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Does HPV vaccination prevent cervical carcinoma?


It is now 12 years ago that the first girls were vaccinated against human papilloma virus (HPV) under the Dutch government’s national vaccination programme, and by now more research has been undertaken into the efficacy of HPV vaccination. Both the vaccine against two high-risk HPV types (bivalent vaccine) and that against four high-risk HPV types (quadrivalent vaccines) appear to be effective for the prevention of precursor lesions of cervical carcinoma. It is not yet clear whether a vaccine against a total of nine high-risk HPV types (nonavalent vaccine) offers any added value compared to the bivalent and quadrivalent vaccines. The vaccines appear to be especially effective when administered before the infection with HPV has occurred. Observational studies concerning direct efficacy and population effects corroborate the evidence from the efficacy studies. No difference in the incidence of mild or serious adverse events has been found between HPV vaccination and placebo.

  • Randomised research and observational studies have yielded solid evidence for the efficacy of both the bivalent and quadrivalent vaccines in preventing precursor lesions of cervical carcinoma.
  • No conclusions can as yet be drawn regarding the hard endpoint of cervical carcinoma, as this can as yet not be adequately assessed, due to the slow development of these carcinomas.
  • Since the studies have mostly been funded by the industry, there is a need for more publicly funded research.
  • The adverse effects of the HPV vaccine and the vaccination differ little from those of other vaccinations. One study has concluded that migraine might be more frequent after HPV vaccination, but this requires further investigation.

