Downloaded from sti.bmj.com on September 25, 2013 - Published by group.bmj.com Self-collection of genital human papillomavirus specimens in heterosexual men G S Ogilvie, D L Taylor, M Achen, et al. Sex Transm Infect 2009 85: 221-225 originally published online December 9, 2008 doi: 10.1136/sti.2008.033068 Updated information and services can be found at: http://sti.bmj.com/content/85/3/221.full.html These include: Data Supplement "web only appendix" http://sti.bmj.com/content/suppl/2009/01/07/sti.2008.033068.DC1.html References This article cites 16 articles, 10 of which can be accessed free at: http://sti.bmj.com/content/85/3/221.full.html#ref-list-1 Article cited in: http://sti.bmj.com/content/85/3/221.full.html#related-urls Email alerting service Topic Collections Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article. Articles on similar topics can be found in the following collections Human papilloma virus (HPV) (7 articles) Notes To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/ Downloaded from sti.bmj.com on September 25, 2013 - Published by group.bmj.com Health Services Research Self-collection of genital human papillomavirus specimens in heterosexual men G S Ogilvie,1,2 D L Taylor,1,2 M Achen,2 D Cook,2 M Krajden1,2 1 University of British Columbia, Vancouver, Canada; 2 British Columbia Centre for Disease Control, Vancouver, Canada Correspondence to: Gina Ogilvie, Associate Director, Division of STI/HIV Prevention and Control, British Columbia, Centre for Disease Control, Assistant Professor, Department of Family Practice, University of British Columbia, 655 West 12th Avenue, Vancouver, British Columbia, V5Z 4R4, Canada; gina.ogilvie@bccdc.ca Accepted 14 November 2008 Published Online First 9 December 2008 ABSTRACT Background: We assessed the accuracy of selfcollected human papillomavirus (HPV) specimens in men compared with clinician-collected specimens from men in British Columbia and determined the prevalence of HPV subtypes at different male genital sites. Methods: Heterosexual men were recruited at the Provincial Sexually Transmitted Infection (STI) Clinic in Vancouver, Canada. Participants were randomly assigned to conduct self-collection or clinician-collected specimens first. Clinicians obtained specimens using emery paper followed by saline-moistened Dacron swab from three genitourinary sites: glans penis/foreskin, penile shaft (ventral and dorsal surfaces) and scrotum. Participants received written instructions and took specimens from one of the three sites using the same technique as clinicians. HPV testing was performed with the Roche Amplicor HPV test and samples found to be reactive were tested with the Roche Linear Array HPV typing assay to establish the HPV genotype(s) in the sample. Results: Overall prevalence of any HPV genotype from any site was 69.8% in clinician-collected specimens and 55.3% in self-collected specimens. Order of collection (clinician vs self-collected) did not impact on the prevalence of HPV in the specimens. The k scores for agreement between clinician-collected and self-collected specimens ranged from fair to excellent. Overall, there was better agreement between self-collected and clinician-collected specimens for HPV-18 (range: k = 0.88 to 0.92) than for HPV-16 (range: k = 036 to 0.62). Conclusion: HPV is a prevalent genital tract infection in men. Site-specific agreement for specific HPV genotypes between clinician-collected and self-collected specimens varied broadly and neither clinicians nor patients routinely obtained samples with consistently higher or lower prevalence at specific genital sites, indicating there are continued opportunities to improve techniques for clinician-collected and self-collected male specimens for HPV. Human papillomavirus (HPV) is transmitted by skin to skin and sexual contact and certain genotypes are now understood to be the cause of cervical cancer.1 Significant work has been done on understanding the prevalence and natural history of HPV in women2 and increasingly with men who have sex with men (MSM) populations.3 However, relatively little is known about HPV infections in heterosexual men.4 5 One of main issues for studying HPV in heterosexual men remains the challenge of specimen collection.6–8 Data are evolving regarding which genital sites in men should be tested for HPV and how specimens should be collected in order to determine