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Strengthening the case for gender-neutral and the nonavalent HPV vaccine

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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this review is to highlight the benefits of gender-neutral and the nonavalent human papillomavirus vaccination. Human papillomavirus infection is the most commonly sexually transmitted disease and is known to cause several types of cancers, including cervical, vulvar, vaginal, penile, oropharyngeal, anal, and rectal. 5% of cancers every year are attributable to human papillomavirus infection, with cervical cancer the most common and oropharyngeal cancer estimated to surpass the incidence of cervical cancer by 2020.

Methods

PubMed and MEDLINE were searched using the following search terms: [(human papillomavirus OR HPV) AND (vaccine OR vaccination)] AND [(gardasil OR gardasil9 OR cervarix OR quadrivalent OR nonavalent OR ninevalent) OR (gender neutral OR male)].

Results

There are currently three different types of human papillomavirus vaccinations and range in cover from four to nine different strains known to cause human disease. Most countries currently only supply vaccination to females; however, recent data point towards both a personal benefit as well as a cost-effective population-based benefit with gender-neutral vaccination. Data from female vaccination only have shown the vaccine to be effective in preventing premalignant cervical lesions, and are believed to have the same effect for other human papillomavirus cancers. Male vaccination not only provides personal benefit but also has a “herd effect” for females by preventing the propagation of the virus.

Conclusion

Gender-neutral vaccination provides significant cost-effective benefits for preventing human papillomavirus-related diseases, and this effect is further enhanced by the use of the nonavalent vaccine.

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References

  1. Bzhalava D, Guan P, Franceschi S, Dillner J, Clifford G (2013) A systematic review of the prevalence of mucosal and cutaneous human papillomavirus types. Virology 445(1–2):224–231. https://doi.org/10.1016/j.virol.2013.07.015

    Article  CAS  PubMed  Google Scholar 

  2. Viens LJ (2016) Human papillomavirus–associated cancers—United States, 2008–2012. MMWR Morbidity and mortality weekly report 65

  3. Bernard H-U, Burk RD, Chen Z, van Doorslaer K, Hausen Hz, de Villiers E-M (2010) Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 401(1):70–79. https://doi.org/10.1016/j.virol.2010.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schiffman M, Clifford G, Buonaguro FM (2009) Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agents Cancer 4(1):8. https://doi.org/10.1186/1750-9378-4-8

    Article  PubMed  PubMed Central  Google Scholar 

  5. Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, Steinau M, Watson M, Wilkinson EJ, Hopenhayn C, Copeland G, Cozen W, Peters ES, Huang Y, Saber MS, Altekruse S, Goodman MT (2015) US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Inst 107(6):djv086. https://doi.org/10.1093/jnci/djv086

    Article  PubMed  PubMed Central  Google Scholar 

  6. Narisawa-Saito M, Kiyono T (2007) Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci 98(10):1505–1511. https://doi.org/10.1111/j.1349-7006.2007.00546.x

    Article  CAS  PubMed  Google Scholar 

  7. Cancer Trends No 33. HPV-associated cancers (2017). vol 2017. National Cancer Registry Ireland. http://www.ncri.ie/news/article/hpv-associated-cancers-ireland-report-national-cancer-registry

  8. European Public Assessment Report for Gardasil -EMEA/H/C/000703 (2017) European Medicines Agency. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000703/human_med_000805.jsp. Accessed 31 July 2017

  9. European Public Assessment Report for Gardasil 9-EMEA/H/C/003852 (2017) European Medicines Agency. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003852/human_med_001863.jsp&mid=WC0b01ac058001d124. Accessed 31 July 2017

  10. European Public Assessment Report for Cervarix-EMEA/H/C/000721 (2017) European Medicines Agency. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000721/human_med_000694.jsp&mid=WC0b01ac058001d124. Accessed 31 July 2017

  11. Drolet M, Bénard É, Boily MC, Ali H, Baandrup L, Bauer H, Beddows S, Brisson J, Brotherton JML, Cummings T, Donovan B, Fairley CK, Flagg EW, Johnson AM, Kahn JA, Kavanagh K, Kjaer SK, Kliewer EV, Lemieux-Mellouki P, Markowitz L, Mboup A, Mesher D, Niccolai L, Oliphant J, Pollock KG, Soldan K, Sonnenberg P, Tabrizi SN, Tanton C, Brisson M (2015) Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 15(5):565–580. https://doi.org/10.1016/s1473-3099(14)71073-4

    Article  PubMed  PubMed Central  Google Scholar 

  12. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G, Group HPS (2009) Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 374(9686):301–314. https://doi.org/10.1016/S0140-6736(09)61248-4

    Article  CAS  PubMed  Google Scholar 

  13. Malagon T, Drolet M, Boily MC, Franco EL, Jit M, Brisson J, Brisson M (2012) Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12(10):781–789. https://doi.org/10.1016/S1473-3099(12)70187-1

    Article  CAS  PubMed  Google Scholar 

  14. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V (2009) A review of human carcinogens–Part B: biological agents. Lancet Oncol 10(4):321–322

    Article  PubMed  Google Scholar 

  15. Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjose S (2010) Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 202(12):1789–1799. https://doi.org/10.1086/657321

    Article  PubMed  Google Scholar 

  16. Kreimer AR, Bhatia RK, Messeguer AL, Gonzalez P, Herrero R, Giuliano AR (2010) Oral human papillomavirus in healthy individuals: a systematic review of the literature. Sex Transm Dis 37(6):386–391. https://doi.org/10.1097/OLQ.0b013e3181c94a3b

    PubMed  Google Scholar 

  17. Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, Graubard BI, Chaturvedi AK (2012) Prevalence of oral HPV infection in the United States, 2009–2010. JAMA 307(7):693–703. https://doi.org/10.1001/jama.2012.101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, Vignat J, Ferlay J, Bray F, Plummer M, Franceschi S (2012) Global burden of human papillomavirus and related diseases. Vaccine 30 Suppl 5:F12–F23. https://doi.org/10.1016/j.vaccine.2012.07.055

    Article  PubMed  Google Scholar 

  19. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, de Ruiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GA, Lombardi LE, Banjo A, Menendez C, Domingo EJ, Velasco J, Nessa A, Chichareon SC, Qiao YL, Lerma E, Garland SM, Sasagawa T, Ferrera A, Hammouda D, Mariani L, Pelayo A, Steiner I, Oliva E, Meijer CJ, Al-Jassar WF, Cruz E, Wright TC, Puras A, Llave CL, Tzardi M, Agorastos T, Garcia-Barriola V, Clavel C, Ordi J, Andujar M, Castellsague X, Sanchez GI, Nowakowski AM, Bornstein J, Munoz N, Bosch FX, Retrospective International S, Group HPVTTS. (2010) Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 11(11):1048–1056. https://doi.org/10.1016/S1470-2045(10)70230-8

    Article  PubMed  Google Scholar 

  20. Human Papillomavirus (HPV) Vaccine Information (2017) Health service executive. http://www.hse.ie/eng/health/immunisation/pubinfo/schoolprog/hpv/. Accessed 12 Aug 2017

  21. HPV Vaccination Patient Information Leaflet for Men who have Sex with Men (MSM) (2017) Health service executive. http://www.crisispregnancy.ie/wp-content/uploads/2016/09/HPV-Vaccine-Patient-Information-Leaflet-MSM-7Nov2016.pdf. Accessed 12 Aug 2017

  22. Lu B, Kumar A, Castellsague X, Giuliano AR (2011) Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: a systematic review and meta-analysis. BMC Infect Dis 11:13. https://doi.org/10.1186/1471-2334-11-13

    Article  PubMed  PubMed Central  Google Scholar 

  23. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D (2011) Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med 364(5):401–411. https://doi.org/10.1056/NEJMoa0909537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, Jimenez S, Safaeian M, Struijk L, Schussler J, Hildesheim A, Gonzalez P (2016) Multisite HPV16/18 vaccine efficacy against cervical, anal, and oral HPV infection. J Natl Cancer Inst 108 (1). https://doi.org/10.1093/jnci/djv302

  25. Markowitz LE, Tsu V, Deeks SL, Cubie H, Wang SA, Vicari AS, Brotherton JM (2012) Human papillomavirus vaccine introduction—the first five years. Vaccine 30 Suppl 5:F139–F148. https://doi.org/10.1016/j.vaccine.2012.05.039

    Article  PubMed  Google Scholar 

  26. Bonanni P, Cohet C, Kjaer SK, Latham NB, Lambert PH, Reisinger K, Haupt RM (2010) A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD. Vaccine 28(30):4719–4730. https://doi.org/10.1016/j.vaccine.2010.04.070

