The role of circumcision,tobacco,and alcohol use in genital human papillomavirus infection among men from Denmark

Abstract

It is crucial to understand the natural history of genital human papillomavirus (HPV) infection in men to prevent the increasing male HPV-related disease burden. We evaluated the associations between HPV infection and circumcision, smoking, and alcohol use after accounting for sexual behavior. The study included 2331 male personnel from Danish barracks. Penile swabs were tested for HPV DNA with a polymerase chain reaction assay, INNO-LiPA. All men completed a self-administered questionnaire providing data on potential risk factors for HPV such as lifestyle and sexual habits. Using multivariable logistic regression, associations between potential risk factors and HPV infection were estimated and expressed as odds ratios (ORs) with 95% confidence intervals (CI). Current cigarette smoking was associated with increased odds of HPV detection (OR = 1.2; 95% CI: 1.0–1.4), but we found no association with alcohol use in the analysis adjusted for sexual behavior. Circumcision reduced the odds of a prevalent HPV infection (OR = 0.7; 95% CI: 0.5–1.0) although not statistically significantly. Strong associations with lifetime and recent number of female sex partners were observed, but in contrast to uncircumcised men, increasing number of sex partners was not associated with higher HPV prevalence in circumcised men. In conclusion, smoking was associated with increased odds of penile HPV in men from the general population in Denmark, whereas circumcision seemed to reduce the risk. Moreover, our results indicated that there might be differences in the viral susceptibility between circumcised and uncircumcised men.

Keywords

Human papillomavirus population-based risk factors circumcision

Introduction

With an estimated 80% of sexually active individuals acquiring human papillomavirus (HPV) infection at some point in their life, HPV is considered the commonest sexually transmitted infection worldwide.¹ In both sexes, HPV infection contributes to a considerable disease burden including genital warts, precancerous lesions, and cancer.² Although most HPV infections are transient and asymptomatic, some persist and can ultimately cause disease in the affected area.^3–5 In men, persistent infection with specific high-risk (HR) HPV types is associated with penile and anal precancerous lesions as well as penile, anal, and oropharyngeal cancer.^4,6 Moreover, presence of genital warts, which are primarily caused by low-risk (LR) HPV types 6 and 11, is a more common clinical manifestation in both men and women.⁷ In addition, precancerous lesions and cancer of the cervix, vulva, and vagina are HPV-associated diseases in women also constituting a large disease burden.^3,5

Knowledge about risk factors for HPV infection is important to understand the natural history of the infection. The risk factors of genital HPV infection in women are well studied, and data on men are accumulating. Sexual behavior factors, including age at first sexual intercourse, lifetime, and recent number of sex partners are strongly associated with risk of HPV infection.^6,8–17 It has also been suggested that other factors such as circumcision, tobacco, and alcohol use influence the risk. Some studies have found that male circumcision is associated with a reduced risk of HPV infection^11,18–20 including a recent meta-analysis.²¹ Nevertheless, the literature is not entirely consistent and not all studies have found this association.^14,22 Furthermore, it has been reported that circumcision can alter or modify the effect of other risk factors, such as number of partners.²³

Being a current cigaret smoker has previously been associated with increased persistence and prevalence of HPV infections in men both any HPV type, only HR HPV and also multiple infections.^14,24–28 Data on the potential role of alcohol use and genital HPV prevalence are still limited, and results are equivocal.^25,29,30 Moreover, the mechanisms behind these associations are still uncertain; biological mechanisms causing changed susceptibility to the virus has been proposed as well as smoking and drinking being a proxy for unmeasured sexual behavior.^25,31 Even though the majority of studies have adjusted for various sexual variables, there is no consensus on how to adjust for factors associated with sexual behavior in the published literature.

The objective of the this study was to assess the risk of HPV infection associated with circumcision, smoking, and alcohol intake after taking into account sexual behavior. In conjunction with this, we investigated whether the number of female sex partners was as an important risk determinant in circumcised as in uncircumcised men.

Methods

Details on this cross-sectional study have been described previously.³² Briefly, male personnel at a number of military barracks in Denmark were invited to participate in the study. All men received approximately €25 for their participation and gave their informed consent. The Regional Committee of the Capital Region on Health Research Ethics, the Danish Data Protection Agency, and the Danish Armed Forces Health Services approved the study.

