BioDrugs

, Volume 25, Issue 5, pp 339–343

Spotlight on Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (Gardasil®) in the Prevention of Premalignant Genital Lesions, Genital Cancer, and Genital Warts in Women

Adis Spotlight

Abstract

Quadrivalent human papilloma virus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil®; Silgard®) is composed of virus-like particles (VLPs) formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16, and 18. The VLPs are noninfectious, containing no DNA, and are highly immunogenic, inducing high levels of neutralizing antibodies against the particular HPV types when administered to animals or humans. Quadrivalent HPV vaccine is indicated for use from the age of 9 years for the prevention of premalignant genital lesions (cervical, vulvar, and vaginal), cervical cancer, and external genital warts (condyloma acuminata) causally related to certain oncogenic or specific HPV types.

In placebo-controlled clinical trials, quadrivalent HPV vaccine administered as three doses over 6 months provided high-level protection against infection or disease caused by the vaccine HPV types over 2–4 years of follow-up in females aged 15–45 years who were naive to the vaccine HPV types. A degree of cross-protection against certain other non-vaccine high-risk HPV types was also observed. The vaccine is not effective against current infection with a vaccine HPV type. Girls or women with current infection with one or more of the vaccine HPV types gained protection from infection or disease caused by the remaining vaccine HPV types and they were also protected against reinfection with the same HPV type after clearance of an infection caused by a vaccine HPV type. High seroconversion rates and high levels of anti-HPV antibodies were observed in all vaccinated individuals of all age ranges from 9 to 45 years. No correlation was found between antibody levels and protective efficacy of the vaccine. Rechallenge with quadrivalent HPV vaccine produced a potent anamnestic humoral immune response. The vaccine is generally well tolerated and is projected to be cost effective in most pharmacoeconomic models. Therefore, quadrivalent HPV vaccine offers an effective means, in combination with screening programs, to substantially reduce the burden of HPV-related precancerous lesions and cancer, particularly cervical cancer, as well as anogenital warts.