the epidemiology of HPV genital infections for the men themselves and Sex Transm Infect 2009;85:221–225. doi:10.1136/sti.2008.033068 for transmission to sexual partners. Because HPV is a virus that infects the epithelium, studies that have been conducted on HPV in heterosexual men rely on epidermal debriding followed by specimen collection by a saline-moistened Dacron swab.9 However, because men are often reluctant to participate in testing for sexually transmitted infections (STIs), and may find epidermal debriding unappealing, self-sampling presents an important option to increase uptake of testing both in clinical and research settings. In this study, we assessed the accuracy of self-collected HPV specimens in men compared with clinician-collected specimens and determined the prevalence of HPV subtypes at different male genital sites from heterosexual men in British Columbia. METHODS Men who reported never having sex with another man and who presented for STI screening at the Provincial STI Clinic at the British Columbia Centre for Disease Control in Vancouver, Canada, were invited to participate in this study. After providing informed consent, participants were administered a structured questionnaire by an experienced, trained healthcare provider to assess sexual history, risk factors for STIs, sociodemographic variables and self-reported history of STIs, including human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoea and herpes simplex virus. Study participants received honoraria of $CAN15. Specimen collection All participants self-collected their specimens and underwent clinician-collected specimen testing. Participants were randomly assigned to conduct self-collection or clinician-collected specimens first and to obtain their self-collected specimen from one of three sites. Clinical staff obtained specimen staff obtained specimens using emery paper followed by a saline-moistened Dacron swab from three genitourinary sites: glans penis/foreskin, penile shaft (ventral and dorsal surfaces) and scrotum.9 Participants received written instructions and took specimens from one of the three sites using the same technique as clinicians. Laboratory analysis Both the emery paper and the swab from each sampling site were placed together into a sample transport tube containing 1 ml of specimen transport medium (Digene Corporation, Gaithersburg, Maryland, USA), which was stored at room temperature (18–30uC) for no more than 48 hours until delivered to the laboratory. HPV testing was performed with the Roche Amplicor HPV test 221 Health Services Research (Roche, Canada) following the manufacturer’s instructions. All samples found to be reactive with the Amplicor micro-well plate assay were subsequently tested with the Roche Linear Array HPV typing assay to establish the HPV genotype(s) in the sample. Both the Amplicor and Linear Array tests include a b-globin control to assess sample adequacy. Specimens testing negative for b-globin were considered to be inadequate and were not included in the analysis. Statistical analysis Demographic characteristics, sexual history and sexual practices from the study participants were determined. Rates of sample adequacy were compared between clinician-collected and selfcollected specimens. Prevalence of HPV overall and for different genotypes and at different genital sites was determined. Overall prevalence rates were compared between study participants where clinicians collected specimens first and participants collected specimens first using x2 statistics. Characteristics of men who were positive for any HPV and for HPV-16 or HPV-18 were compared with men who were negative for HPV-16 or HPV-18 using x2 statistics for categorical variables and independent t test for continuous variables. Variables that achieve p,0.05 were offered for inclusion in a multivariable model to achieve a best-fit model. Backwards logistic regression was conducted to calculate adjusted odds ratios (AORs) to identify the factors that were predictive of overall HPV status and HPV-16 or HPV-18 status. Concordance in genotypespecific HPV detection between self-collected and cliniciancollected specimens at different sites was determined using Cohen’s k statistic. Analysis was performed using SPSS 14.0 for Windows. RESULTS Over a 10-month period, 297 men were recruited and, overall, 88% (n = 262) of the specimens were