case-control studies, cross-sectional studies, RCTs of MC or cohort studies that reported data on genital HPV and/or genital warts in men by MC status. Reports published from February 1971 up to August 31st, 2010 were included. The search was performed using the following terms: “Papillomaviridae,” “Circumcision, Male,” “condylomata acuminata,” “genital diseases, male.” In addition, reference lists of all relevant publications were examined.
Included studies had to meet the following criteria: (1) reporting of separate genital HPV and/or genital warts by MC status, (2) inclusion of a precise description of how MC status was ascertained (e.g., clinical examination or self-reported), (3) for studies on genital warts, lesions had to be identified by clinical examination, and for studies on genital HPV, detailed methodological description of genital sampling techniques, specimen collection, anatomical sites sampled, and details of the different polymerase chain reaction assays used for HPV DNA detection, and (4) inclusion of at least 15 circumcised or uncircumcised men.
We examined genital HPV and genital warts by MC status as the primary endpoint. In studies in which the outcome was genital HPV, we further examined genital HPV prevalence, acquisition, clearance, high-risk HPV prevalence, high-risk HPV acquisition, and high-risk HPV clearance as endpoints.
Data were extracted by an independent reviewer (G.A.) using a standardized format. Studies included were verified by a second reviewer (X.C.). The following data were extracted: first author, journal name, year of publication, country of study population, source of the study population, age range, study design, method of ascertaining MC status, proportion circumcised, sample size, outcome of interest, measure of association, crude and adjusted effects, and confounders adjusted for when available. In studies in which the outcome was genital HPV, data on the outcome, as well as the sampling method used, subsites sampled, and HPV DNA detection assay used were extracted. When key information was not available, missing data were requested from the authors.
Effect estimates were computed using hazard ratios (HR) for cohort studies, risk ratio (RR) for RCTs, and OR for cross-sectional studies, case series, and case-control studies. If the OR was not reported but the raw data were available, the OR and 95% CI were calculated manually. Effect estimates (adjusted when available) were included in random effects models. Heterogeneity between studies was tested using the Q statistic. Pooled effect estimates were derived from random effects models. Sensitivity analyses were conducted restricting meta-analysis by study design and HPV outcome.22 We assessed associations with 3 different genital HPV outcomes: HPV prevalence, HPV acquisition, and HPV clearance. Genital HPV acquisition was defined as the first positive HPV result after at least one negative result had been observed in a previous visit. Genital HPV clearance was defined as the absence of one or multiple HPV types that had been observed during the previous visit. Publication bias was evaluated visually using the funnel plot and statistically using both the Begg and the Egger tests of funnel plot for correlation between the effect estimates and their variances.23,24 The systematic review was performed according to the standards recommended by the Cochrane Collaboration. Statistical and graphical analyses were carried out using Stata 11.0 and R 2.11.125,26 following the PRISMA guidelines.27
Selection of Studies
In total, the MEDLINE database identified 995 individual publications, of which 37 articles included original data and were eligible for review. The remaining 958 publications were review articles and opinion pieces. Fourteen studies were finally excluded because they did not meet the pre-established inclusion criteria: 2 reported on other penile lesions,28,29 1 lacked description on how penile lesions were diagnosed,30 1 lacked description on how genital warts were diagnosed,31 6 were studies in which genital warts were not diagnosed by clinical examination,10,32–36 and 4 included fewer than 15 circumcised or uncircumcised men.37–40 A total of 21 studies (23 publications) were thus included in this meta-analysis, involving a total of 8046 circumcised and 6336 uncircumcised men.
Two RCTs investigating MC were identified. One was conducted in Orange Farm, South Africa.41 Although the primary endpoint was the acquisition of HIV the trial also investigated the association between MC and the prevalence of high-risk HPV. A total of 3274 uncircumcised men were randomized to a control or a MC intervention group with follow-up visits at months 3, 12, and 21. The meta-analysis included data from 1264 participants from whom a urethral swab sample was collected at the 21-month visit. The second RCT identified included 2 parallel but independent trials of MC in the prevention of HIV infection and other sexually transmitted infections and were conducted in Rakai, Uganda.42 The 2 trials had identical protocols. As a secondary objective the trial assessed the efficacy of MC in the prevention of HPV infections in HIV-negative men. A total of 3393 HIV-negative uncircumcised men were randomized to a control or a MC intervention group with follow-visits at months 6, 12, and 24. HPV was assessed in a subgroup of trial participants with 24 months follow-up. For our analysis, we included data on 520 participants from whom preputial and coronal sulcus swabs were collected and tested for HPV DNA detection.
