EDITORIAL COMMENTARY
Young Gay Men and the Quadrivalent Human Papillomavirus Vaccine—Much to Gain (and Lose) Ross D. Cranston Department of Medicine, University of Pittsburgh, Pennsylvania
(See the major article by Huachun et al on pages 642–51.)
Keywords.
Human papillomavirus (HPV); vaccine; gay men; quadrivalent; anogenital.
Received and accepted 4 November 2013; electronically published 21 November 2013. Correspondence: Ross D. Cranston, MB ChB, MD, FRCP, University of Pittsburgh, 3520 Fifth Ave, Keystone Bldg, Ste 510, Pittsburgh, PA 15213 ([email protected]). The Journal of Infectious Diseases 2014;209:635–8 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jit627
rates of anogenital HPV infection and also HPV-associated malignancy, particularly HPV 16–associated anal cancer [6, 7]. HPV vaccination has been shown to be safe and effective in preventing the acquisition of anogenital HPV infection and the development of dysplasia [8–10]. The challenge ahead is to ensure that vaccinations are available to those at risk in a manner that optimizes their efficacy. There are 2 licensed HPV vaccines: a bivalent vaccine directed against HPV 16 and 18 (Cervarix, GlaxoSmithKline, London, UK) licensed for females aged 9–25 years, and a quadrivalent HPV vaccine (qHPV) directed against HPV 6, 11, 16, and 18 (Gardasil, Merck, Whitehouse Station, NJ) licensed for females and males ages 9–26 years. Both vaccines’ indications include prevention of warts and female genital dysplasia/cancer, with qHPV also indicated for anal dysplasia/ cancer. These prophylactic vaccines induce high-titer HPV antibody levels with good efficacy and an excellent safety profile [11, 12]. In this issue of The Journal of Infectious Diseases, Zou and colleagues examined acquisition of anogenital HPV in a population of MSM. They enrolled men between the ages of 16 and 20 years who self-identified as same-sex attracted. Thus, they were able to assess incident HPV infection in MSM with limited sexual experience who might benefit from HPV vaccination if they had the
same access to HPV vaccines as adolescent girls. Following recruitment from a variety of venues, participants were seen for assessments at baseline and then at 3, 6, and 12 months. At each visit, participants had a clinical exam, completed a sexual experience questionnaire, had a blood sample drawn for HPV serology, and swabs taken from penile, perianal, and intra-anal sites. An oral saline gargle was also collected. All these samples were tested for HPV DNA by polymerase chain reaction. Additionally, participants were tested for gonorrhea, chlamydia, syphilis, and HIV at each visit. At the 12-month visit, participants were offered the qHPV. The median age of study participants was 19 years and the majority had engaged in both receptive and insertive anal intercourse. Thirty-nine percent of participants had at least 1 of 37 HPV types tested for at the anatomical sites sampled, and 23% had at least 1 qHPV type. Overall, at least 1 high-risk HPV was detected in 31% of participants. In participants with 0 to ≥4 receptive and insertive anal-sex partners, the respective proportion of anal (P < .001) and penile (P < .014) HPV increased significantly. This trend also reached significance for detection of anal HPV 16. In another study conducted in a slightly older age group of 94 MSM with a mean age of 21 years, 70% had any of the 37 HPV types
EDITORIAL COMMENTARY
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JID 2014:209 (1 March)
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635
Downloaded from http://jid.oxfordjournals.org/ at Northern Kentucky University on July 4, 2015
Human papillomavirus (HPV) is the world’s most common viral sexually transmitted infection [1, 2]. Approximately 40 HPV types infect anogenital squamous epithelium and can be broadly divided into low-risk (eg, HPV 6, 11) and high-risk (eg, HPV 16, 18) phenotypes based on their historical association with cervical cancer. This relationship also holds true for other anogenital (anal, vulvar, vaginal) and oropharyngeal malignancies. Although most HPV infections are asymptomatic, when symptoms do occur, they often reflect the presence of warts, dysplasia, or frank malignancy. Anogenital HPV infection is mostly transient in both sexes, with persistent high-risk HPV infection associated with the development of squamous-cell cancers [3, 4]. HPV prevalence data vary by gender, with men being more likely to have higher-level detection over a wider age range than women, whose prevalence decreases from a peak in their early 20s [3, 5] However, it is men who have sex with men (MSM) who have the highest