deemed adequate as confirmed by detection of b-globin in both the cliniciancollected and the self-collected specimens and were included in the analysis. There was no difference in rates of specimen adequacy between clinician-collected and self-collected specimens (86.9% vs 89.5%; p.0.05). Study participants ranged in age from 16–69 years (median 29 years). Median age of first intercourse was 17 years, with a median of 15 lifetime sexual partners and 2 in the past 6 months. Just over a quarter of participants reported condom use all the time, but over 50% reported condom use during their last sexual encounter. Over 50% reported a history of some type of STI at some point in their life (table 1). Overall prevalence of any HPV genotype from any site was 69.8% in clinician-collected specimens and 55.3% in selfcollected specimens (table 2). Order of collection (clinician vs self-collected) did not impact on the prevalence of HPV in the specimens (65.9% vs 73.5%; p = 0.18). Prevalence of vaccine preventable genotypes (HPV 6, 11, 16 or 18) and high risk types (HPV 16, 18) in clinician-collected specimens was 35.1% and 24.0%, respectively, and 43.1% had evidence of infection with more than one HPV subtype at any site. Overall prevalence of HPV-16 was 18.7% and 8.4% for HPV-18. There was no consistent pattern in overall detection as prevalence at some sites was higher with clinician-collected specimens (penile shaft) and others higher with the self-collected specimens (glans/ foreskin and scrotum). In bivariate analyses, individuals who were HPV positive were significantly more likely to have had their first sexual encounter at a younger age, have a higher 222 Table 1 Characteristics of the study participants (n = 262) Characteristic Age (y) (n = 260) Median Age (y) at first intercourse (n = 259) Median Lifetime sexual partners (n = 257) Median Number of sexual partners in past 6 months (n = 258) Median Circumcision status Circumcised Non-circumcised Gender of sexual partners Only female sexual partners Only male sexual partners Both male and female sexual partners Frequency of vaginal intercourse in past month 0 1–5 times 6–30 times .30 times Missing Condom use during past 6 months with all partners Never Sometimes Always Missing Condom use at last sexual encounter No Yes Missing Condom use with steady partner during past 6 months Never Sometimes Always Not applicable Condom use with extramarital partners in past 6 months Never Sometimes Always Not applicable Missing Marital status Single/separated/divorced Married/common-law Missing Ethnicity White/Caucasian Asian Hispanic South Asian First nations Other Employment Full-time Part-time Disabled, unemployed, social assistance Annual income ,$50K >$50K Missing History of sexually transmitted infection (STI) No history of STI History of STI Mean Range 29.0 16–69 17.0 10–29 15.0 1–200 2.0 n 0–20 % 132 130 50.4 49.6 258 1 3 98.5 0.3 1.1 65 99 91 6 1 24.8 37.8 34.7 2.3 0.4 49 133 70 10 18.7 50.8 26.7 3.8 125 136 1 47.7 51.9 0.4 54 80 39 89 20.6 30.5 14.9 34.0 16 51 60 131 4 6.1 19.5 22.9 50.0 1.5 220 40 2 84.0 15.3 0.8 198 26 6 5 3 22 75.6 9.9 2.3 1.9 1.1 9.1 174 31 57 66.4 11.8 21.8 160 77 25 61.1 29.4 9.5 125 137 47.7 52.3 Sex Transm Infect 2009;85:221–225. doi:10.1136/sti.2008.033068 Health Services Research number of lifetime sexual partners, have a higher number of sexual partners in the past 6 months, report never using condoms and self-report having had a STI. In multivariable modelling, individuals who were HPV positive were significantly more likely to have had their first sexual encounter at a younger age, have a higher number of lifetime sexual partners and were more likely to self-report having had a STI. Individuals who were positive for either HPV-16 or HPV-18 were significantly less likely to report that they always used a condom with sexual partners (table 3). In multivariable modelling, never having used a condom with partner in the last 6 months was significantly associated with HPV-16 or HPV18 infection compared with those who always used a condom. Correlation of type-specific HPV detection at the three different genital sites was evaluated between the clinician and self-collected specimens. The k scores for agreement between clinician-collected and self-collected specimens ranged from fair to excellent (table 4). The best agreement was found for HPV-18 in the shaft (k = 