The 2460 men enrolled in the study were 18–65 years. The men completed a self-administered questionnaire with detailed information about sociodemographic characteristics, smoking and drinking habits, sexual behavior, and history of sexually transmitted infections. Furthermore, the men went through a clinical examination by a male physician who assessed the circumcision status, the presence of genital warts, and other visible genital lesions. At the examination, cell scrapes for HPV DNA testing were collected from the penis (glans, sulcus coronaries, preputial cavity, shaft, and scrotum) with two pre-wetted cotton-tipped swabs. Both swabs were placed in the same tube, stored at 4°C, and sent to Germany at the Department of Experimental Virology, University of Tübingen, for HPV testing.

HPV testing and genotyping

Samples were tested parallel for the presence of HPV DNA by the Hybrid Capture 2 (HC2) method (QIAGEN, Hilden, Germany) and the LiPAv2 method (Fujirebio, Gent, Belgium) a polymerase chain reaction (PCR)–based method. Only the PCR-based results were used in this study. The PCR method used detects 24 HPV types, HR types HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68, and LR types HPV 6, 11, 40, 42, 43, 44, 54, 70 and 74. HPV positive samples with no detectable specific HPV type were denoted HPVX.

Statistical analysis

We used multivariable logistic regression to examine the association between the different exposure variables (circumcision, smoking, and alcohol use) and the odds of being HPV positive. The HPV-positive category included men who were positive for at least one HR or LR type, as well as HPVX-positive men. Associations were estimated as odds ratios (ORs) with 95% confidence intervals (CIs). All models were adjusted for age included as a continuous variable. To take into account confounding from sexual behavior, we initially selected five sexual behavior variables that according to the current literature are associated with genital HPV. The selected variables were age at first sexual intercourse with a woman, lifetime number of female sex partners, number of female sex partners the past 12 months (recent female sex partners), time since last intercourse with a woman, and condom use the past 12 months. To minimize the degrees of freedom on adjustment for sexual behavior, we applied backward stepwise regression including all five sexual behavior variables in age-adjusted models modelling age at first sexual intercourse with a women and lifetime and recent number of female partners as continuous variables. When the five sexual behavior variables were mutually and age-adjusted, only the variables age at sexual debut with a women, lifetime number of female sex partners, and time since last sexual intercourse were statistically significantly associated with HPV and were used for adjustment in the analysis examining circumcision, smoking, and alcohol use.

Next, we examined the risk factors circumcision, smoking, and alcohol use in separate models adjusting for age and sexual behavior. Alcohol use was specified as number of episodes of binge drinking per month, defined as intake of more than six units of alcohol at the same occasion, and categorized as ≤ 1 time, 2–3 times, or ≥ 4 episodes per month. Smoking status was categorized into never, former, and current smoking. In addition, we also considered number of cigarettes smoked per day, categorized as never and former, ≤ 10, 11–19, and ≥ 20. Finally, we examined the association between recent as well as lifetime number of female sex partners and HPV prevalence in subgroups by circumcision status by stratifying providing separate parameter estimates.

All analyses were done using the SAS Enterprise Guide versions 5.1 and 7.1.

Results

Among the 2460 men included in the study, 24 had samples with insufficient material for HPV analysis. In addition, for the present analysis, 105 men with incomplete information on the five sexual behavior variables were excluded, leaving 2331 men eligible for analysis. The mean age was 23 years (median, 20 years; range 18–59), the majority were single (67.6%), and 53.1% had more than 12 years of education. Approximately 5% of the study population was circumcised. The median lifetime number of female sex partners was six (range, 0–400), and the median number of female sex partners the past 12 months was one (range, 0–30). HPV detection showed that 41.7% of the total population was positive for HPV.

In Table 1, the age-adjusted associations between the five sexual behavior variables and odds of HPV infection are shown. Overall, older age at first sexual intercourse was associated with reduced odds of HPV (OR = 0.4; 95% CI: 0.3–0.6 for age ≥ 18 years vs. age ≤ 15 years at sexual debut). In contrast, increasing lifetime number of female sex partners (OR = 7.5; 95% CI: 5.6–10.0 for ≥ 11 sex partners vs. 1–2) and recent female sex partners (OR = 3.2; 95% CI: 2.5–4.1 for ≥ 4 sex partners vs. 1) and having had sexual intercourse with a woman less than 3 months prior to the examination (OR = 2.8; 95% CI: 2.1–3.7 for last sexual intercourse ≤ 3 months vs. ≥ 4 months ago) increased the odds of genital HPV infection. There was no difference in the odds of an HPV infection between men who reported to have used condoms in the past 12 months compared with men who had sex but did not use condoms.