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HPV presence, and may contribute to the explanation of why 10% of participants with anal HPV reported no RAI. There was also a low/moderate correlation of DNA detection and serology that may also reflect a delay in developing a serological response. Newer testing platforms that detect HPV mRNA may be more predictive of established infection than the detection of HPV DNA alone [21]. In the absence of routine vaccination of school-age boys aged 12–13 years, individuals would have to actively seek vaccination from a health care provider based on their self-identification as MSM. In this study, participants were asked if they would be willing to identify as MSM in order to access HPV vaccination, and 85.5% agreed, although only 55.5% had previously disclosed their sexuality to their primary care physician. This is similar to data from the US National HIV Behavioral Surveillance System that indicated almost 90% of young MSM had used health care in the last 12 months, but only 61.3% disclosed their sexuality to the provider [22] Almost 20% of participants in the current study had experienced vaginal sex, suggesting that sexuality identity had not yet fully formed or that the individual’s sexuality was more fluid. In both cases, the individual may be exposed to HPV before seeking a vaccine specifically aimed at a MSM demographic. Cost-effective analyses of the widespread vaccination of boys have consistently shown that there is no benefit beyond that achieved by high rates of vaccine uptake in girls, and induction of herd immunity [23–25]. However, this will likely have little if any effect on HPV infection in MSM, leaving an unprotected demographic with the greatest risk of HPV infection and its complications. However, when MSM are considered in isolation, vaccination becomes cost effective based on the standard parameter of costing less than US$50 000 per qualityadjusted life-year [26]. However, in these models, the cost effectiveness wanes as age at vaccination, sexual partner number,
EDITORIAL COMMENTARY
and HPV prevalence increase. The licensure studies of qHPV in MSM are instructive, as they enrolled a broadly similar cohort of participants to the Zou et al study (ie, MSM aged 16–26 years who had ≤5 sex partners). Both the per protocol (with no serological or DNA evidence of HPV infection) and intent-to-treat analyses demonstrated efficacy for the prevention of qHPV types, as well as for the prevention of warts and both low- and high-grade anal dysplasia [9]. Thus, despite the HPV exposure in the Zou et al study, vaccination of individuals may be of benefit, albeit at a reduced rate compared to non-HPV–exposed individuals. This finding is particularly important when considering a focused MSM vaccine strategy where individuals self-identifying as MSM who request the qHPV would most likely have encountered HPV infection through prior sexual activity. The Zou et al study offered qHPV to all study participants at the 12-month visit, with an uptake rate of 96%. Whereas MSM have been shown to be more knowledgeable about HPV than heterosexual men, their self-perception of willingness to be vaccinated was only moderate in a meta-analysis of 29 studies [27, 28]. Rates of uptake of HPV vaccination are strongly correlated to the ease with which potential recipients can access vaccination. For females in Scotland and England where vaccination is free and offered to school-age girls, coverage is over 70% for completion of all 3 vaccinations [29, 30]. In the United States, coverage for girls critically depends upon venue of administration, with school-based systems achieving higher coverage than other strategies [31]. The Australian government has been extremely active in addressing HPV infection, with the National Immunization Program instituting a free vaccination program for Australian National girls aged 12–13 years in 2007, with catch-up vaccination possible up to age 26 years until 2009. In February 2013, this program was extended to boys aged 12–13 years, with catch-up vaccination possible up to