    Article  PubMed  Google Scholar 

  27. Brotherton JM, Fridman M, May CL, Chappell G, Saville AM, Gertig DM (2011) Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 377(9783):2085–2092. https://doi.org/10.1016/s0140-6736(11)60551-5

    Article  PubMed  Google Scholar 

  28. Korostil IA, Ali H, Guy RJ, Donovan B, Law MG, Regan DG (2013) Near elimination of genital warts in Australia predicted with extension of human papillomavirus vaccination to males. Sex Transm Dis 40(11):833–835. https://doi.org/10.1097/olq.0000000000000030

    Article  PubMed  Google Scholar 

  29. Wangu Z, Hsu KK (2016) Impact of HPV vaccination on anogenital warts and respiratory papillomatosis. Hum Vaccin Immunother 12(6):1357–1362. https://doi.org/10.1080/21645515.2016.1172754

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gillison ML, Alemany L, Snijders PJ, Chaturvedi A, Steinberg BM, Schwartz S, Castellsague X (2012) Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis. Vaccine 30 Suppl 5:F34–F54. https://doi.org/10.1016/j.vaccine.2012.05.070

    Article  PubMed  Google Scholar 

  31. San Giorgi MR, van den Heuvel ER, Tjon Pian Gi RE, Brunings JW, Chirila M, Friedrich G, Golusinski W, Graupp M, Horcasitas Pous RA, Ilmarinen T, Jackowska J, Koelmel JC, Ferran Vila F, Weichbold V, Wierzbicka M, Dikkers FG (2016) Age of onset of recurrent respiratory papillomatosis: a distribution analysis. Clin Otolaryngol 41(5):448–453. https://doi.org/10.1111/coa.12565

    Article  CAS  PubMed  Google Scholar 

  32. Novakovic D, Cheng ATL, Zurynski Y, Booy R, Walker PJ, Berkowitz R, Harrison H, Black R, Perry C, Vijayasekaran S, Wabnitz D, Burns H, Tabrizi SN, Garland SM, Elliott E, Brotherton JML (2017) A prospective study of the incidence of juvenile-onset recurrent respiratory papillomatosis after implementation of a national HPV vaccination program. J Infect Dis. https://doi.org/10.1093/infdis/jix498

    PubMed  Google Scholar 

  33. Young DL, Moore MM, Halstead LA (2015) The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice: Off J Voice Found 29(2):223–229. https://doi.org/10.1016/j.jvoice.2014.08.003

    Article  Google Scholar 

  34. Prue G, Lawler M, Baker P, Warnakulasuriya S (2017) Human papillomavirus (HPV): making the case for ‘Immunisation for All’. Oral Dis 23(6):726–730. https://doi.org/10.1111/odi.12562

    Article  CAS  PubMed  Google Scholar 

  35. Junor EJ, Kerr GR, Brewster DH (2010) Oropharyngeal cancer. Fastest increasing cancer in Scotland, especially in men. BMJ 340:c2512. https://doi.org/10.1136/bmj.c2512

    Article  PubMed  Google Scholar 

  36. Deschler DG, Richmon JD, Khariwala SS, Ferris RL, Wang MB (2014) The “new” head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol Head Neck Surg. 151 (3):375–380. https://doi.org/10.1177/0194599814538605

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301. https://doi.org/10.1200/JCO.2011.36.4596

    Article  PubMed  PubMed Central  Google Scholar 

  38. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (2007) Case–control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356(19):1944–1956. https://doi.org/10.1056/NEJMoa065497

    Article  PubMed  Google Scholar 

  39. Gillison ML, Castellsague X, Chaturvedi A, Goodman MT, Snijders P, Tommasino M, Arbyn M, Franceschi S (2014) Eurogin roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix. Int J Cancer 134(3):497–507. https://doi.org/10.1002/ijc.28201

    Article  CAS  PubMed  Google Scholar 

  40. Du J, Nordfors C, Ahrlund-Richter A, Sobkowiak M, Romanitan M, Nasman A, Andersson S, Ramqvist T, Dalianis T (2012) Prevalence of oral human papillomavirus infection among youth. Swed Emerg Infecti Dis 18(9):1468–1471. https://doi.org/10.3201/eid1809.111731