Table 1.

Association between different sexual behavior variables and prevalent HPV infection among 2331 men from Denmark.

Risk factor	Total number of men	HPV positive, n (%)		OR^a	(95% CI)
Age at first sexual intercourse with a woman
≤15 years	916	455	(49.7)	1.0	(ref.)
16–17 years	839	361	(43.0)	0.7	(0.6–0.9)
≥18 years	423	147	(34.8)	0.4	(0.3–0.6)
Never had sex	153	8	(5.2)	0.1	(0.0–0.1)
Linear (per 1 year increase)*	1415	516	(36.5)	0.8	(0.8–0.9)
Lifetime number of female sex partners
0	153	8	(5.2)	0.2	(0.1–0.5)
1–2	432	83	(19.2)	1.0	(ref.)
3–5	541	185	(34.2)	2.1	(1.6–2.9)
6–10	541	253	(46.8)	3.4	(2.6–4.6)
≥11	664	442	(66.6)	7.5	(5.6–10.0)
Linear (per sex partner)*	2178	963	(44.2)	1.1	(1.0–1.1)
Number of female sex partners the past 12 months
0	267	27	(10.1)	0.2	(0.2–0.4)
1	1081	424	(39.2)	1.0	(ref.)
2–3	603	288	(47.8)	1.9	(1.5–2.3)
≥4	380	232	(61.1)	3.2	(2.5–4.1)
Linear (per sex partner)*	2064	944	(45,7)	1.2	(1.1–1.3)
Time since last sexual intercourse with a woman
≤3 months	1838	883	(48.0)	2.8	(2.1–3.7)
≥4 months	340	80	(23.5)	1.0	(ref.)
Never had sex	153	8	(5.2)	0.2	(0.1–0.4)
Condom use in the past 12 months
No	944	460	(48.7)	1.0	(ref.)
Yes	1123	479	(42.7)	0.9	(0.7–1.1)
No sex the past 12 months	111	24	(21.6)	0.3	(0.2–0.5)
Never had sex	153	8	(5.2)	0.1	(0.03–0.15)

OR: odds ratio; CI: confidence interval; HPV: human papillomavirus.

^aAdjusted for age as a continuous variable; *with an indicator variable for ever/never had sex.

The associations between HPV and smoking, alcohol use, and circumcision are shown in Table 2. In the age-adjusted model, current cigarette smoking was associated with increased odds of HPV (OR = 1.7; 95% CI: 1.4–2.0) compared with never smoking. Among current smokers, there was a dose–response pattern such that men smoking ≤ 10 cigarettes per day had increased odds of 1.5 (95% CI: 1.2–1.9) and men smoking 11–19 cigarettes per day had an odds ratio of 2.1 (95% CI: 1.5–2.9) both compared with noncurrent smokers. Men drinking more than six units of alcohol at the same occasion more than four times a month had slightly increased odds of HPV infection than men binge drinking 2–3 times per month (OR = 1.2; 95% CI: 0.9–1.4). After adjusting for sexual behavior, the association with current smoking attenuated (OR = 1.2; 95% CI: 1.0–1.4), and there was no clear pattern of a dose–response relationship, and no association with binge drinking was seen (Table 2). The odds of HPV was lower in circumcised men (OR = 0.7; 95% CI: 0.5–1.0) compared with uncircumcised men after taking into account age and sexual behavior.

Table 2.

Association between smoking, alcohol use, and circumcision and prevalent HPV infection among 2331 men from Denmark.