  1. Akbarali S, de Vries Tj. Vaccinatie tegen humaan papillomavirus. Gebu. 2016;50(10):112-122.
  2. World Health Oganization. webpagina Cervical Cancer. Available from: www.who.int/health-topics/cervical-cancer#tab=tab_1. Accessed 03-03-2021.
  3. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018 May 9;5(5):CD009069. doi: 10.1002/14651858.CD009069.pub3. 
  4. European Medicines Agency. Productinformatie Cervarix®. Available from: https://www.ema.europa.eu/en/documents/product-information/cervarix-epar-product-information_nl.pdf. Accessed 03-03-2021.
  5. European Medicines Agency. Productinformatie Gardasil®. Available from: https://www.ema.europa.eu/en/documents/product-information/gardasil-epar-product-information_nl.pdf. Accessed 03-03-2021.
  6. European Medicines Agency. Productinformatie Gardasil 9®. Available from: https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-product-information_nl.pdf. Accessed 03-03-2021.
  7. NVOG, NVVP, NVVM. Richtlijn Cervicale intra-epitheliale neoplasie (CIN). Bijlage classificatie CIN. 12 november 2015. Available from: https://richtlijnendatabase.nl/richtlijn/cin_ais_en_vain/algemeen.html. Accessed 09-03-2021.
  8. Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsagué X, et al. HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan;13(1):89-99. doi: 10.1016/S1470-2045(11)70286-8. Erratum in: Lancet Oncol. 2012 Jan;13(1):e1. 
  9. Bijl D. Vaccinatie tegen Humaan papillomavirus. Gebu. 2009;43(7):69-76.
  10. Porras C, Tsang SH, Herrero R, Guillén D, Darragh TM, Stoler MH, et al. Costa Rica Vaccine Trial Group. Efficacy of the bivalent HPV vaccine against HPV 16/18-associated precancer: long-term follow-up results from the Costa Rica Vaccine Trial. Lancet Oncol. 2020 Dec;21(12):1643-1652. doi: 10.1016/S1470-2045(20)30524-6. 
  11. Herrero R, Hildesheim A, Rodríguez AC, Wacholder S, Bratti C, Solomon D, et al. Costa Rica Vaccine Trial (CVT) Group. Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica. Vaccine. 2008 Sep 2;26(37):4795-808. doi: 10.1016/j.vaccine.2008.07.002.
  12. Herrero R, Wacholder S, Rodríguez AC, Solomon D, González P, Kreimer AR, et al. Costa Rica Vaccine Trial Group. Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica. Cancer Discov. 2011 Oct;1(5):408-19. doi: 10.1158/2159-8290.CD-11-0131.
  13. Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet. 2017 Nov 11;390(10108):2143-2159. doi: 10.1016/S0140-6736(17)31821-4.
  14. Rijksinstituut voor Volksgezondheid en Milieu. Wijziging HPV-vaccinatieschema: 1 prik minder. Bulletin. 26-02-2014. Available from: https://www.rivm.nl/wijziging-hpv-vaccinatieschema-1-prik-minder.
  15. Whitworth HS, Gallagher KE, Howard N, Mounier-Jack S, Mbwanji G, Kreimer AR, et al. Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: A systematic review of evidence from clinical trials. Vaccine. 2020 Feb 5;38(6):1302-1314. doi: 10.1016/j.vaccine.2019.12.017. 
  16. Gezondheidsraad. Vaccinatie tegen HPV. Advies aan de staatssecretaris van Volksgezondheid, Welzijn en Sport. Den Haag: Gezondheidsraad, 19 juni 2019. Publicatienr. 2019/09, Available from: https://www.gezondheidsraad.nl/documenten/adviezen/2019/06/19/vaccinatie-tegen-hpv. Accessed 09-03-2021.
  17. Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020 Oct 1;383(14):1340-1348. doi: 10.1056/NEJMoa1917338.
  18. Donken R, King AJ, Bogaards JA, Woestenberg PJ, Meijer CJLM, de Melker HE. High Effectiveness of the Bivalent Human Papillomavirus (HPV) Vaccine Against Incident and Persistent HPV Infections up to 6 Years After Vaccination in Young Dutch Women. J Infect Dis. 2018 Apr 23;217(10):1579-1589. doi: 10.1093/infdis/jiy067.
  19. Woestenberg PJ, King AJ, van Benthem BHB, Donken R, Leussink S, van der Klis FRM, et al. Medical Microbiological Laboratories and the Public Health Services. Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors. J Infect Dis. 2018 Jan 4;217(2):213-222. doi: 10.1093/infdis/jix582.
  20. Drolet M, Bénard É, Pérez N, Brisson M; HPV Vaccination Impact Study Group. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019 Aug 10;394(10197):497-509. doi: 10.1016/S0140-6736(19)30298-3.
  21. Palmer T, Wallace L, Pollock KG, Cuschieri K, Robertson C, Kavanagh K, et al. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ. 2019 Apr 3;365:l1161. doi: 10.1136/bmj.l1161.
  22. Yoon D, Lee JH, Lee H, Shin JY. Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study. BMJ. 2021 Jan 29;372:m4931. doi: 10.1136/bmj.m4931.
  23. Bijwerkingencentrum Lareb. Long-lasting adverse events following immunization with Cervarix®. December 2015. Available from: https://databankws.lareb.nl/Downloads/Lareb_rapport_HPV_dec15_03.pdf. Accessed 09-03-2021. 
  24. Bijwerkingencentrum Lareb. Long-lasting adverse events following immunization with Cervarix®. Update 2016. Available from: https://www.lareb.nl/media/n0kp5v00/cervarix_31102016.pdf. Accessed 09-03-2021.
  25. Bijwerkingencentrum Lareb. Available from: https://www.lareb.nl/nl-nl/databank/result?drug=CERVARIX%20%28PAPILLOMAVIRUSVACCIN%29&formGroup=Suspensie%20voor%20injectie&atc=J07BM02. Accessed 30-12-2020.
  26. Schurink-Van't Klooster TM, Kemmeren JM, van der Maas NAT, van de Putte EM, Ter Wolbeek M, Nijhof SL, et al. No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls. Vaccine. 2018 Oct 29;36(45):6796-6802. doi: 10.1016/j.vaccine.2018.09.019. 
  27. Feiring B, Laake I, Bakken IJ, Greve-Isdahl M, Wyller VB, Håberg SE, et al. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine. 2017 Jul 24;35(33):4203-4212. doi: 10.1016/j.vaccine.2017.06.031.
  28. European Medicines Agency. Persbericht EMA. HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS. 20 november 2015. Available from: https://www.ema.europa.eu/en/documents/press-release/hpv-vaccines-ema-confirms-evidence-does-not-support-they-cause-crps-pots_en.pdf. Accessed 20-05-2021.
  29. Europese Ombudsman. Decision in case 1475/2016/JAS on the European Medicines Agency’s handling of the referral procedure relating to human papillomavirus (HPV) vaccines. Available from: https://www.ombudsman.europa.eu/nl/decision/en/84736. Accessed 09-03-2021.

Authors

  • MariĆ«lle van Avendonk
  • Marielle A.E. Nieuwhof, pharmacist
  • Frans M. Helmerhorst, prof. dr