Abstract:

Objective:

Describe the natural history of anal HPV among men.

Materials and methods:

Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months.

Results:

Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12-9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4-6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1 000 person-months (95%CI:6.0-10.1), HPV16=1.8/1 000 person-months (95%CI:1.1-2.9),4vHPV=3.4/1 000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5).

Conclusions:

Implementation of universal HPV vaccination programs, including men, is a public health priority.

Kewords:
human papilloma virus; prevalence; incidence; anal canal; men; apillomavirus vaccines

Resumen:

Objetivo:

Generar evidencia que apoye la vacunación universal contra VPH.

Material y métodos:

Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes.

Resultados:

Prevalencia de infección anal: cualquier tipo de VPH=15%, alto-riesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4-6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses.

Conclusiones:

Implementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Palabras clave
virus del papiloma humano; prevalencia; incidencia; canal anal; hombres; vacunación universal contra VPH

Introduction

In men, human papillomavirus (HPV) infections are associated with genital warts and intraepithelial neoplasm, predominantly in the anal canal.¹1. Fuchs W, Wieland U, Skaletz-Rorowski A, Brockmeyer NH, Swoboda J, Kreuter A, et al. The male ScreenING Study: prevalence of HPV-related genital and anal lesions in an urban cohort of HIV-positive men in Germany. J Eur Acad Dermatol Venereol. 2016;30(6):995-1001. https://doi.org/10.1111/jdv.13539
https://doi.org/10.1111/jdv.13539... Quantification of HPV prevalence and incidence in the anal canal has been described for heterosexual men,²2. Pamnani SJ, Nyitray AG, Abrahamsen M, Rollison DE, Villa LL, Lazcano-Ponce E, et al. Sequential acquisition of anal human papillomavirus (HPV) infection following genital infection among men who have sex with women: The HPV infection in men (HIM) Study. J Infect Dis. 2016;214(8):1180-7. https://doi.org/10.1093/infdis/jiw334
https://doi.org/10.1093/infdis/jiw334... men who have sex with men (MSM),³3. Nyitray AG, Carvalho Da Silva RJ, Chang M, Baggio ML, Ingles DJ, Abrahamsen M, et al. Incidence, duration, persistence, and factors associated with high-risk anal human papillomavirus persistence among HIV-negative men who have sex with men: A multinational study. Clin Infect Dis. 2016;62(11):1367-74. https://doi.org/10.1093/cid/ciw140
https://doi.org/10.1093/cid/ciw140... bisexual men⁴4. Nyitray AG, da Silva RJ, Baggio ML, Lu B, Smith D, Abrahamsen M, et al. The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: the HIM study. Sex Transm Dis. 2011;38(10):932-40. https://doi.org/10.1097/OLQ.0b013e31822154f9
https://doi.org/10.1097/OLQ.0b013e318221... and transpeople⁵5. Loverro G, Di Naro E, Caringella AM, De Robertis AL, Loconsole D, Chironna M. Prevalence of human papillomavirus infection in a clinic sample of transsexuals in Italy. Sex Transm Infect. 2016;92(1):67-9. https://doi.org/10.1136/sextrans-2014-051987
https://doi.org/10.1136/sextrans-2014-05... as well as in men with HIV⁶6. Torres-Ibarra L, Conde-Glez CJ, Salmerón J, Palefsky J, Hernández-Nevares P, Sánchez-Alemán MA, et al. Risk factors for anal HPV-16/18 infection in Mexican HIV-infected men who have sex with men. Prev Med (Baltim). 2014;69:157-64. https://doi.org/10.1016/j.ypmed.2014.09.011
https://doi.org/10.1016/j.ypmed.2014.09.... and immunosurpressed people.⁷7. Bernat-García J, Morales Suárez-Varela M, Vilata-Corell JJ, Marquina-Vila A. Detection of human papillomavirus in nonmelanoma skin cancer lesions and healthy perilesional skin in kidney transplant recipients and immunocompetent patients. Actas Dermosifiliogr. 2014;105(3):286-94. https://doi.org/10.1016/j.ad.2013.10.011
https://doi.org/10.1016/j.ad.2013.10.011... In many of these population groups, the frequency of high- and low-risk HPV is extremely high; this can lead not only to a greater likelihood of transmitting HPV to their sexual partners⁸8. Morales R, Parada R, Giuliano AR, Cruz A, Castellsagué X, Salmeroń J, et al. HPV in female partners increases risk of incident HPV infection acquisition in heterosexual men in rural central Mexico. Cancer Epidemiol Biomarkers Prev. 2012;21(11):1956-65. https://doi.org/10.1158/1055-9965.EPI-12-0470
https://doi.org/10.1158/1055-9965.EPI-12... but also to increased risk of anal intraepithelial neoplasm.⁹9. Sendagorta E, Herranz P, Guadalajara H, Bernardino JI, Viguer JM, Beato MJ, et al. Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men. Dis Colon Rectum. 2014;57(4):475-81. https://doi.org/10.1097/DCR.0000000000000095
https://doi.org/10.1097/DCR.000000000000...