Risk factor	Total number of men			Age-adjusted model		Adjusted model
Risk factor	Total number of men	HPV positive, n (%)		OR^a	(95% CI)	OR^b	(95% CI)
Cigarette smoking
Never	1229	446	(36.3)	1.0	(ref.)	1.0	(ref.)
Former	198	89	(45.0)	1.1	(0.8–1.5)	0.9	(0.7–1.3)
Current	897	433	(48.3)	1.7	(1.4–2.0)	1.2	(1.0–1.4)
Cigarettes per day
Never and former	1427	535	(37.5)	1.0	(ref.)	1.0	(ref.)
≤10	421	190	(45.1)	1.5	(1.2–1.9)	1.2	(0.9–1.5)
11–19	180	96	(53.3)	2.1	(1.5–2.9)	1.4	(1.0–2.0)
≥20	252	126	(50.0)	1.7	(1.3–2.2)	1.0	(0.8–1.4)
Monthly binge drinking^c
≤1 time	611	285	(46.6)	1.0	(0.8–1.2)	1.1	(0.8–1.3)
2–3 times	1026	407	(39.7)	1.0	(ref.)	1.0	(ref.)
≥4 times	660	272	(41.2)	1.2	(0.9–1.4)	1.0	(0.8–1.3)
Circumcision
No	2206	927	(42.0)	1.0	(ref.)	1.0	(ref.)
Yes	125	44	(35.2)	0.8	(0.5–1.1)	0.7	(0.5–1.0)

OR: odds ratio; CI: confidence interval; HPV: human papillomavirus.

The number of men does not always add up to total due to missing values (smoking status (n = 7); binge drinking (n = 34), cigarettes per day (n = 44).

^aAdjusted for age as a continuous variable.

^bAdjusted for age, lifetime number of female sex partners and age at first sexual intercourse with a woman as continuous variables, and time since last sexual intercourse as a categorical variable.

^cMore than six units of alcohol at the same occasion.

In the analysis looking at the association between number of lifetime and recent partners, respectively, and HPV among circumcised and uncircumcised men, increasing number of partners was associated with increasing odds of HPV, whereas there seemed to be no association among circumcised men (Figure 1). Among uncircumcised men, the odds of HPV increased with increasing number of recent female sex partners after adjusting for sexual behavior (OR = 2.8; 95% CI: 2.1–3.7 for ≥ 4 female sex partners vs. 1 partner in the past 12 months) (Figure 1(a)). In contrast, the odds was 0.9 (95% CI: 0.3–2.4) for circumcised men having had more than four female sex partners the past 12 months versus one sex partner. The odds per partner was also higher and significantly increased for uncircumcised in contrast to circumcised (OR_uncircum 1.17, 95% CI: 1.12–1.24; OR_circum 1.07, 95% CI: 0.95–1.21 (data not shown)). Looking at the odds for HPV infection in relation to number of lifetime female sex partners, we observed the same pattern (Figure 1(b)). Comparing men having had more than 11 lifetime female sex partners with 1–2 partners showed that the odds of an HPV infection differed greatly between the two strata (uncircumcised men with ≥ 11 lifetime partners OR, 7.6; 95% CI, 5.3–10.9 vs. OR, 1.1; 95% CI, 0.3–3.7 in circumcised men). Again, considering the odds per partner, it was higher and significantly increased for uncircumcised individuals (OR_uncircum 1.06, 95% CI: 1.05–1.07) but not for circumcised (OR_circum 1.01, 95% CI: 0.98–1.03 (data not shown)).

Figure 1.

Adjusted odds ratios* of infection with any human papillomavirus type by circumcision status among 2331 men from Denmark: (a) according to number of female sex partners the past 12 months and (b) according to lifetime number of female sex partners. * Adjusted for age and age at first sexual intercourse with a woman as continuous variables and time since last sexual intercourse as a categorical variable.

Discussion

In this cross-sectional study examining factors associated with HPV infection among men from Denmark, we find that several sexual behavior factors are independent and important risk determinants that should be considered when examining other risk factors for HPV. Circumcised men had lower risk of HPV infection than did uncircumcised men, and our results suggest that circumcised men are less susceptible to the consequences of sexual risk behavior than uncircumcised men. However, due to a limited number of circumcised men in our study, this finding should to be interpreted with caution. We also find that current smoking is associated with prevalent HPV infection, however, with a less clear dose–response relationship after adjustment for sexual behavior. In contrast, we did not observe an association between alcohol use and HPV infection.