0.92) and the poorest agreement was found for HPV-16 for the glans/foreskin (k = 0.36). Overall, there was better agreement between clinician-collected and self-collected specimens for HPV-18 (k = 0.88 t 0.92) than for HPV-16 (k = 036 to 0.62). DISCUSSION In this study of heterosexual men recruited at a provincial STI clinic, over 60% were HPV positive and almost a third were positive for HPV types contained in the quadrivalent HPV vaccine. In the self-collected specimens, where participants sampled only one site, overall prevalence was 55.3%. Using the emery paper and swab system, men were able to self-collect specimens from the glans/foreskin, penile shaft and scrotum for HPV and were able to provide adequate specimens based on b-globin detection. Order of specimen collection (clinician or self) did not appear to impact on the detection of HPV, indicating that self-collected specimen methods are not influenced by either viewing the nurse collect the specimen or by nurses debriding the epithelium prior to patient collection. However, site-specific agreement for specific HPV subtypes between clinicians and patients varied broadly and neither clinicians nor patients routinely obtained samples with consistently higher or lower prevalence at specific genital sites, indicating there are continued opportunities to improve techniques for male self-collected specimens for HPV, including overall acceptability of the method and development of improved sampling tools. The overall prevalence for any HPV found in this study (69.8%) was higher than rates found in other studies where both younger men were included10 and in studies where men aged between 18 and 44 years were included.11 In studies that included glans/foreskin, penile shaft and scrotum, using similar specimen collection techniques, prevalence for any HPV infection ranged from 35%,9 to just over 40%12 to almost 60%.6 In this study, only 20% of participants were under the age of 25 years compared with 49.9% in Nielson’s study.7 In another study on HPV prevalence in men, where overall prevalence was 33.8%, the mean age of participants was 20.3 years compared with 32.0 years in this current study.13 Thus, given recent findings by Partridge, which showed the cumulative incidence of new HPV infections in men at 62.4%,14 our prevalence findings of 69.8% are not unexpected. We recruited men at the provincial STI clinic who were older than those recruited in other studies and who reported a high number of lifetime partners; thus, increasing their exposure to HPV than other studies of university students, the military or community based samples. The reason for the difference in the level of agreement between self-collected and clinician-collected HPV genotypes is unclear and warrants further examination. Certainly, it has been established that there is variation in the duration of infection with different HPV genotypes in women as well as differing characteristics in terms of clearance rates for prevalent versus incident infections.15 Perhaps the level of integration into the epithelium or viral load in prevalent compared with incident infections impacted on the level of agreement for HPV-16. Further research on the characteristics and natural history of type-specific HPV infection in men will likely offer important insight into the potential reason for the variation in agreement between HPV genotypes. Genital HPV infection is common and infects the genital region broadly. Similar to the studies by Nielson7 and Partridge,14 HPV prevalence for any type was highest on the penile shaft, then for the glans/foreskin and lowest in the scrotum, although this difference did not achieve statistical Table 2 Overall and type-specific prevalence in clinician-collected and self-collected human papillomavirus (HPV) specimens Overall prevalence (n = 262) HPV-16 HPV-18 Glans penis/foreskin (n = 262) Overall HPV-16 HPV-18 Penile shaft (n = 262) Overall HPV-16 HPV-18 Scrotum (n = 262) Overall HPV-16 HPV-18 Clinician collected n % (95% CI) Patient collected n % (95% CI) 183 49 22 69.8 (64.2 to 75.4) 18.7 (14.0 to 23.4) 8.4 (5.0 to 11.8) 145 30 16 55.3 (49.3 to 61.3) 11.5 (7.6 to 15.3) 6.1 (3.2 to 8.9) 137 33 14 52.3 (46.3 to 58.3) 12.6 (8.6 to 16.6) 5.3 (2.5 to 8.0) 52 8 5 58.4 (52.4 to 64.3) 9.0 (5.5 to 12.4) 5.6 (2.8 to 8.4) 159 36 20 60.7 (54.8, 66.6) 13.7 (9.8,17.8) 7.6 (4.4 to 10.8) 47 10 6 51.6 (45.5, 