Association Between MC and Genital HPV
Sixteen studies (18 publications), examined the association between MC and some measure of genital HPV infection. The studies were conducted in the US, Mexico, Africa, South Korea, Denmark, Canada, a multinational study conducted in Brazil, Colombia, Spain, Thailand, and the Philippines, and a multinational study conducted in Brazil, Mexico, and the US. The study populations included students, patients attending sexually transmitted disease or vasectomy clinics, military men, men from the general population, workers in the fishing industry, and husbands or stable partners of women with or without cervical cancer (Table 1).
Variability in methodologies such as sampling methods, HPV DNA detection assays, and specimen collection sites was observed. The most common sampling method to obtain exfoliated cells from the genital epithelium was swabs alone followed by the use of emery or textured paper and swabs, swabs and cytobrush, and cytobrush only. All studies used polymerase chain reaction to amplify HPV DNA. The majority of studies used the PGMY09/11 primer for HPV DNA detection. One multinational study used the MY09/11 primer for the samples collected from Colombia and Spain and the GP5+/6+ primer for the samples collected from Brazil, Thailand, and the Philippines. One study used the GP5+/6+ primer, 2 the Roche Amplicor HPV Test, and 1 the SPF10 primer. Samples were collected from various genital sites or a combination of sites. Fourteen studies collected samples from the glans, 13 from the penile shaft, and 12 from the corona sulcus, or scrotum. Nine studies collected samples from the foreskin, 8 from the urethra, and 3 from the perianal region. Samples from urine, semen, perianal region, anal canal, and fingernails were excluded from this meta-analysis (Table 2).
Association Between MC and Genital HPV Prevalence
Fourteen studies examined genital HPV prevalence by MC status.8,9,11,16–19,43–49 The proportion of men who were circumcised ranged from 7.2% to 88.3%. Study size ranged from 198 to 1139 men. Significant heterogeneity among studies that examined genital HPV prevalence was observed (Q statistic, P < 0.001). Overall, MC was associated with a significant reduced odds of genital HPV prevalence (OR = 0.57, 95% CI: 0.42–0.77) (Fig. 1, panel A). A similar inverse association was also statistically significantly observed for high-risk HPV genital prevalence as assessed in the 2 RCTs of MC, (RR = 0.67, 95% CI: 0.54–0.82).41,42 No heterogeneity between the 2 RCTs was observed (Q statistic, P = 0.84) (Fig. 1, panel A).
Association Between MC and Genital HPV Acquisition
Three cohort studies and 1 RCT examined the effect of MC on genital HPV acquisition of new HPV infections (Table 1).16,17,19,50 Time between the first HPV positive result after a negative result ranged from 4 to 24 months. No heterogeneity between the cohort studies was observed (Q statistic, P = 0.79). MC was not associated with risk of genital HPV acquisition (summary effect 1.01, 95% CI: 0.66–1.53) (Fig. 1, panel A).
Association Between MC and Genital HPV Clearance
Two cohort studies and 1 RCT examined the effect of MC on the rate of genital HPV clearance in men (Table 1).19,50,51 Time until the first HPV negative result after a positive result for 1 or multiple HPV types ranged from 1.3 to 42.1 months. Only 1 study limited analyses to incident HPV infections.51 Significant heterogeneity among cohort studies that examined genital HPV clearance was observed (Q statistic, P = 0.02). MC was not associated with genital HPV clearance (HR = 1.57, 95% CI: 0.51–4.89) (Fig. 1, panel A).
Sensitivity Analyses on the Association Between MC and Genital HPV
Sensitivity analyses by key methodological variables were performed. As shown in Table 3, regardless of inclusion of the penile shaft or the scrotum specimens, a consistent protective effect was found for the association between MC and genital HPV prevalence. MC was associated with a significant reduced odds of genital HPV prevalence among studies that sampled the penile shaft or the scrotum (OR = 0.61, 95% CI: 0.44–0.85). A protective effect between MC and genital HPV prevalence was observed among studies using physical examination for ascertainment of circumcision status (OR = 0.58, 95% CI: 0.42–0.81). However, MC was not associated with genital HPV prevalence among studies using self-reported circumcision status (OR = 0.50, 95% CI: 0.20–1.26). MC was associated with a significant reduced odds of genital HPV prevalence among studies that reported adjusted estimate effects (OR = 0.44, 95% CI: 0.30–0.64). In contrast, the inverse association was not significant among studies that did not adjust for potential confounders (OR = 0.79, 95% CI: 0.52–1.19).
MC was associated with a significant reduced risk of genital high-risk HPV acquisition among the RCT that used physical examination to ascertain circumcision status or did not sample that penile shaft or the scrotum (RR = 0.67, 95% CI: 0.50–0.91). MC was not associated with a reduced risk of genital HPV acquisition among cohort studies that sampled the penile shaft or the scrotum (summary effect 1.01, 95% CI: 0.66–1.53). Finally, MC was associated with a nonsignificant increased probability of genital HPV clearance among cohort studies that sampled the penile shaft or scrotum (HR = 1.57, 95% CI: 0.51–4.89) and a significant increased probability of genital high-risk HPV clearance among the RCT that did not sample the penile shaft or scrotum (RR = 1.39, 95% CI: 1.17–1.64).
Association Between MC and Genital Warts
Five studies of genital warts were identified, including 2 from Australia, 1 from England, 1 from Africa, and 1 from the US.52–56 Four studies recruited men attending sexually transmitted disease clinics and 1 recruited HIV-seronegative truck drivers. The proportion of circumcised men ranged from 24.0% to 87.3%. Study size ranged from 263 to 2776 men. Only 2 studies adjusted for key covariates that were potential confounders (Table 4). Significant heterogeneity among studies of genital warts was observed (Q statistic, P = 0.02). MC was not associated with genital warts (OR = 0.89, 95% CI: 0.59–1.33) (Fig. 1, panel B).
Assessment of Publication Bias
We found no evidence of publication bias among the 21 studies included (Egger test P = 0.15). Consistent with this, the funnel plot was not asymmetric (Fig. 2). We also found no evidence of publication bias for each genital outcome studied: warts studies (P = 0.26), HPV prevalence studies (P = 0.32), HPV acquisition studies (P = 0.18), and HPV clearance studies (P = 0.84). Furthermore, we found no evidence of publication bias among studies that did not meet the inclusion criteria in this meta-analysis for reporting on other penile lesions28,29 and those that included fewer circumcised or uncircumcised men, if data were available (P = 0.69).37–40 Similar results were found using Begg test. Consistent with these results the funnel plot for each outcome was not asymmetric (data not shown).
Results of this meta-analysis, which includes data from case-control, cross-sectional, cohort, and RCTs studies, show that MC is associated with an overall reduction in the prevalence of genital HPV infection in men.8,9,11,16,19,41,42,45,48
Few studies have evaluated the association between MC and acquisition of new genital HPV infections or HPV clearance which require a prospective design. However, one RCT conducted in Uganda showed that MC was associated with a significant reduction in the acquisition of new genital high-risk HPV infections.50 These findings are consistent with the observed reduction in the prevalence of high-risk HPV in 2 RCTs41,42 and in several observational studies.8,9,11,16,19,45,48 In contrast, 3 observational prospective studies16,17,19 found inconsistent results with an overall nonsignificant pooled estimate effect for the association between MC and genital HPV acquisition risk.
Consistent with the association observed between MC and HPV acquisition, one RCT conducted in Uganda, also showed a statistically significant increase in the clearance of high-risk HPV infections with MC.50 This finding was also consistent with the results from a small US cohort study.19 However, the overall pooled estimate of the association between MC and HPV clearance did not reach statistical significance. The influence that MC may have on HPV clearance may be dependent on the genital site examined as one study found a significant increased rate of HPV clearance of high-risk HPV infection when only the glans or coronal sulcus were examined.51 Further, the RCT conducted in Uganda sampled the glans and coronal sulcus only and demonstrated also an increased genital high-risk HPV clearance with MC. Another study observed greater clearance of high-risk HPV infections as well as any HPV infections.19 However, site-specific estimations are rarely reported in the literature.
When interpreting the results of this meta-analysis, importance should be given to the consistent results derived from RCTs of MC, in which significant associations were found for all 3 HPV outcomes.41,42,50 The consistency of results when restricting the data to RCTs is relevant as it is well accepted that this study design provides the strongest evidence with which to draw conclusions regarding causality. However, all RCTs were conducted among African adult men and caution should be taken in generalizing these results to other populations, including infants.