The association between sexual behavior and genital HPV is indisputable, and hence, it is crucial to take sexual behavior into account as confounders when examining other risk factors for genital HPV among men. Nevertheless, there is no consensus on how to adjust for sexual behavior. Based on the literature, we selected five sexual behavior variables, which have previously shown to be strongly associated with genital HPV infection and included them in our analyses.¹⁷ We mutually adjusted these sexual behavior variables to identify the variables of the most importance in our setting. We found that lifetime number of sex partners was a strong risk determinant and statistically significant after adjustment, which is in keeping with results from other investigators.^10-14,16 In addition, we found that time since last intercourse was a strong risk determinant in the mutually adjusted analysis, also concurring with some previously published results.¹¹ Last, we found that increasing age at sexual debut was significantly associated with lower risk of HPV after adjustment for the other sexual behavior variables. Increasing risk for HPV detection among men who were young at first sexual intercourse has also been reported previously by some,^{11,12,14,16,33} but not all studies.¹⁰ In contrast, condom use in the last 12 months and the number of female sex partners in the last 12 months were no longer significantly associated with genital HPV infection after adjustment for the other sexual variables. As the participants were quite young, there could potentially be a substantial overlap between lifetime partners and partners in the last 12 months. This should be kept in mind when considering other studies with a different age distribution.

In this study, we found that current smoking is associated with a slightly increased prevalence of HPV infection compared with never smokers also after adjusting for sexual behavior. However, results related to a potential dose–response relationship (cigarettes smoked per day) were not entirely convincing after taking sexual habits into account. Current tobacco use has previously been associated with an increased genital HPV prevalence among women,³⁴ and among men, an association between current smoking and increased risk of any, HR, and multiple HPV infections has also been demonstrated.^26,28 Previously, current smoking has also been associated with a higher probability of acquisition and persistence of genital HPV infection among men.^11,14,25,27 Nevertheless, the biological role of smoking on genital HPV infection among men is uncertain, and it is unclear if the higher HPV prevalence among current smokers is due to the increased susceptibility to or longer persistence of an HPV infection. It has been suggested that smoking can impair the immune response, thereby making it less competent to both new and persistent infections.^{28,31,34–36} In addition, it has been proposed that smoking may act as a proxy measure of sexual behavior.³¹ Even though our results showed that after thorough adjustment for sexual behavior, smoking was still associated with an increased risk of being HPV positive, the possibility of residual confounding cannot entirely be excluded.

In the age-adjusted analyses, binge drinking more than four times a month was associated with a slightly increased risk of HPV infection. However, after adjusting for sexual behavior, the association was no longer apparent. A limited number of studies have assessed the role of alcohol intake in relation to HPV prevalence. Some studies among men found that risk of HPV increased with increasing alcohol intake even after adjusting for sexual behavior, whereas other studies among women did not observe any association.^25,29,30 Our results mostly support the notion that the association between HPV and binge drinking is confounded by sexual behavior.

Overall, we observed a lower risk of prevalent HPV infection in circumcised men compared with uncircumcised men in line with others.^10,11,37 In Denmark, circumcision is most often performed for health reasons, primarily phimosis. Circumcision for cultural reasons constitutes a smaller proportion. A previous study has demonstrated that when sampling from multiple penile sites, the strength of an association between HPV and circumcision decreased with increasing distance from the urethra/coronal sulcus.²⁰ It was found that circumcision decreased the risk of HPV infection of the urethra and coronal sulcus/glans but was only marginally associated with a decreased risk at the penile shaft. As circumcision implies surgical removal of the foreskin, it is conceivable that protection against HPV infection is restricted to the glans area of the penis and has limited or no protection against HPV infection of the shaft or scrotum. We did not have information on site-specific HPV prevalence at the different sampling sites of the penis and consequently could not generate separate risk estimates according to anatomical sampling site.

Interestingly, we did not find that increasing number of female sex partners was associated with increased HPV detection among circumcised men as opposed to uncircumcised men. In line with this finding, a recent study reported that the risk of HPV infection did not increase with increasing number of sex partners among Tanzanian men where the majority of men are circumcised (88%).²³ This concurs with the suggestion made by some investigators that circumcision might protect men with higher risk behavior against HPV infection,^20,37 possibly due to circumcision changing susceptibility to HPV. It has previously been suggested that circumcision offers some kind of protection against HPV because the epithelium of the glans is cornified in a circumcised penis, making it less susceptible to entry of the virus.^21,37,38 This may also be supported by the abovementioned suggestion that the glans and corona are the anatomical sites of the penis where the protective effect of circumcision is the greatest.^14,20,22

Our study has strengths and limitations that should be considered. It is one of the largest European studies investigating risk factors for genital HPV among men representing the general population which increases the generalizability of our results. When the study population was recruited, HPV vaccination was not available for boys and men, and thus, our results relate to a population of unvaccinated men. Finally, the large sample size enabled the thorough adjustment for risk factors associated with sexual behavior underlining the robustness of our results. It is a limitation that only 5.4% of the men were circumcised, and despite our large study population, some analyses are based on a limited number of circumcised men and should be interpreted cautiously.