Downloaded from http://jid.oxfordjournals.org/ at Northern Kentucky University on July 4, 2015
tested for, and 37% had HPV 16 or 18. The incidence of anal HPV infection in this group was 38.5 and 15.3 per 1000 person-months for any and HPV 16 and 18, respectively [13]. As with the current study, HPV prevalence was significantly associated with increasing number of receptive anal intercourse (RAI) sexual partners. These study findings mirror studies in teenage girls where there is a rapid accumulation of HPV types following sexual debut that increases with partner number, indicating both high HPV prevalence and ease of transmission of the virus [14, 15]. In Zou et al’s study, both HPV and warts were more commonly detected in the anal canal than the penis, with the anal canal also having the highest proportion of qHPV-preventable HPV types. It is possible that the anal canal is a more “vulnerable” site for HPV infection, with higher rates also found compared to the cervix in HIV-positive women, and increased length of detectable infection found anally in HIV-positive MSM [4, 16]. Penile HPV was more common in participants who had a history of vaginal intercourse, and increased significantly with the number of insertive anal and vaginal sex partners. The authors also identified circumcision status as influencing HPV detection, with a trend toward higher HPV detection in uncircumcised versus circumcised participants (P = .059). Rates of oral HPV infection in the Zou et al study were low, as expected from comparable populations [17]. Although the rate of HPV-associated oropharyngeal cancer has increased dramatically in recent years, with risk factors including number of oral sex partners and HIV infection, the effect of HPV vaccination on oral HPV infection is as yet unknown [18–20]. HPV DNA detection does not differentiate “deposition”; for example, from a recent partner that may never form an active infection, from established infection. It is, therefore, possible that the HPV prevalence data presented in the article by Zou et al overestimates actual
Note Potential conflicts of interest. R. D. C. has received grant funding from Merck and Co. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med 1997; 102:3–8. 2. Myers ER, McCrory DC, Nanda K, Bastian LMatchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol 2000; 151:1158–71. Epub 2000/ 07/25. 3. Moscicki AB, Schiffman M, Burchell A, et al. Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 2012; 30(suppl 5):F24–33. Epub 2012/12/05. 4. de Pokomandy A, Rouleau D, Ghattas G, et al. Prevalence, clearance, and incidence of anal human papillomavirus infection in HIV-infected men: the HIPVIRG cohort study. J Infect Dis 2009; 199:965–73. Epub 2009/02/26.
5. Giuliano AR, Lazcano-Ponce E, Villa LL, et al. The human papillomavirus infection in men study: human papillomavirus prevalence and type distribution among men residing in Brazil, Mexico, and the United States. Cancer Epidemiol Biomarkers Prev 2008; 17:2036–43. Epub 2008/08/19. 6. Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE study. J Infect Dis 2004; 190:2070–6. 7. Daling JR, Weiss NS, Hislop TG, et al. Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 1987; 317:973–7. 8. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007; 356:1928–43. Epub 2007/05/15. 9. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365:1576–85. Epub 2011/10/28. 10. Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247–55. Epub 2006/04/25. 11. Frazer I. Correlating immunity with protection for HPV infection. Int J Infect Dis 2007; 11(Suppl 2):S10–6. Epub 2008/03/08. 12. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757–65. 13. Glick SN, Feng Q, Popov V, Koutsky LA, Golden MR. High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men. J Infect Dis 2013. Epub 2013/08/21. 14. Herrero R, Castle PE, Schiffman M, et al. Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. J Infect Dis 2005; 191:1796–807. Epub 2005/05/05. 15. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001; 357:1831–6. Epub 2001/06/19. 16. Palefsky JM, Holly EA, Ralston ML, Da Costa M, Greenblatt RM. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)–positive and high-risk HIV-negative women. J Infect Dis 2001; 183:383–91. 17. Nordfors C, Grun N, Haeggblom L, et al. Oral human papillomavirus prevalence in high school students of one municipality in Sweden. Scand J Infect Dis 2013; 45:878–81. Epub 2013/08/21.
18. Anthonsen S, Larsen J, Pedersen PL, Dalgaard LT, Kvetny J. Basal and T(3)-induced ROS production in lymphocyte mitochondria is increased in type 2 diabetic patients. Horm Metab Res 2013; 45:261–6. Epub 2012/09/28. 19. Hillman RJ, Giuliano AR, Palefsky JM, et al. Immunogenicity of the quadrivalent human papillomavirus (type 6/11/16/18) vaccine in males 16 to 26 years old. Clin Vaccine Immunol 2012; 19:261–7. Epub 2011/12/14. 20. Palefsky JM, Gonzales J, Greenblatt RM, Ahn DK, Hollander H. Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV HIV disease. JAMA 1990; 263:2911–6. 21. Szarewski A, Ambroisine L, Cadman L, et al. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomarkers Prev 2008; 17:3033–42. Epub 2008/ 10/30. 22. Meites E, Krishna NK, Markowitz LE, Oster AM. Health care use and opportunities for human papillomavirus vaccination among young men who have sex with men. Sex Transm Dis 2013; 40:154–7. Epub 2013/ 01/17. 23. Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus vaccination in the United Kingdom. BMJ 2008; 337: a769. Epub 2008/07/22. 24. Kim JJ, Goldie SJ. Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States. BMJ 2009; 339:b3884. Epub 2009/10/10. 25. Taira AV, Neukermans CP, Sanders GD. Evaluating human papillomavirus vaccination programs. Emerg Infect Dis 2004; 10:1915–23. Epub 2004/11/20. 26. Kim JJ. Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis. Lancet Infect Dis 2010; 10:845–52. Epub 2010/11/06. 27. Gutierrez B Jr, Leung A, Jones KT, et al. Acceptability of the human papillomavirus vaccine among urban adolescent males. Am J Men’s Health 2013; 7:27–36. Epub 2012/ 08/16. 28. Newman PA, Logie CH, Doukas N, Asakura K. HPV vaccine acceptability among men: a systematic review and meta-analysis. Sex Transm Infect 2013; 89:568–74. Epub 2013/ 07/06. 29. Sinka K, Kavanagh K, Gordon R, et al. Achieving high and equitable coverage of adolescent HPV vaccine in Scotland. J Epidemiol Community Health 2013. Epub 2013/ 08/30. 30. Health Do. Annual HPV vaccine coverage in England in 2009/2010. 2011; (15439). 31. Kessels SJ, Marshall HS, Watson M, Braunack-Mayer AJ, Reuzel R, Tooher RL. Factors associated with HPV vaccine uptake in teenage girls: a systematic review. Vaccine 2012; 30:3546–56. Epub 2012/04/07.
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age 15 years. The effect of the female vaccination program has already shown a reduction in female wart diagnoses of 59% and 39% in female and male Australian Nationals, respectively, between 2004 and 2009, with no change in wart diagnoses in Australian non-Nationals [32, 33]. Moreover, a recent modeling study examining the effect of this new vaccination policy predicts the future virtual elimination of genital warts in Australian National females and heterosexual males [34]. Currently available HPV vaccines are safe, immunogenic, and highly effective if given before and after limited HPV exposure. Vaccination policy options for men include either a general or focused strategy. Targeting an MSM demographic, while appropriate because of both high HPV risk and acceptable cost effectiveness, has clear operational challenges. In a bold move, the Australian government has extended its successful HPV vaccination initiative for Australian Nationals and now provides qHPV coverage to all school-age boys. Over time we will all learn, and most likely envy, the consequences of this action.
32. Georgousakis M, Jayasinghe S, Brotherton J, Gilroy N, Chiu C, Macartney K. Populationwide vaccination against human papillomavirus in adolescent boys: Australia as a case study. Lancet Infect Dis 2012; 12:627–34. Epub 2012/03/27.
33. Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011; 11:39–44. Epub 2010/11/12.
34. Korostil IA, Ali H, Guy RJ, Donovan B, Law MGRegan DG. Near elimination of genital warts in Australia predicted with extension of human papillomavirus vaccination to males. Sex Transm Dis 2013; 40:833–5. Epub 2013/10/12.
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EDITORIAL COMMENTARY
Young Gay Men and the Quadrivalent Human Papillomavirus Vaccine—Much to Gain (and Lose) Ross D. Cranston Department of Medicine, University of Pittsburgh, Pennsylvania
(See the major article by Huachun et al on pages 642–51.)
Keywords.
Human papillomavirus (HPV); vaccine; gay men; quadrivalent; anogenital.