Sexual behaviors are the main determinants of incident HPV infections; also, the HIV population is more likely to have a persistent infection in the anal canal; the largest burden of HPV related diseases is found in people with HIV.¹⁰10. Müller EE, Rebe K, Chirwa TF, Struthers H, McIntyre J, Lewis DA. The prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town, South Africa. BMC Infect Dis. 2016;16(1):440. https://doi.org/10.1186/s12879-016-1706-9
https://doi.org/10.1186/s12879-016-1706-... In addition, heterosexual men with genital HPV infections are at greater risk of infection in the anal canal; autoinoculation is, hypothetically, a mechanism which could explain this last association.³3. Nyitray AG, Carvalho Da Silva RJ, Chang M, Baggio ML, Ingles DJ, Abrahamsen M, et al. Incidence, duration, persistence, and factors associated with high-risk anal human papillomavirus persistence among HIV-negative men who have sex with men: A multinational study. Clin Infect Dis. 2016;62(11):1367-74. https://doi.org/10.1093/cid/ciw140
https://doi.org/10.1093/cid/ciw140... Studies indicate that frequency of HPV in the anal canal is associated with increased incidence and mortality due to anal cancer in higher-income countries. For example, in 2008-2012 in the United States there was an annual average of 1 600 cases of anal cancer in men attributable to HPV.¹¹11. Viens LJ, Henley SJ, Watson M, Markowitz LE, Thomas CC, Thompson TD, et al. Human Papillomavirus-Associated Cancers-United States, 2008-2012. MMWR Morb Mortal Wkly Rep. 2016;65(26):661-6. https://doi.org/10.15585/mmwr.mm6526a1
https://doi.org/10.15585/mmwr.mm6526a1... Likewise, since people with HIV are living longer due to anti-retroviral treatments, their risk for developing HPV-related lesions, and consequently cancer in the ano-genital region, has multiplied.¹²12. Kreuter A, Siorokos C, Oellig F, Silling S, Pfister H, Wieland U. High-grade dysplasia in anogenital warts of HIV-positive men. JAMA Dermatol. 2016;152(11):1225-30. https://doi.org/10.1001/jamadermatol.2016.2503
https://doi.org/10.1001/jamadermatol.201...

Given the above, recently some parts of the world have implemented public policies on population-level vaccination against HPV that include coverage of men.¹³13. Reynoso-Noverón N, Meneses-García A, Erazo-Valle A, Escudero-de los Ríos P, Kuri-Morales PA, Mohar-Betancourt A. Challenges in the development and implementation of the National Comprehensive Cancer Control Program in Mexico. Salud Publica Mex. 2016;58:325-333. https://doi.org/10.21149/spm.v58i2.7804
https://doi.org/10.21149/spm.v58i2.7804... The desired impact of these policies can be framed from a number of perspectives: gender equity,¹⁴14. Brotherton JML, Batchelor MR, Bradley MO, Brown SA, Duncombe SM, Meijer D, et al. Interium estimates of male human papillomavirus vaccination coverage in the school-based program in Australia. Commun Dis Intell Q Rep. 2015;39(2):E197-200. increased universal coverage,¹⁵15. Nanagas VC, Stolfi A, Nanagas MT, Eberhart GM, Alter SJ. Adolescent Male Human Papillomavirus Vaccination. Glob Pediatr Health. 2016;3:2333794X16642373. or protection of people who are at greater risk of HPV and associated negative outcomes.¹⁶16. Camacho-Gonzalez AF, Chernoff MC, Williams PL, Chahroudi A, Oleske JM, Traite S, et al. Sexually transmitted infections in youth with controlled and uncontrolled human immunodeficiency virus infection. J Pediatric Infect Dis Soc. 2017;6(3):e22-e29. https://doi.org/10.1093/ipids/piw039
https://doi.org/10.1093/ipids/piw039... This article describes findings on the prevalence and incidence of infections in the anal canal with specific HPV types among Mexican men who participated in an international research initiative known as the HIM study.¹⁷17. Giuliano AR, Lee J-H, Fulp W, Villa LL, Lazcano E, Papenfuss MR, et al. Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study. Lancet. 2011;377(9769):932-40.^,1818. Giuliano AR, Lazcano-Ponce E, Villa LL, Flores R, Salmeron J, Lee JH, 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(8):2036-43.

Materials and methods

Study population and design

The HIM Study provides prospective data on the evolution of HPV infection in men. Within this study, 4 074 men aged 18-70 years were recruited in three countries; a total of 1 330 participants were included in Mexico.¹⁷17. Giuliano AR, Lee J-H, Fulp W, Villa LL, Lazcano E, Papenfuss MR, et al. Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study. Lancet. 2011;377(9769):932-40.^,1818. Giuliano AR, Lazcano-Ponce E, Villa LL, Flores R, Salmeron J, Lee JH, 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(8):2036-43. A detailed description of the general HIM study has been published previously.¹⁷17. Giuliano AR, Lee J-H, Fulp W, Villa LL, Lazcano E, Papenfuss MR, et al. Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study. Lancet. 2011;377(9769):932-40.^,1818. Giuliano AR, Lazcano-Ponce E, Villa LL, Flores R, Salmeron J, Lee JH, 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(8):2036-43.^,1919. Ishibashi MA, Antunes JA, Aoki MFC, Terreri RB, Brito E, Silva RC, et al. Human Papillomavirus infection in men residing in Brazil, Mexico, and the USA. Salud Publica Mex . 2008;50(5):408-18. In Mexico, participants were recruited in the city of Cuernavaca located in the central state of Morelos. The informed consent of all the participants was obtained. For this analysis, 665 men were included who had at least two study visits for sample collection from the anal canal between November 2005 and December 2010. The ethics, biosecurity and research committees of the Instituto Nacional de Salud Pública and the Instituto Mexicano del Seguro Social (IMSS) approved the research protocol. Men who had an existing penile or anal cancer diagnosis, symptoms or previous treatment of a sexually transmitted infection, or a history of genital or anal warts, and HIV-positive individuals were excluded from the study. Men from different population groups were recruited, including university students, healthcare users, and members of organized healthcare systems (particularly the IMSS).

Study procedures

During all follow-up visits, participants completed a computer-assisted self-interview (CASI) questionnaire designed to collect data on social and behavioral variables related to HPV infection, including condom use, lifetime male and female sex partners, new sex partners, and tobacco and alcohol use.³3. Nyitray AG, Carvalho Da Silva RJ, Chang M, Baggio ML, Ingles DJ, Abrahamsen M, et al. Incidence, duration, persistence, and factors associated with high-risk anal human papillomavirus persistence among HIV-negative men who have sex with men: A multinational study. Clin Infect Dis. 2016;62(11):1367-74. https://doi.org/10.1093/cid/ciw140
https://doi.org/10.1093/cid/ciw140... In addition, a physical exam was carried out, and samples were collected for laboratory analysis for HPV diagnosis; up to 10 clinical visits, scheduled every 6 months during a 4-year follow-up period, were conducted. Urine, blood, anogenital epithelium and oral samples were collected. Separate saline-wetted Dacron swabs were used to collect exfoliated skin cells from the penis (i.e., coronal sulcus, glans, and ventral and dorsal areas of shaft) and scrotum. Then, using a separate swab, 360° of the anal epithelium was swabbed between the anal os and the anal canal dentate line. Gloves were changed after each sample was collected, and each swab was placed into a separate vial with standard transport medium and stored at -80°C until processing at the lab in Tampa, Florida.²⁰20. Nyitray AG, Carvalho da Silva RJ, Baggio ML, Lu B, Smith D, Abrahamsen M, et al. Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: the HPV in men (HIM) study. J Infect Dis. 2011;203(1):49-57. https://doi.org/10.1093/infdis/jiq021
https://doi.org/10.1093/infdis/jiq021... All personnel were trained in sample collection, emphasizing the importance of avoiding touching the perianal skin with the swab.

HPV Detection

Samples were analyzed for HPV DNA as described above.¹⁸18. Giuliano AR, Lazcano-Ponce E, Villa LL, Flores R, Salmeron J, Lee JH, 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(8):2036-43. Briefly, DNA was extracted using the QIAamp Media MDx kit (Qiagen). The polymerase chain reaction (PCR) consensus primer system (PGMY 09/11) was used to amplify a fragment of the HPV L1 gene.²¹21. Gravitt PE, Peyton CL, Alessi TQ, Wheeler CM, Coutlée F, Hildesheim A, et al. Improved amplification of genital human papillomaviruses. J ClinMicrobiol. 2000; 38:357-61. HPV genotyping was conducted on all samples using DNA probes labeled with biotin in order to detect 37 HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51-56, 58, 59, 61, 62, 64, 66-73, 81-84, IS39, and CP6108.²²22. Gravitt PE, Peyton CL, Apple RJ, Wheeler CM. Genotyping of 27 human papilloma virus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol. 1998;36:3020-7. Accuracy and potential contamination were assessed using non-template negative controls and CaSki DNA-positive controls.²⁰20. Nyitray AG, Carvalho da Silva RJ, Baggio ML, Lu B, Smith D, Abrahamsen M, et al. Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: the HPV in men (HIM) study. J Infect Dis. 2011;203(1):49-57. https://doi.org/10.1093/infdis/jiq021
https://doi.org/10.1093/infdis/jiq021...

Statistical analysis

Prevalence and incidence were estimated for any HPV type -whether high-risk (HR-HPV: 16/18/31/33/35/39/45/51/52/56/58/59/68) or low-risk (LR-HPV: 6/11/26/40/42/53/54/55/61/62/64/66/67/69/70/71/72/73/81/82/IS39/83/84/89)-, for the four types (6/11/16/18) included in the tetravalent HPV vaccine (4vHPV), for the nine types (6/11/16/18/31/33/45/52/58) included in the nonavalent HPV vaccine (9vHPV), and for each specific HPV type. The classification of any HPV infection was defined as a positive test result for at least one of 37 HPV genotypes. HPV infections with single or multiple high-risk virus types were classified as high-risk.²³23. Cogliano V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F. WHO International Agency for Research on Cancer. Carcinogenicity of human papilloma viruses. Lancet Oncol. 2005;6(4):204. https://doi.org/10.1016/S1470-2045(05)70086-3
https://doi.org/10.1016/S1470-2045(05)70...

In order to assess factors associated with prevalent HPV infection, prevalence ratios (PRs) and 95%CI were calculated with Poisson regression using robust variance estimation. Age was forced into the multivariable model, while other factors that remained in the final model were p<0.05.

Person-time for newly acquired HPV infection was estimated by use of time from study entry to the date of the first detection of HPV DNA, assuming a new infection arose at the date of detection. The calculation of the exact 95%CI for incidence estimates was based on the number of events modeled as a Poisson variable for the total person-months.

Results

Anal HPV infections (with any HPV type) were detected at baseline in 100 out of the 665 Mexican men included in this analysis; i.e. the prevalence of these infections was 15% (table I). Prevalence of HPV infection in the anal canal was 8.4% for high-risk (oncogenic) HPV types, and 10.7% for low-risk (non-oncogenic) types. Among the specific HPV types with the highest prevalence in the anal canal were HPV-16 (1.4%) and HPV-6 (2.3%). The HIM Study found in Mexican men a prevalence of 4.4% of infection in the anal canal with one or more of the HPV types included in the tetravalent HPV vaccine, and of 6.3% of infection with one or more of the HPV types included in the nonavalent vaccine.

There were statistically significant differences between men with and without a prevalent HPV infection in the anal canal, in terms of age (p=0.03), marital status (p=0.01), sexual orientation (p<0.0001) and lifetime number of male partners (p<0.0001) (table II). No differences between men with and without a prevalent HPV infection were observed for the other characteristics.

Among Mexican men in the HIM Study, the factors associated with prevalent infection with any HPV type in the anal canal were: having had more than 50 female sex partners in their lifetime, compared with 1 or fewer lifetime female sexual partners (adjusted prevalence ratio, aPR=3.25, 95%CI 1.12-9.47); having had 1-9 male anal sex partners in their lifetime (aPR=1.84, 95%CI 1.07-3.17) or 10 or more male anal sex partners in their lifetime (aPR=3.06, 95%CI 1.4-6.68), both compared to no male sexual partners, and having had one or more recent male anal sex partners, compared to no recent male sexual partners (aPR=2.28, 95%CI 1.15-4.5) (table II).

Statistically significant differences between men with and without an incident HPV infection (of any type acquired after baseline) in the anal canal were observed for marital status (p<0.0001), sexual orientation (p<0.0001) and lifetime number of male sex partners (p<0.0001) (table III).

The incidence rate for anal infection with any type of HPV was 11.0/1 000 person-months (95%CI 8.7-14.0), while the incidence rate for anal infection for high-risk HPV types was 7.8/1000 person-months (95%CI 6.0-10.1), and 8.4/1000 person-months (95%CI 6.5-10.9) for low-risk HPV types (table IV). The incidence rate specifically for one or more of the HPV types included in the tetravalent HPV vaccine was 3.4/1 000 person-months (95%CI 2.3-4.9), and 5.5/1000 person-months (95%CI 4.1-7.5) for one or more of the HPV types included in the nonavalent vaccine.

Discussion

Prevalence of HPV infections in the anal canal among Mexican men was 15%. The rate at which new (incident) infections were acquired was 11 new infections per 1 000 person-months. Among Mexican men, the factors associated with prevalent HPV infection in the anal canal were related to sexual behavior, above all to having multiple sexual partners, especially male anal sex partners.

Before the HIM Study cohort was developed to describe the natural history of HPV infection in men, the existing publications on epidemiological studies established hypotheses about the factors associated with HPV infection in the ano-genital region in men. Based on cross-sectional studies and on the initial stages of cohort studies, the scientific community knew that HPV infections in the anal canal in men were closely associated to certain sexual behaviors,²⁴24. Tejada RA, Vargas KG, Benites-Zapata V, Mezones-Holguín E, Bolaños-Díaz R, Hernández AV. Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis. Salud Publica Mex . 2017;59:84-94. https://doi.org/10.21149/7824
https://doi.org/10.21149/7824... such as having multiple sexual partners,²⁵25. Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, van den Brule AJ. 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(3):215-8. https://doi.org/10.1136/sti.78.3.215
https://doi.org/10.1136/sti.78.3.215... and also to the frequency with which men had contact with new sexual partners.²⁶26. Partridge JM, Hughes JP, Feng Q, Winer RL, Weaver BA, Xi LF, et al. Genital human papillomavirus infection in men: incidence and risk factors in a cohort of university students. J Infect Dis . 2007;196(8):1128-36. https://doi.org/10.1086/521192
https://doi.org/10.1086/521192... Furthermore, the strongest associations were for having anal sex with other men, as well as for existing sexually transmitted infections.²⁴24. Tejada RA, Vargas KG, Benites-Zapata V, Mezones-Holguín E, Bolaños-Díaz R, Hernández AV. Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis. Salud Publica Mex . 2017;59:84-94. https://doi.org/10.21149/7824
https://doi.org/10.21149/7824... ^,2626. Partridge JM, Hughes JP, Feng Q, Winer RL, Weaver BA, Xi LF, et al. Genital human papillomavirus infection in men: incidence and risk factors in a cohort of university students. J Infect Dis . 2007;196(8):1128-36. https://doi.org/10.1086/521192
https://doi.org/10.1086/521192... ^,2727. Jin F, Prestage GP, Imrie J, Kippax SC, Donovan B, Templeton DJ, et al. Anal sexually transmitted infections and risk of HIV infection in homosexual men. J Acquir Immune Defic Syndr. 2010;53(1):144-9. https://doi.org/10.1097/QAI.0b013e3181b48f33
https://doi.org/10.1097/QAI.0b013e3181b4... Consequently, HPV infection contributes significantly to the burden of disease among men. However, currently no population-based screening methods for detecting HPV-related disease in men have been validated.

Ten years after the introduction of HPV vaccines, there is evidence regarding the main population-level effects in terms of effectiveness. One of the observed impacts is that incident HPV 6/11/16/18 infections have decreased by up to 90% in populations with over 65% coverage with HPV vaccination in women.²⁸28. Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: A systematic review of 10 years of real-world experience. Clin Infect Dis . 2016;63(4):519-27. https://doi.org/10.1093/cid/ciw354
https://doi.org/10.1093/cid/ciw354... Likewise, a decrease of close to 90% in genital warts has been estimated, with a reduction of low-grade cytological abnormalities by nearly 45%, and of high-grade histological lesions by up to 85%.²⁸28. Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: A systematic review of 10 years of real-world experience. Clin Infect Dis . 2016;63(4):519-27. https://doi.org/10.1093/cid/ciw354
https://doi.org/10.1093/cid/ciw354...

In terms of the population-level impact, a herd effect in men has been documented after the introduction of HPV vaccination in women. Heterosexual men residing in contexts with above 50% coverage of HPV vaccination in women show a significant reduction of HPV infections and of ano-genital lesions produced by these infections.²⁹29. Drolet M, Bénard É, Boily MC, Ali H, Baandrup L, Bauer H, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2015;15(5):565-80. https://doi.org/10.1016/S1473-3099(14)71073-4
https://doi.org/10.1016/S1473-3099(14)71... This has been observed in men up to age 40 years. However, the optimum protection at population-level that can be obtained through HPV vaccination has not yet been attained, for lesions caused by HPV infection continue to be a significant cause of morbidity and mortality worldwide.³⁰30. Bray F, Piñeros M. Cancer patterns, trends and projections in Latin America and the Caribbean: a global context. Salud Publica Mex . 2016;58(2):104-17. https://doi.org/10.21149/spm.v58i2.7779
https://doi.org/10.21149/spm.v58i2.7779... This situation implies that the implementation of universal HPV vaccination programs with a high level of population coverage and the inclusion of men in the near future are public health priorities. Also needed are innovative approaches to cervical cancer prevention and control, such as combined screening and vaccination strategies among adult women³¹31. Salmerón J, Torres-Ibarra L, Bosch FX, Cuzick J, Lörincz A, Wheeler CM, et al. HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico. Salud Publica Mex . 2016;58(2):211-9. https://doi.org/10.21149/spm.v58i2.7790
https://doi.org/10.21149/spm.v58i2.7790... as well as the targeting of population groups with the highest incidence of, and mortality due to cervical and other cancers (including anal cancer), and evaluations of the cost-effectiveness of HPV vaccination among adult men.¹²12. Kreuter A, Siorokos C, Oellig F, Silling S, Pfister H, Wieland U. High-grade dysplasia in anogenital warts of HIV-positive men. JAMA Dermatol. 2016;152(11):1225-30. https://doi.org/10.1001/jamadermatol.2016.2503
https://doi.org/10.1001/jamadermatol.201...

Funding

The HIM Study was supported by the National Cancer Institute [R01 CA098803 to ARG] and the National Institute of Allergy and Infectious Disease (R21 AI101417 to AGN), the National Institutes of Health, and the Merck Investigator Initiated Studies Program (grant IISP33707 to A.G.N.). Merck Sharp & Dohme Corp provided financial support for the data analysis.

Acknowledgements

This research was supported in part by research funding from Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp.

We thank the HIM Study teams and participants at Instituto Mexicano del Seguro Social and Instituto Nacional de Salud Pública, Cuernavaca.

References

Publication Dates

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