In summary, our findings make an important contribution to the understanding of the natural history of genital HPV among men. Our results indicated that circumcision is associated with a reduced risk of HPV and that there may be some biological differences in the susceptibility of HPV infection between circumcised and uncircumcised men. Additional studies should clarify the potential benefits of circumcision concerning genital HPV infection and HPV-related diseases. We showed that among men representing the general population in Denmark, current smoking seems to slightly increase the risk of HPV infection after adjustment for differences in sexual behavior, whereas no effect of alcohol use was evident. Establishing risk factors for HPV and understanding the natural history of the virus improve the possibility to make future recommendations and potential prevention strategies for this common sexually transmitted infection.

Summary

A population-based study among men from Denmark found that circumcision reduces the risk of genital HPV infection and seems to modify the effect of sexual partners. Smoking slightly increases the risk.

Footnotes

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Susanne Krüger Kjær has received lecture fees, advisory board fees, and unrestricted research grants through her institution from Merck and Sanofi Pasteur MSD. Thomas Iftner has received lecture fees and research grants through his institution from Hologic GmbH and Roche Diagnostics GmbH. Julie Buchholt Hebnes, Christian Munk, Kirsten Frederiksen, and Hans Ole Jørgensen all have nothing to disclose.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Merck.

ORCID iDs

Christian Munk

Susanne K Kjaer

References

Chesson

Dunne

Hariri

, et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014; 41(11): 660–664.

Svahn

Munk

von Buchwald

, et al. Burden and incidence of human papillomavirus-associated cancers and precancerous lesions in Denmark. Scand J Public Health 2016; 44(6): 551–559.

Moscicki

Schiffman

Burchell

, et al. Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 2012; 30(Suppl 5): F24–F33.

Nyitray

Iannacone

. The epidemiology of human papillomaviruses. Hum Papillomavirus 2014; 45: 75–91.

Bosch

de Sanjosé

. The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers 2007; 23(4):213–227.

IARC Working Group. Human papillomaviruses. IARC Monogr Eval carcinogenic risks humans 2007; 90: 1–636.

Moscicki

A-B

Palefsky

. Human papillomavirus in men. J Lower Genital Tract Dis 2011; 15(3): 231–234.

Smith

Melendy

Rana

, et al. Age-specific prevalence of infection with human papillomavirus in females: a global review. J Adolesc Health 2008; 43(4 SupplS5–25): Se1–Se41.

Deshmukh

Tanner

Luetke

, et al. Prevalence and risk of penile human papillomavirus infection: evidence from the national health and nutrition examination survey 2013-2014. Clin Infect Dis 2017; 64(10): 1360–1366.

10.

Svare

Kjaer

Worm

, 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 Infections 2002; 78(3): 215–218.

11.

Giuliano

Lazcano

Villa

, et al. Circumcision and sexual behavior: factors independently associated with human papillomavirus detection among men in the HIM study. Int J Cancer 2009; 124(6): 1251–1257.

12.

Johnson

Mercer

Beddows

, et al. Epidemiology of, and behavioural risk factors for, sexually transmitted human papillomavirus infection in men and women in Britain. Sex Transm Infections 2012; 88(3): 212–217.

13.

Vardas

Giuliano

Goldstone

, et al. External genital human papillomavirus prevalence and associated factors among heterosexual men on 5 continents. J Infect Dis 2011; 203(1): 58–65.

14.

Nielson

Harris

Dunne

, et al. Risk factors for anogenital human papillomavirus infection in men. The J Infect Dis 2007; 196(8): 1137–1145.

15.

Partridge

Hughes

Feng

, et al. Genital human papillomavirus infection in men: incidence and risk factors in a cohort of university students. The J Infect Dis 2007; 196(8): 1128–1136.

16.

Shin

Franceschi

Vaccarella

, et al. Prevalence and determinants of genital infection with papillomavirus, in female and male university students in Busan, South Korea. The J Infect Dis 2004; 190(3): 468–476.