Received and accepted 4 November 2013; electronically published 21 November 2013. Correspondence: Ross D. Cranston, MB ChB, MD, FRCP, University of Pittsburgh, 3520 Fifth Ave, Keystone Bldg, Ste 510, Pittsburgh, PA 15213 ([email protected]). The Journal of Infectious Diseases 2014;209:635–8 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jit627
rates of anogenital HPV infection and also HPV-associated malignancy, particularly HPV 16–associated anal cancer [6, 7]. HPV vaccination has been shown to be safe and effective in preventing the acquisition of anogenital HPV infection and the development of dysplasia [8–10]. The challenge ahead is to ensure that vaccinations are available to those at risk in a manner that optimizes their efficacy. There are 2 licensed HPV vaccines: a bivalent vaccine directed against HPV 16 and 18 (Cervarix, GlaxoSmithKline, London, UK) licensed for females aged 9–25 years, and a quadrivalent HPV vaccine (qHPV) directed against HPV 6, 11, 16, and 18 (Gardasil, Merck, Whitehouse Station, NJ) licensed for females and males ages 9–26 years. Both vaccines’ indications include prevention of warts and female genital dysplasia/cancer, with qHPV also indicated for anal dysplasia/ cancer. These prophylactic vaccines induce high-titer HPV antibody levels with good efficacy and an excellent safety profile [11, 12]. In this issue of The Journal of Infectious Diseases, Zou and colleagues examined acquisition of anogenital HPV in a population of MSM. They enrolled men between the ages of 16 and 20 years who self-identified as same-sex attracted. Thus, they were able to assess incident HPV infection in MSM with limited sexual experience who might benefit from HPV vaccination if they had the
same access to HPV vaccines as adolescent girls. Following recruitment from a variety of venues, participants were seen for assessments at baseline and then at 3, 6, and 12 months. At each visit, participants had a clinical exam, completed a sexual experience questionnaire, had a blood sample drawn for HPV serology, and swabs taken from penile, perianal, and intra-anal sites. An oral saline gargle was also collected. All these samples were tested for HPV DNA by polymerase chain reaction. Additionally, participants were tested for gonorrhea, chlamydia, syphilis, and HIV at each visit. At the 12-month visit, participants were offered the qHPV. The median age of study participants was 19 years and the majority had engaged in both receptive and insertive anal intercourse. Thirty-nine percent of participants had at least 1 of 37 HPV types tested for at the anatomical sites sampled, and 23% had at least 1 qHPV type. Overall, at least 1 high-risk HPV was detected in 31% of participants. In participants with 0 to ≥4 receptive and insertive anal-sex partners, the respective proportion of anal (P < .001) and penile (P < .014) HPV increased significantly. This trend also reached significance for detection of anal HPV 16. In another study conducted in a slightly older age group of 94 MSM with a mean age of 21 years, 70% had any of the 37 HPV types
EDITORIAL COMMENTARY
•
JID 2014:209 (1 March)
•
635
Downloaded from http://jid.oxfordjournals.org/ at Northern Kentucky University on July 4, 2015
Human papillomavirus (HPV) is the world’s most common viral sexually transmitted infection [1, 2]. Approximately 40 HPV types infect anogenital squamous epithelium and can be broadly divided into low-risk (eg, HPV 6, 11) and high-risk (eg, HPV 16, 18) phenotypes based on their historical association with cervical cancer. This relationship also holds true for other anogenital (anal, vulvar, vaginal) and oropharyngeal malignancies. Although most HPV infections are asymptomatic, when symptoms do occur, they often reflect the presence of warts, dysplasia, or frank malignancy. Anogenital HPV infection is mostly transient in both sexes, with persistent high-risk HPV infection associated with the development of squamous-cell cancers [3, 4]. HPV prevalence data vary by gender, with men being more likely to have higher-level detection over a wider age range than women, whose prevalence decreases from a peak in their early 20s [3, 5] However, it is men who have sex with men (MSM) who have the highest
636
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JID 2014:209 (1 March)
•
HPV presence, and may contribute to the explanation of why 10% of participants with anal HPV reported no RAI. There was also a low/moderate correlation of DNA detection and serology that may also reflect a delay in developing a serological response. Newer testing platforms that detect HPV mRNA may be more predictive of established infection than the detection of HPV DNA alone [21]. In the absence of routine vaccination of school-age boys aged 12–13 years, individuals would have to actively seek vaccination from a health care provider based on their self-identification as MSM. In this study, participants were asked if they would be willing to identify as MSM in order to access HPV vaccination, and 85.5% agreed, although only 55.5% had previously disclosed their sexuality to their primary care physician. This is similar to data from the US National HIV Behavioral Surveillance System that indicated almost 90% of young MSM had used health care in the last 12 months, but only 61.3% disclosed their sexuality to the provider [22] Almost 20% of participants in the current study had experienced vaginal sex, suggesting that sexuality identity had not yet fully formed or that the individual’s sexuality was more fluid. In both cases, the individual may be exposed to HPV before seeking a vaccine specifically aimed at a MSM demographic. Cost-effective analyses of the widespread vaccination of boys have consistently shown that there is no benefit beyond that achieved by high rates of vaccine uptake in girls, and induction of herd immunity [23–25]. However, this will likely have little if any effect on HPV infection in MSM, leaving an unprotected demographic with the greatest risk of HPV infection and its complications. However, when MSM are considered in isolation, vaccination becomes cost effective based on the standard parameter of costing less than US$50 000 per qualityadjusted life-year [26]. However, in these models, the cost effectiveness wanes as age at vaccination, sexual partner number,
EDITORIAL COMMENTARY
and HPV prevalence increase. The licensure studies of qHPV in MSM are instructive, as they enrolled a broadly similar cohort of participants to the Zou et al study (ie, MSM aged 16–26 years who had ≤5 sex partners). Both the per protocol (with no serological or DNA evidence of HPV infection) and intent-to-treat analyses demonstrated efficacy for the prevention of qHPV types, as well as for the prevention of warts and both low- and high-grade anal dysplasia [9]. Thus, despite the HPV exposure in the Zou et al study, vaccination of individuals may be of benefit, albeit at a reduced rate compared to non-HPV–exposed individuals. This finding is particularly important when considering a focused MSM vaccine strategy where individuals self-identifying as MSM who request the qHPV would most likely have encountered HPV infection through prior sexual activity. The Zou et al study offered qHPV to all study participants at the 12-month visit, with an uptake rate of 96%. Whereas MSM have been shown to be more knowledgeable about HPV than heterosexual men, their self-perception of willingness to be vaccinated was only moderate in a meta-analysis of 29 studies [27, 28]. Rates of uptake of HPV vaccination are strongly correlated to the ease with which potential recipients can access vaccination. For females in Scotland and England where vaccination is free and offered to school-age girls, coverage is over 70% for completion of all 3 vaccinations [29, 30]. In the United States, coverage for girls critically depends upon venue of administration, with school-based systems achieving higher coverage than other strategies [31]. The Australian government has been extremely active in addressing HPV infection, with the National Immunization Program instituting a free vaccination program for Australian National girls aged 12–13 years in 2007, with catch-up vaccination possible up to age 26 years until 2009. In February 2013, this program was extended to boys aged 12–13 years, with catch-up vaccination possible up to
Downloaded from http://jid.oxfordjournals.org/ at Northern Kentucky University on July 4, 2015
tested for, and 37% had HPV 16 or 18. The incidence of anal HPV infection in this group was 38.5 and 15.3 per 1000 person-months for any and HPV 16 and 18, respectively [13]. As with the current study, HPV prevalence was significantly associated with increasing number of receptive anal intercourse (RAI) sexual partners. These study findings mirror studies in teenage girls where there is a rapid accumulation of HPV types following sexual debut that increases with partner number, indicating both high HPV prevalence and ease of transmission of the virus [14, 15]. In Zou et al’s study, both HPV and warts were more commonly detected in the anal canal than the penis, with the anal canal also having the highest proportion of qHPV-preventable HPV types. It is possible that the anal canal is a more “vulnerable” site for HPV infection, with higher rates also found compared to the cervix in HIV-positive women, and increased length of detectable infection found anally in HIV-positive MSM [4, 16]. Penile HPV was more common in participants who had a history of vaginal intercourse, and increased significantly with the number of insertive anal and vaginal sex partners. The authors also identified circumcision status as influencing HPV detection, with a trend toward higher HPV detection in uncircumcised versus circumcised participants (P = .059). Rates of oral HPV infection in the Zou et al study were low, as expected from comparable populations [17]. Although the rate of HPV-associated oropharyngeal cancer has increased dramatically in recent years, with risk factors including number of oral sex partners and HIV infection, the effect of HPV vaccination on oral HPV infection is as yet unknown [18–20]. HPV DNA detection does not differentiate “deposition”; for example, from a recent partner that may never form an active infection, from established infection. It is, therefore, possible that the HPV prevalence data presented in the article by Zou et al overestimates actual
Note Potential conflicts of interest. R. D. C. has received grant funding from Merck and Co. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med 1997; 102:3–8. 2. Myers ER, McCrory DC, Nanda K, Bastian LMatchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol 2000; 151:1158–71. Epub 2000/ 07/25. 3. Moscicki AB, Schiffman M, Burchell A, et al. Updating the natural history of human papillomavirus and anogenital cancers. Vaccine 2012; 30(suppl 5):F24–33. Epub 2012/12/05. 4. de Pokomandy A, Rouleau D, Ghattas G, et al. Prevalence, clearance, and incidence of anal human papillomavirus infection in HIV-infected men: the HIPVIRG cohort study. J Infect Dis 2009; 199:965–73. Epub 2009/02/26.