    Article  Google Scholar 

  41. Handisurya A, Schellenbacher C, Haitel A, Senger T, Kirnbauer R (2016) Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids. Br J Cancer 114(4):409–416. https://doi.org/10.1038/bjc.2015.462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Grun N, Ahrlund-Richter A, Franzen J, Mirzaie L, Marions L, Ramqvist T, Dalianis T (2015) Oral human papillomavirus (HPV) prevalence in youth and cervical HPV prevalence in women attending a youth clinic in Sweden, a follow up-study 2013–2014 after gradual introduction of public HPV vaccination. Inf Dis (London England) 47(1):57–61. https://doi.org/10.3109/00365548.2014.964764

    Google Scholar 

  43. Herrero R, Quint W, Hildesheim A, Gonzalez P, Struijk L, Katki HA, Porras C, Schiffman M, Rodriguez AC, Solomon D, Jimenez S, Schiller JT, Lowy DR, van Doorn LJ, Wacholder S, Kreimer AR (2013) Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PloS One 8(7):e68329. https://doi.org/10.1371/journal.pone.0068329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. VFC Program. Centers for disease control and prevention. https://www.cdc.gov/features/vfcprogram/. Accessed 12 Aug 2016

  45. Takes RP, Wierzbicka M, D’Souza G, Jackowska J, Silver CE, Rodrigo JP, Dikkers FG, Olsen KD, Rinaldo A, Brakenhoff RH, Ferlito A (2015) HPV vaccination to prevent oropharyngeal carcinoma: What can be learned from anogenital vaccination programs? Oral oncology 51(12):1057–1060. https://doi.org/10.1016/j.oraloncology.2015.10.011

    Article  PubMed  Google Scholar 

  46. HPV Vaccine Coverage Maps-Inforgraphic (2016) Centers for disease control and prevention. https://www.cdc.gov/hpv/infographics/vacc-coverage.html. Accessed 12 Aug 2017

  47. HPV Vaccine Uptake in Ireland: 2015/2016 (2017) Health service executive. https://www.hpsc.ie/a-z/vaccinepreventable/vaccination/immunisationuptakestatistics/hpvimmunisationuptakestatistics/File,16039,en.pdf. Accessed 12 Aug 2017

  48. Bottiger M, Forsgren M (1997) Twenty years’ experience of rubella vaccination in Sweden: 10 years of selective vaccination (of 12-year-old girls and of women postpartum) and 13 years of a general two-dose vaccination. Vaccine 15(14):1538–1544

    Article  CAS  PubMed  Google Scholar 

  49. Bogaards JA, Wallinga J, Brakenhoff RH, Meijer CJ, Berkhof J (2015) Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis. Bmj 350:h2016. https://doi.org/10.1136/bmj.h2016

    Article  PubMed  PubMed Central  Google Scholar 

  50. Graham DM, Isaranuwatchai W, Habbous S, de Oliveira C, Liu G, Siu LL, Hoch JS (2015) A cost-effectiveness analysis of human papillomavirus vaccination of boys for the prevention of oropharyngeal cancer. Cancer 121(11):1785–1792. https://doi.org/10.1002/cncr.29111

    Article  PubMed  Google Scholar 

  51. Marty R, Roze S, Bresse X, Largeron N, Smith-Palmer J (2013) Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe. BMC Cancer 13:10. https://doi.org/10.1186/1471-2407-13-10

    Article  PubMed  PubMed Central  Google Scholar 

  52. Monsonego J, Breugelmans JG, Bouee S, Lafuma A, Benard S, Remy V (2007) [Anogenital warts incidence, medical management and costs in women consulting gynaecologists in France]. Gynecol Obstet Fertil 35(2):107–113. https://doi.org/10.1016/j.gyobfe.2006.12.010

    Article  CAS  PubMed  Google Scholar 

  53. Hartwig S, St Guily JL, Dominiak-Felden G, Alemany L, de Sanjose S (2017) Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe. Infect Agent Cancer 12:19. https://doi.org/10.1186/s13027-017-0129-6

    Article  PubMed  PubMed Central  Google Scholar 

  54. Statistics by cancer type (2017) Cancer research UK. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type. Accessed 15 Aug 2017

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Hintze, J.M., O’Neill, J.P. Strengthening the case for gender-neutral and the nonavalent HPV vaccine. Eur Arch Otorhinolaryngol 275, 857–865 (2018). https://doi.org/10.1007/s00405-018-4866-y

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