17.

Tota

Chevarie-Davis

Richardson

, et al. Epidemiology and burden of HPV infection and related diseases: implications for prevention strategies. Prev Med 2011; 53(Suppl 1): S12–S21.

18.

Larke

Thomas

Dos Santos Silva

, et al. Male circumcision and human papillomavirus infection in men: a systematic review and meta-analysis. The J Infect Dis 2011; 204(9): 1375–1390.

19.

Albero

Castellsagué

Giuliano

, et al. Male circumcision and genital human papillomavirus. Sex Transm Dis 2012; 39(2): 104–113.

20.

Nielson

Schiaffino

Dunne

, et al. Associations between male anogenital human papillomavirus infection and circumcision by anatomic site sampled and lifetime number of female sex partners. J Infect Dis 2009; 199(1): 7–13.

21.

Zhu

Jia

Dai

, et al. Relationship between circumcision and human papillomavirus infection: a systematic review and meta-analysis. Asian J Androl 2017; 19(1): 125–131.

22.

Albero

Villa

Lazcano-Ponce

, et al. Male circumcision and prevalence of genital human papillomavirus infection in men: a multinational study. BMC Infect Dis 2013; 13: 18.

23.

Olesen

Mwaiselage

Iftner

, et al. Risk factors for genital human papillomavirus among men in Tanzania. J Med Virol 2017; 89(2): 345–351.

24.

Lopez-Diez

Perez

Carballo

, et al. Lifestyle factors and oncogenic papillomavirus infection in a high-risk male population. PLoS One 2017; 12(9): e0184492.

25.

Nielsen

Munk

Jørgensen

, et al. Multiple-type human papillomavirus infection in younger uncircumcised men. Int J STD AIDS 2013; 24(2): 128–133.

26.

Nielson

Harris

Flores

, et al. Multiple-type human papillomavirus infection in male anogenital sites: prevalence and associated factors. Cancer Epidemiol Biomarkers Prev 2009; 18(4): 1077–1083.

27.

Kjaer

Munk

Winther

, 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(6): 1528–1533.

28.

Schabath

Villa

Lazcano-Ponce

, et al. Smoking and human papillomavirus (HPV) infection in the HPV in Men (HIM) study. Cancer Epidemiol Biomarkers Prev 2012; 21(1): 102–110.

29.

Schabath

Thompson

Egan

, et al. Alcohol consumption and prevalence of human papillomavirus (HPV) infection among US men in the HPV in Men (HIM) study. Sex Transm Infect 2014; 91(1): 61–67.

30.

Sikström

Hellberg

Nilsson

, et al. Smoking, alcohol, sexual behaviour and drug use in women with cervical human papillomavirus infection. Arch Gynecol Obstet 1995; 256(3): 131–137.

31.

Burchell

Winer

de Sanjosé

, et al. Chapter 6: epidemiology and transmission dynamics of genital HPV infection. Vaccine 2006; 24(Suppl 3): S52–S61.

32.

Hebnes

Munk

Nøhr

, et al. Human papillomavirus infection among 2460 men in denmark. Sex Transm Dis 2015; 42(8): 463–467.

33.

Parada

Morales

Giuliano

, et al. Prevalence, concordance and determinants of human papillomavirus infection among heterosexual partners in a rural region in central Mexico. BMC Infect Dis 2010; 10: 223.

34.

Vaccarella

Herrero

Snijders

PJF

, et al. Smoking and human papillomavirus infection: pooled analysis of the international agency for research on cancer HPV prevalence surveys. Int J Epidemiol 2008; 37(3): 536–546.

35.

Schabath

Villa

Lin

H-Y

, et al. A prospective analysis of smoking and human papillomavirus infection among men in the HPV in Men Study. Int J Cancer 2014; 134(10): 2448–2457.

36.

Giuliano

Sedjo

Roe

, et al. Clearance of oncogenic human papillomavirus (HPV) infection: effect of smoking (United States). Cancer Causes and Control 2002; 13(9): 839–846.

37.

Castellsague

Bosch

Muñoz

, et al. Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. New Engl J Med 2002; 346(15): 1105–1112.

38.

Hernandez

Wilkens

Zhu

, et al. Circumcision and human papillomavirus infection in men: a site‐specific comparison. The J Infect Dis 2008; 197(6): 787–794.