HPV Vaccines

Abstract

The discovery in the early 1970s that cervical cancer was caused by infection with human papillomavirus (HPV) stimulated a highly successful vaccine development programme based on the use of recombinant deoxyribonucleic acid (DNA) technology to produce virus proteins in a form that can stimulate powerful and long‐lasting antibody responses. The vaccines have been designed as combinations to target the HPV virus types that are responsible for most human disease. Clinical trials have shown that it is possible to prevent both genital warts and the early stages of cervical cancer through vaccination and this has led to licensure and use of HPV vaccines in many countries throughout the world. Progression from initial virus infection to development of invasive cancer is often very slow, however, and so it will be many years before the impact of the vaccine on the overall disease burden is fully understood.

Key Concepts

  • Vaccine development for HPV has been complex but highly successful. Successful vaccines were made by recombinant protein expression to produce virus‐like particles (VLPs).
  • Prevention of papillomavirus‐induced disease requires neutralising antibodies at the mucosal site of infection.
  • The main public health priority was to achieve high coverage in vaccinating women with the aim to prevent cervical cancer.
  • Prophylactic HPV vaccine efficacy has been remarkably high.
  • Some cross‐protection is observed between different vaccine types.
  • HPV vaccines have been implemented in populations of young women widely around the world.
  • Access to affordable HPV vaccines in poor countries is a key goal but remains a challenge.
  • The scope of HPV vaccination extends to the prevention of non‐cervical HPV infections and related diseases in both females and males.

Keywords: HPV; vaccine; cervical cancer; genital warts; vaccine trials; multivalent vaccines; immunisation

Figure 1. Principal disease targets for HPV vaccination. (a) Courtesy of Professor Margaret Stanley and (b) Courtesy of Professor Charles Lacey.
Figure 2. Histological changes associated with progression to cervical cancer. Courtesy of Professor Margaret Stanley.
Figure 3. Electron micrographs of naturally occurring virus and virus‐like particles produced by recombinant DNA expression.
close

References

ATAG (2013) Australian Technical Advisory Group on Immunisation. The Australian Immunisation Handbook, 10th edn. Australian Government Department of Health: Canberra.

Bosch FX, Broker TR, Forman D, et al. (2013) Comprehensive control of human papillomavirus infections and related diseases. Vaccine 31(Supplement 7(0)): H1–H31.

Breitburd F, Kirnbauer R, Hubbert NL, et al. (1995) Immunization with virus‐like particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. Journal of Virology 69: 3959–3963.

Bruni L, Barrionuevo‐Rosas L, Serrano B, et al. (2014) ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in World. Summary Report 2014‐04‐08. Available at: http://www.hpvcentre.net

CDC (2014) US Centers for Disease Control. Human Papillomavirus Vaccination: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recommendations and Reports, vol. 63/No. RR–5. Available at http://www.cdc.gov/mmwr/pdf/rr/rr6305.pdf

Chan SY, Delius H and Halpern AL (1995) Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny and taxonomy. Journal of Virology 69: 3074–3083.

CIC (2014) Canadian Immunization Committee. Recommendations for Human Papillomavirus Immunization Programs. Available at http://publications.gc.ca/pub?id=464264&sl=0

de Sanjose S, Quint WGV, Alemany L, et al. (2010) Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross‐sectional worldwide study. The Lancet Oncology 11 (11): 1048–1056.

Derkay CS (1995) Task force on recurrent respiratory papillomas. A preliminary report. Archives of Otolaryngology—Head and Neck Surgery 121 (12): 1386–1391.

FUTURE II Study Group (2007a) Quadrivalent vaccine against human papillomavirus to prevent high‐grade cervical lesions. New England Journal of Medicine 356 (19): 1915–1927.

FUTURE II Study Group (2007b) Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. Journal of Infectious Disease 196: 1438–1446.

Garland SM, Hernandez‐Avila M, Wheeler CM, et al. (2007) Females united to unilaterally reduce endo/ectocervical disease (FUTURE) I investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. New England Journal of Medicine 356 (19): 1928–1943.

Herrero R, Quint W, Hildesheim A, et al. (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.

Herrero R, Wacholder S, Rodriguez AC, et al. (2011) Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community‐based randomized clinical trial in Guanacaste, Costa Rica. Cancer Discovery 1 (5): 408–419.

Howley PM and Lowy DR (2007) Papillomaviruses. In: Knipe DM and Howley PM, (eds). Fields Virology, 5th edn., pp. 2300–2354. Philadelphia: Lippincott, Williams and Wilkins.

IARC (2012a). GLOBOCAN 2012: Cervical Cancer Estimated Incidence, Mortality and Prevalence Worldwide. Available at http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx?cancer=cervix

IARC (2012b) A review of human carcinogens. Biological agents. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 100 (Pt B): 1–441.

IARC (2014). IARC Working Group Reports; 7, Primary End‐points for Prophylactic HPV Vaccine Trials. Available at http://www.iarc.fr/en/publications/pdfs‐online/wrk/wrk7/Prophylactic_HPV_VaccineTrials.pdf

Joura E. on behalf of the V503‐001 Study Team (2013). Efficacy and Immunogenicity of a Novel 9‐Valent HPV L1 Virus‐Like Particle Vaccine in 16‐ to 26‐Year‐Old Women. Abstract SS 8–4, p. 102. EUROGIN Congress 2013, Florence, Italy.

Kirnbauer R, Booy F, Cheng N, Lowy DR and Schiller JT (1992) Papillomavirus L1 major capsid protein self‐assembles into virus‐like particles that are highly immunogenic. Proceedings of the National Academy of Sciences of the United States of America 89: 12180–12184.

Kirnbauer R, Chandrachud L, O'Neil B, et al. (1996) Virus‐like particles of Bovine Papillomavirus type 4 in prophylactic and therapeutic immunization. Virology 219: 37–44.

Koutsky LA, Galloway DA and Holmes KK (1988) Epidemiology of genital human papillomavirus infection. Epidemiologic Reviews 10: 122–163.

Lacey CJ (2005) Therapy for genital human papillomavirus related disease. Journal of Clinical Virology 32 (suppl 1): S82–S90.

Lehtinen M, Paavonen J, Wheeler CM, et al. (2012) 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 Oncology 13 (1): 89–99.

Luna J, Plata M, Gonzalez M, et al. (2013) Long‐term follow‐up observation of the safety, immunogenicity, and effectiveness of Gardasil in adult women. PLoS One 8 (12): e83431.

Paavonen J, Jenkins D, Bosch FX, et al. (2007) Efficacy of a prophylactic adjuvanted bivalent L1 virus‐like‐particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double‐blind, randomised controlled trial. Lancet 370 (9596): 1414.

Pastrana DV, Buck CB, Pang YY, et al. (2004) Reactivity of human sera in a sensitive, high‐throughput pseudovirus‐based papillomavirus neutralization assay for HPV16 and HPV18. Virology 321 (2): 205–216.

Read TRH, Hocking JS, Chen MY, et al. (2011) The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sexually Transmitted Infections 87 (7): 544–547.

Roden RBS, Greenstone HL, Kirnbauer R, et al. (1996) In vitro generation and type‐specific neutralization of a human papillomavirus type 16 virion pseudotype. Journal of Virology 70: 5875–5883.

Romanowski B, de Borba PC, Naud PS, et al. (2009) Sustained efficacy and immunogenicity of the human papillomavirus (HPV)‐16/18 AS04‐adjuvanted vaccine: analysis of a randomised placebo‐controlled trial up to 6.4 years. Lancet 374 (9706): 1975–1985.

Roteli‐Martins CM, Naud P, De Borba P, et al. (2012) Sustained immunogenicity and efficacy of the HPV‐16/18 AS04‐adjuvanted vaccine: up to 8.4 years of follow‐up. Human Vaccines & Immunotherapeutics 8 (3): 390–397.

Smith LH, Foster C, Hitchcock ME, et al. (1995) Titration of HPV‐11 infectivity and antibody neutralization can be measured in vitro. Journal of Investigative Dermatology 105: 438–444.

Stanley M (2014) HPV vaccination in boys and men. Human Vaccines & Immunotherapeutics 10 (7): 1–3.

Stern PL (2005) Immune control of human papillomavirus (HPV) associated anogenital disease and potential for vaccination. Journal of Clinical Virology 32 (suppl 1): S72–S81.

Suzich JA, Ghim S, Palmer‐Hill FJ, et al. (1995) Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proceedings of the National Academy of Sciences of the United States of America 92: 11553–11557.

Wheeler CM, Castellsague X, Garland SM, et al. (2012) Cross‐protective efficacy of HPV‐16/18 AS04‐adjuvanted vaccine against cervical infection and precancer caused by non‐vaccine oncogenic HPV types: 4‐year end‐of‐study analysis of the randomised, double‐blind PATRICIA trial. Lancet Oncology 13 (1): 100–110.

Wigle J, Coast E and Watson‐Jones D (2013) Human papillomavirus (HPV) vaccine implementation in low and middle‐income countries (LMICs): Health system experiences and prospect. Vaccine 31 (37): 3811–3817.

WHO (2014). Human papilloma virus vaccines. Weekly Epidemiological Record 89(21): 229–230. Available at: http://www.who.int/wer/2014/wer8921.pdf?ua=1

Zhou J, Sun XY, Stenzel DJ and Frazer IH (1991) Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion‐like particles. Virology 185: 251–257.

Zimet GD, Liddon N, Rosenthal SL, Lazcano‐Ponce E and Allen B (2006) Psychosocial aspects of vaccine acceptability. Vaccine 24S3: S3/201–S3/209.

Zur Hausen H, Meinhof W, Scheiber W and Bornkamm GW (1974) Attempts to detect virus specific DNA in human tumours. I Nucleic acid hybridizations with complementary RNA of human wart virus. International Journal of Cancer 13 (5): 650–656.

Further Reading

ECDC (2012) European Centre for Disease Prevention and Control. Introduction of HPV vaccines in EU countries – an update. Stockholm. Available at http://www.ecdc.europa.eu/en/publications/_layouts/forms/Publication_DispForm.aspx?List=4f55ad51‐4aed‐4d32‐b960‐af70113dbb90&ID=677. This is a guidance document for policymakers in Europe.

Franco EL and Drummond MF (eds) (2008) Health economics of HPV vaccination for cervical cancer prevention: historical developments and practical applications. Vaccine 26 (suppl 5): F1–F58.

ICO Information Centre on Human Papilloma Virus (HPV) and Cervical Cancer. http://www.who.int/hpvcentre/en/

Stern PL and Kitchener HC (eds) (2008) Vaccines for the Prevention of Cervical Cancer (Oxford Oncology Library), Paperback, pp. 1–170. Oxford: Oxford University Press.

Vaccine (2013) Dec 31 Suppl 7. Several review articles on HPV vaccines and their implementation.

WHO HPV Vaccine Introduction Clearing House; http://www.who.int/immunization/hpv/en/

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wilkinson, Dianna E, and Inglis, Stephen(Jan 2015) HPV Vaccines. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021551.pub2]