In this meta-analysis, the inverse association between MC and genital warts prevalence was not statistically significant. Only 5 studies were included, of which 2 did report that MC status influenced the distribution of warts on the penis. One study found that uncircumcised men were more likely to present with distal lesions and circumcised men with proximal lesions on the penis.57 Another study found that extensive wart formations were more common in uncircumcised men.52 The lack of a strong effect of MC on genital warts may be because these lesions often appear on the penile shaft, a site for which circumcision is unlikely to strongly influence.58 Additional studies are necessary to investigate if circumcision status affects the risk and distribution of warts on the penis.
The mechanism by which circumcision might protect against HPV infection is unclear. The penile shaft and the outer surface of the foreskin are covered by a keratinized stratified squamous epithelium that provides a protective barrier against HPV infection. In contrast, the mucosal lining of the prepuce is not keratinized and might be more susceptible to the virus.9,59 In uncircumcised men, the foreskin is pulled back during intercourse, and the inner mucosa surface of the prepuce is exposed to vaginal and cervical secretions. It has been proposed that retraction of the foreskin during intercourse exposes the inner mucosal surface to HPV providing access to the basal cells through small abrasions.9,18,60,61 Removal of the foreskin thus could minimize the chance of viral entrance as a result of both the reduced size of the mucosal surface area vulnerable to HPV and the increased chance of mucosal trauma during intercourse.9 Thus, it is plausible that circumcision might reduce high-risk HPV acquisition.50 It is not understood how circumcision facilitates greater clearance of HPV. It has been proposed that HPV enters and persists more efficiently in the inner mucosal surface of the prepuce of uncircumcised men than in the keratinized penile surface of circumcised men.51
There are a number of limitations that must be considered in interpreting these results. One is the variability in study designs and sampling methodologies across studies. Sensitivity analyses were carried out restricting the meta-analysis by study design and genital HPV outcome studied: warts, HPV prevalence, HPV acquisition studies, and HPV clearance to examine the robustness of the pooled results. In all analyses, a consistent inverse association of MC with genital HPV prevalence was observed. Another limitation is that a substantial proportion of the included published studies were cross-sectional, which limits the causality inference of MC on HPV infection. However, similar to what has been observed in cross-sectional studies, 2 RCTs have consistently shown an association between MC and lower risk of genital HPV infection. Another limitation is a possible selection bias in the studies we included in this meta-analysis. However, publication bias was not observed. Although this meta-analysis included studies from several countries, it is possible that our results may not be generalizable to all men. Finally, there may be other factors that could influence the association between MC and HPV infection that were not considered in our analysis, such as the effect of age at circumcision or the surgical procedure used to remove the prepuce.
There is literature to suggest that MC for the prevention of HIV infection is cost-effective across a broad range of age groups in Africa.62 Ideally, MC should be a procedure conducted before potential exposure to HPV through sexual contact. However, this recommendation should be consistent with other factors such as the culture and the specific needs of different populations.
In conclusion, this meta-analysis shows a robust inverse association between MC and genital HPV prevalence in men. Additional studies that include diverse populations and data on HPV acquisition, clearance, or both in men are necessary to more clearly define how MC reduces genital HPV prevalence in men and to address the limitations of the current study. Given the consistent protective effects also found for HIV, MC should be considered as an additional one-time preventative intervention likely to reduce the burden of associated diseases in both men and women, particularly among those countries in which HPV vaccination programs and cervical cancer screening are not available.
1. Munoz N, Castellsague X, de Gonzalez AB, et al.. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006; 24(suppl 3): S3/1–10.
2. Giuliano AR, Tortolero-Luna G, Ferrer E, et al.. Epidemiology of human papillomavirus infection in men, cancers other than cervical and benign conditions. Vaccine 2008; 26:(suppl10): K17–K28.
3. Burchell AN, Winer RL, de Sanjose S, et al.. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine 2006; 24(suppl 3): S3/52–61.
4. Bosch FX, de Sanjose S. The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers 2007; 23: 213–227.
5. Auvert B, Taljaard D, Lagarde E, et al.. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med 2005; 2: e298.
6. Bailey RC, Moses S, Parker CB, et al.. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial Lancet 2007; 369: 643–656.
7. Gray RH, Kigozi G, Serwadda D, et al.. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial Lancet 2007; 369: 657–666.
8. Baldwin SB, Wallace DR, Papenfuss MR, et al.. Condom use and other factors affecting penile human papillomavirus detection in men attending a sexually transmitted disease clinic. Sex Transm Dis 2004; 31: 601–607.
9. Castellsague X, Bosch FX, Munoz N, et al.. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 2002; 346: 1105–1112.
10. Daling JR, Madeleine MM, Johnson LG, et al.. Penile cancer: Importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer 2005; 116: 606–616.
11. Svare EI, Kjaer SK, Worm AM, et al.. Risk factors for genital HPV DNA in men resemble those found in women: A study of male attendees at a Danish STD clinic. Sex Transm Infect 2002; 78: 215–218.
12. Tsen HF, Morgenstern H, Mack T, et al.. Risk factors for penile cancer: Results of a population-based case-control study in Los Angeles County (United States). Cancer Causes Control 2001; 12: 267–277.
13. Van Doornum GJ, Prins M, Juffermans LH, et al.. Regional distribution and incidence of human papillomavirus infections among heterosexual men and women with multiple sexual partners: A prospective study. Genitourin Med 1994; 70: 240–246.
14. Wikstrom A, Popescu C, Forslund O. Asymptomatic penile HPV infection: A prospective study. Int J STD AIDS 2000; 11: 80–84.
15. Kjaer SK, Munk C, Winther JF, et al.. Acquisition and persistence of human papillomavirus infection in younger men: A prospective follow-up study among Danish soldiers. Cancer Epidemiol Biomarkers Prev 2005; 14: 1528–1533.
16. Lajous M, Mueller N, Cruz-Valdez A, et al.. Determinants of prevalence, acquisition, and persistence of human papillomavirus in healthy Mexican military men. Cancer Epidemiol Biomarkers Prev 2005; 14: 1710–1716.
17. Partridge JM, Hughes JP, Feng Q, et al.. Genital human papillomavirus infection in men: Incidence and risk factors in a cohort of university students. J Infect Dis 2007; 196: 1128–1136.
18. Hernandez BY, Wilkens LR, Zhu X, et al.. Circumcision and human papillomavirus infection in men: A site-specific comparison. J Infect Dis 2008; 197: 787–794.
19. Lu B, Wu Y, Nielson CM, et al.. Factors associated with acquisition and clearance of human papillomavirus infection in a cohort of US men: A prospective study. J Infect Dis 2009; 199: 362–371.
20. Van Howe RS. Human papillomavirus and circumcision: A meta-analysis. J Infect 2007; 54: 490–496.
21. Castellsague X, Albero G, Cleries R, et al.. HPV and circumcision: A biased, inaccurate and misleading meta-analysis. J Infect 2007; 55: 91–93; author reply: 93–96.
22. Petitti DB. Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. 2nd ed. New York, NY: Oxford University Press, 2000.
23. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–1101.
24. Egger M, Davey Smith G, Schneider M, et al.. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.
25. StataCorp. 2007. Stata Statistical Software: Release 10. College Station, TX: StataCorp LP.
26. R Development Core Team (2010). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. URL: http://www.R-project.org
27. Moher D, Liberati A, Tetzlaff J, et al.. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009; 6: e1000097.
28. Aynaud O, Ionesco M, Barrasso R. Penile intraepithelial neoplasia. Specific clinical features correlate with histologic and virologic findings. Cancer 1994; 74: 1762–1767.
29. Aynaud O, Piron D, Bijaoui G, et al.. Developmental factors of urethral human papillomavirus lesions: Correlation with circumcision. BJU Int 1999; 84: 57–60.
30. Mallon E, Hawkins D, Dinneen M, et al.. Circumcision and genital dermatoses. Arch Dermatol 2000; 136: 350–354.
31. Wilson RA. Circumcision and venereal disease. Can Med Assoc J 1947; 56: 54–56.
32. Dave SS, Fenton KA, Mercer CH, et al.. Male circumcision in Britain: Findings from a national probability sample survey. Sex Transm Infect 2003; 79: 499–500.
33. Dinh TH, Sternberg M, Dunne EF, et al.. Genital warts among 18- to 59-year-olds in the United States, national health and nutrition examination survey, 1999–2004. Sex Transm Dis 2008; 35: 357–360.
34. Klavs I, Hamers FF. Male circumcision in Slovenia: Results from a national probability sample survey. Sex Transm Infect 2008; 84: 49–50.
35. Richters J, Smith AM, de Visser RO, et al.. Circumcision in Australia: Prevalence and effects on sexual health. Int J STD AIDS 2006; 17: 547–554.