57.7) 11.0 (7.2 to 14.8) 6.6 (3.6 to 9.6) 129 28 12 49.2 (43.1 to 55.2) 10.7 (6.9 to 14.4) 4.6 (2.0 to 7.1) 46 12 5 56.1 (50.1, 62.1) 14.6 (10.3, 18.9) 6.1 (3.2 to 9.0) Sex Transm Infect 2009;85:221–225. doi:10.1136/sti.2008.033068 223 Health Services Research Table 3 Characteristics of study participants by human papillomavirus (HPV) status Characteristic Age, y (mean) Negative Positive Age at first intercourse (mean) Negative Positive Lifetime sexual partners (mean) Negative Positive Number of sexual partners in past 6 months (mean) Negative Positive Circumcision status Circumcised Non-circumcised Frequency of vaginal intercourse in past month 0 1–5 times 6–30 times .30 times Condom use during past 6 months with all partners Never Sometimes Always Missing Condom use at last sexual encounter No Yes Missing Condom use with steady partner during past 6 months Never Sometimes Always Not applicable Marital status Single/separated/divorced Married/common-law Ethnicity White/Caucasian Asian Hispanic South Asian First nations Other Employment Full-time Part-time Disabled, unemployed, social assistance Annual income ,$50K >$50K History of STI (CT, NG, HSV) No history of STI History of STI Overall HPV status (n = 262) p Value HPV-16/18 status (n = 262) p Value 30.9 32.5 0.24 32.2 31.2 0.46 18.5 16.8 0.00 17.4 17.2 0.61 14.3 40.2 0.01 30.4 38.7 0.45 0.04 2.6 3.4 HPV-16 or 1HPV-8 positive (n = 262) 0.07 94 (71.2) 89 (68.5) 0.63 38 (28.8) 25 (19.2) 0.07 41 69 67 5 (63.1) (69.7) (73.6) (83.3) 0.47 13 23 24 2 (20.0) (23.2) (26.4) (33.3) 0.76 39 (79.6) 99 (74.4) 42 (60.0) 0.04 11 (22.4) 41 (30.8) 10 (14.3) 0.03 93 (74.4) 90 (66.2) 0.11 30 (24.0) 33 (24.2) 0.85 43 55 26 59 (79.6) (68.8) (66.7) (66.3) 0.36 11 17 11 24 (20.4) (21.3) (28.2) (27.0) 0.68 156 (70.9) 25 (62.5) 0.29 56 (25.5) 7 (17.5) 0.28 140 13 5 1 2 (70.7) (50.0) (83.3) (20.0) (66.7) 0.07 49 4 1 0 0 (24.7) (15.4) (16.7) (0.0) (0.0) 0.29 125 (71.8) 24 (77.4) 34 (59.6) 0.14 42 (24.1) 7 (22.6) 14 (24.6) 0.98 113 (70.6) 50 (64.9) 0.38 37 (22.1) 17 (21.1) 0.86 71 (56.8) 112 (81.8) 0.00 24 (19.2) 39 (28.5) 0.08 2.2 3.1 HPV positive (n = 262) CT, Chlamydia trachomatis; NG, Neisseria gonorrhoea; HSV, herpes simplex virus; STI, sexually transmitted infection. 224 Sex Transm Infect 2009;85:221–225. doi:10.1136/sti.2008.033068 Health Services Research Table 4 Type-specific agreement between clinician-collected and self-collected human papillomavirus (HPV) specimens by site* Glans/foreskin (n = 89) Shaft (n = 91) Scrotum (n = 82) HPV-16 HPV-18 0.36 (0.0 to 0.7) 0.55 (0.3, 0.8) 0.62 (0.3, 0.9) 0.90 (0.7 to 1.0) 0.92 (0.7, 1.0) 0.88 (0.6, 1.0) *Cohen’s k. Ethics approval: Ethics approval was received for this study from the University of British Columbia, Canada. Contributors: GSO conceived the study, designed the study, designed and conducted the analysis and prepared the first draft of the manuscript. GSO, DLT, MA, DC and MK implemented the study. All authors contributed to study design and data analysis and revised the manuscript. REFERENCES 1. 2. Key messages c c c Human papillomavirus (HPV) is a prevalent genital tract infection in men. Site-specific agreement for specific HPV genotypes between clinicians and patients varies broadly. There are continued opportunities to improve techniques for self-collected male specimens for HPV. 3. 4. 5. 6. 7. significance. Site-specific prevalence for HPV-16 overall, at the glans/foreskin, shaft and scrotum were 18.7%, 12.6%, 13.7% and 10.7%, respectively, in this study compared with 11.4%, 9.1%, 4.1% and 5.0% in Nielson’s study.7 This study indicates the high prevalence of vaccine-preventable HPV carriage in heterosexual men and, therefore, the possible benefit of the HPV vaccine for men to reduce the risk for HPV-associated penile carcinomas5 and to reduce HPV transmission to women. There is a clear need for continued study to establish the clinical efficacy of the HPV vaccine in heterosexual men and to consider the role of HPV vaccination in young men.16 Acknowledgements: The authors would like to acknowledge the guidance of Dr Philip Davies in the design of this study and Dr Jonathan Berkowitz in the statistical analysis of the data. We also are indebted to the enormous contributions of the clinical and clerical staff at the Provincial STI Clinic at the British Columbia Centre for Disease Control. 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