References

  1. 1.
    European Medicines Agency. Gardasil (human papillomavirus vaccine [types 6, 11, 16, 18] recombinant, absorbed): summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/humandocs/Humans/EPAR/gardasil/gardasil.htm [Accessed 2010 Oct 11]
  2. 2.
    Merck & Co. Gardasil [human papillomavirus quadrivalent (types 6,11,16 and 18) vaccine, recombinant]: US prescribing information [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf [Accessed 2010 Nov 9]
  3. 3.
    Stanley M. Prophylactic HPV vaccines. J Clin Pathol 2007 Sep; 60 (9): 961–5PubMedCrossRefGoogle Scholar
  4. 4.
    Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006 Aug 31; 24Suppl. 3: S3–11–25PubMedGoogle Scholar
  5. 5.
    Lacey CJN, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 2006 Aug 31; 24Suppl. 3: S3–35–41PubMedGoogle Scholar
  6. 6.
    Garland SM, Steben M, Sings HL, et al. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6,11,16, and 18) vaccine. J Infect Dis 2009 Mar 15; 199 (6): 805–14PubMedCrossRefGoogle Scholar
  7. 7.
    Einstein MH, Baron M, Levin MJ, et al. Comparison of the immunogenicity and safety of Cervarix™ and Gardasil® human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Hum Vaccin 2009 Oct; 5 (10): 705–19PubMedCrossRefGoogle Scholar
  8. 8.
    Joura EA, Kjaer SK, Wheeler CM, et al. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine 2008 Dec 9; 26 (52): 6844–51PubMedCrossRefGoogle Scholar
  9. 9.
    Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005 May; 6 (5): 271–8PubMedCrossRefGoogle Scholar
  10. 10.
    Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 2006 Jul 7; 24 (27-28): 5571–83PubMedCrossRefGoogle Scholar
  11. 11.
    Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007 May 10; 356 (19): 1928–43PubMedCrossRefGoogle Scholar
  12. 12.
    FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007 May 10; 356 (19): 1915–27CrossRefGoogle Scholar
  13. 13.
    Olsson SE, Villa LL, Costa RL, et al. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine 2007 Jun 21; 25 (26): 4931–9PubMedCrossRefGoogle Scholar
  14. 14.
    Muñoz N, Manalastas Jr R, Pitisuttithum P, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. Lancet 2009 Jun 6; 373 (9679): 1949–57PubMedCrossRefGoogle Scholar
  15. 15.
    Garland SM, Steben M, Hernandez-Avila M, et al. Noninferiority of antibody response to human papillomavirus type 16 in subjects vaccinated with monovalent and quadrivalent L1 virus-like particle vaccines. Clin Vaccine Immunol 2007 Jun; 14 (6): 792–5PubMedCrossRefGoogle Scholar
  16. 16.
    Smith JF, Brownlow M, Brown M, et al. Antibodies from women immunized with Gardasil® cross-neutralize HPV 45 pseudovirions. Hum Vaccin 2007 Jul 31; 3 (4): 109–15PubMedCrossRefGoogle Scholar
  17. 17.
    Reisinger KS, Block SL, Lazcano-Ponce E, et al. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J 2007 Mar; 26 (3): 201–9PubMedCrossRefGoogle Scholar
  18. 18.
    Block SL, Nolan T, Sattler C, et al. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics 2006 Nov; 118 (5): 2135–45PubMedCrossRefGoogle Scholar
  19. 19.
    Wheeler CM, Bautista OM, Tomassini JE, et al. Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/1 1/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines. Vaccine 2008 Jan 30; 26 (5): 686–96PubMedCrossRefGoogle Scholar
  20. 20.
    Vesikari T, Van Damme P, Lindblad N, et al. An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of quadrivalent human papillomavirus (types 6/11/16/18) vaccine given concomitantly with diphtheria, tetanus, pertussis, and poliomyelitis vaccine in healthy adolescents 11 to 17 years of age. Pediatr Infect Dis J 2010 Apr; 29 (4): 314–8PubMedGoogle Scholar
  21. 21.
    Reisinger KS, Block SL, Collins-Ogle M, et al. Safety, tolerability, and immunogenicity of Gardasil given concomitantly with Menactra and Adacel. Pediatrics 2010 Jun; 125 (6): 1142–51PubMedCrossRefGoogle Scholar
  22. 22.
    Arguedas A, Soley C, Loaiza C, et al. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines. Vaccine 2010 Apr 19; 28 (18): 3171–9PubMedCrossRefGoogle Scholar
  23. 23.
    Kjaer SK, Sigurdsson K, Iversen OE, et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res (Phila Pa) 2009 Oct; 2 (10): 868–78CrossRefGoogle Scholar
  24. 24.
    Ault KA, FUTURE II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet 2007 Jun 2; 369 (9576): 1861–8PubMedCrossRefGoogle Scholar
  25. 25.
    Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006 Dec 4; 95 (11): 1459–66PubMedCrossRefGoogle Scholar
  26. 26.
    Olsson SE, Kjaer SK, Sigurdsson K, et al. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Hum Vaccin 2009 Oct 14; 5 (10): 696–704PubMedCrossRefGoogle Scholar
  27. 27.
    FUTURE II Study Group. Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis 2007 Nov 15; 196 (10): 1438–46CrossRefGoogle Scholar
  28. 28.
    Brown DR, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6,11,16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16–26 years. J Infect Dis 2009 Apr 1; 199 (7): 926–35PubMedCrossRefGoogle Scholar
  29. 29.
    Wheeler CM, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16–26 years. J Infect Dis 2009 Apr 1; 199 (7): 936–44PubMedCrossRefGoogle Scholar
  30. 30.
    Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011 Jan; 11 (1): 39–44PubMedCrossRefGoogle Scholar
  31. 31.
    Block SL, Brown DR, Chatterjee A, et al. Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6,11,16, and 18) L1 virus-like particle vaccine. Pediatr Infect Dis J 2010 Feb; 29 (2): 95–101PubMedCrossRefGoogle Scholar
  32. 32.
    Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 2009 Aug 19; 302 (7): 750–7PubMedCrossRefGoogle Scholar
  33. 33.
    Annemans L, Rémy V, Oyee J, et al. Cost-effectiveness evaluation of a quadrivalent human papillomavirus vaccine in Belgium. Pharmacoeconomics 2009; 27 (3): 231–45PubMedCrossRefGoogle Scholar
  34. 34.
    Kulasingam SL, Benard S, Barnabas RV, et al. Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: a cost-effectiveness analysis. Cost Eff Resour Alloc 2008; 6: 4PubMedCrossRefGoogle Scholar
  35. 35.
    Bergeron C, Largeron N, McAllister R, et al. