HPV Vaccine

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
  • Virus-like particles
  • Recombinant protein expression
  • Immunization against an epithelial infection
  • Prevention of papillomavirus-induced disease

Keywords: HPV; vaccine; cervical cancer; genital warts

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.
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 References
    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.
    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.
    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.
    book Howley PM and Lowy DR (2007) "Papillomaviruses". In: Knipe DM and Howley PM (eds) Fields Virology, 5th ed, pp. 2300–2354. Philadelphia: Lippincott, Williams and Wilkins.
    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 USA 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. Epidemiological Reviews 10: 122–163.
    Lacey CJ (2005) Therapy for genital human papillomavirus related disease. Journal of Clinical Virology 32(suppl 1): S82–S90.
    Lacey CJN, Lowndes CM and Shah K (2006) Burden and management of non-cancerous HPV related conditions: HPV-6/11 disease. Vaccine 24S3: S3/35–S3/41.
    Munoz N, Bosch FX, Castellsague X et al. (2004) Against which HPV vaccine types shall we vaccinate and screen? International Journal of Cancer 111(2): 278–285.
    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.
    Parkin DM and Bray F (2006) The burden of HPV-related cancers. Vaccine 24S3: S3/11–S3/25.
    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.
    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.
    Schiller JT, Castellsagué X, Villa LL and Hildesheim A (2008) An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 26(suppl 10): K53–K61.
    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.
    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 USA 92: 11553–11557.
    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
    other Castellsague X, de Sanjose S, Aguado T et al. (eds) (2007) HPV and cervical cancer in the world: 2007 report. Vaccine 25 (suppl 3): C1–C230.
    other 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.
    Markowitz LE, Dunn EF and Saraiya M. (2007) Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP), vol. 56(RR02), pp. 1–24. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm
    book Stern PL and Kitchener HC (eds) (2008) Vaccines for the Prevention of Cervical Cancer (Oxford Oncology Library), Paperback: 170pp. Oxford: Oxford University Press.
    ePath WHO/ICO (2009) Information Centre on Human Papilloma Virus (HPV) and Cervical Cancer; http://www.who.int/hpvcentre/en/
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Inglis, Stephen(Dec 2009) HPV Vaccine. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021551]