5. Giuliano AR, Lazcano-Ponce E, Villa LL, et al. The human papillomavirus infection in men study: human papillomavirus prevalence and type distribution among men residing in Brazil, Mexico, and the United States. Cancer Epidemiol Biomarkers Prev 2008; 17:2036–43. Epub 2008/08/19. 6. Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE study. J Infect Dis 2004; 190:2070–6. 7. Daling JR, Weiss NS, Hislop TG, et al. Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 1987; 317:973–7. 8. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007; 356:1928–43. Epub 2007/05/15. 9. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365:1576–85. Epub 2011/10/28. 10. Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247–55. Epub 2006/04/25. 11. Frazer I. Correlating immunity with protection for HPV infection. Int J Infect Dis 2007; 11(Suppl 2):S10–6. Epub 2008/03/08. 12. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757–65. 13. Glick SN, Feng Q, Popov V, Koutsky LA, Golden MR. High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men. J Infect Dis 2013. Epub 2013/08/21. 14. Herrero R, Castle PE, Schiffman M, et al. Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. J Infect Dis 2005; 191:1796–807. Epub 2005/05/05. 15. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001; 357:1831–6. Epub 2001/06/19. 16. Palefsky JM, Holly EA, Ralston ML, Da Costa M, Greenblatt RM. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)–positive and high-risk HIV-negative women. J Infect Dis 2001; 183:383–91. 17. Nordfors C, Grun N, Haeggblom L, et al. Oral human papillomavirus prevalence in high school students of one municipality in Sweden. Scand J Infect Dis 2013; 45:878–81. Epub 2013/08/21.
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age 15 years. The effect of the female vaccination program has already shown a reduction in female wart diagnoses of 59% and 39% in female and male Australian Nationals, respectively, between 2004 and 2009, with no change in wart diagnoses in Australian non-Nationals [32, 33]. Moreover, a recent modeling study examining the effect of this new vaccination policy predicts the future virtual elimination of genital warts in Australian National females and heterosexual males [34]. Currently available HPV vaccines are safe, immunogenic, and highly effective if given before and after limited HPV exposure. Vaccination policy options for men include either a general or focused strategy. Targeting an MSM demographic, while appropriate because of both high HPV risk and acceptable cost effectiveness, has clear operational challenges. In a bold move, the Australian government has extended its successful HPV vaccination initiative for Australian Nationals and now provides qHPV coverage to all school-age boys. Over time we will all learn, and most likely envy, the consequences of this action.
32. Georgousakis M, Jayasinghe S, Brotherton J, Gilroy N, Chiu C, Macartney K. Populationwide vaccination against human papillomavirus in adolescent boys: Australia as a case study. Lancet Infect Dis 2012; 12:627–34. Epub 2012/03/27.
33. Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011; 11:39–44. Epub 2010/11/12.
34. Korostil IA, Ali H, Guy RJ, Donovan B, Law MGRegan DG. Near elimination of genital warts in Australia predicted with extension of human papillomavirus vaccination to males. Sex Transm Dis 2013; 40:833–5. Epub 2013/10/12.
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