36. Thomas DB, Ray RM, Pardthaisong T, et al.. Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand. Am J Epidemiol 1996; 143: 779–786.
37. Bleeker MC, Hogewoning CJ, Voorhorst FJ, et al.. HPV-associated flat penile lesions in men of a non-STD hospital population: Less frequent and smaller in size than in male sexual partners of women with CIN. Int J Cancer 2005; 113: 36–41.
38. Kjaer SK, de Villiers EM, Dahl C, et al.. Case-control study of risk factors for cervical neoplasia in Denmark. I: Role of the ”male factor“ in women with one lifetime sexual partner Int J Cancer 1991; 48: 39–44.
39. Nicolau SM, Camargo CG, Stavale JN, et al.. Human papillomavirus DNA detection in male sexual partners of women with genital human papillomavirus infection. Urology 2005; 65: 251–255.
40. Rombaldi RL, Serafini EP, Villa LL, et al.. Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia. Braz J Med Biol Res 2006; 39: 177–187.
41. 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.
42. 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.
43. Shin HR, Franceschi S, Vaccarella S, et al.. Prevalence and determinants of genital infection with papillomavirus, in female and male university students in Busan, South Korea. J Infect Dis 2004; 190: 468–476.
44. Weaver BA, Feng Q, Holmes KK, et al.. Evaluation of genital sites and sampling techniques for detection of human papillomavirus DNA in men. J Infect Dis 2004; 189: 677–685.
45. Vaccarella S, Lazcano-Ponce E, Castro-Garduno JA, et al.. Prevalence and determinants of human papillomavirus infection in men attending vasectomy clinics in Mexico. Int J Cancer 2006; 119: 1934–1939.
46. Nielson CM, Flores R, Harris RB, et al.. Human papillomavirus prevalence and type distribution in male anogenital sites and semen. Cancer Epidemiol Biomarkers Prev 2007; 16: 1107–1114.
47. Ng'ayo MO, Bukusi E, Rowhani-Rahbar A, et al.. Epidemiology of human papillomavirus infection among fishermen along Lake Victoria Shore in the Kisumu District, Kenya. Sex Transm Infect 2008; 84: 62–66.
48. Giuliano AR, Lazcano E, Villa LL, et al.. Circumcision and sexual behavior: Factors independently associated with human papillomavirus detection among men in the HIM study. Int J Cancer 2009; 124: 1251–1257.
49. Ogilvie GS, Taylor DL, Achen M, et al.. Self-collection of genital human papillomavirus specimens in heterosexual men. Sex Transm Infect 2009; 85: 221–225.
50. 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.
51. Hernandez BY, Shvetsov YB, Goodman MT, et al.. Reduced clearance of penile human papillomavirus infection in uncircumcised men. J Infect Dis 2010; 201: 1340–1343.
52. Oriel JD. Natural history of genital warts. Br J Vener Dis 1971; 47: 1–13.
53. Parker SW, Stewart AJ, Wren MN, et al.. Circumcision and sexually transmissible disease. Med J Aust 1983; 2: 288–290.
54. Cook LS, Koutsky LA, Holmes KK. Circumcision and sexually transmitted diseases. Am J Public Health 1994; 84: 197–201.
55. Donovan B, Bassett I, Bodsworth NJ. Male circumcision and common sexually transmissible diseases in a developed nation setting. Genitourin Med 1994; 70: 317–320.
56. Lavreys L, Rakwar JP, Thompson ML, et al.. Effect of circumcision on incidence of human immunodeficiency virus type 1 and other sexually transmitted diseases: A prospective cohort study of trucking company employees in Kenya. J Infect Dis 1999; 180: 330–336.
57. Cook LS, Koutsky LA, Holmes KK. Clinical presentation of genital warts among circumcised and uncircumcised heterosexual men attending an urban STD clinic. Genitourin Med 1993; 69: 262–264.
58. 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.
59. Hussain LA, Lehner T. Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. Immunology 1995; 85: 475–484.
60. Szabo R, Short RV. How does male circumcision protect against HIV infection? BMJ 2000; 320: 1592–1594.
61. Weiss HA, Thomas SL, Munabi SK, et al.. Male circumcision and risk of syphilis, chancroid, and genital herpes: A systematic review and meta-analysis. Sex Transm Infect 2006; 82: 101–109; discussion 110.
62. Binagwaho A, Pegurri E, Muita J, et al.. Male circumcision at different ages in Rwanda: A cost-effectiveness study. PLoS Med 2010; 7: e1000211.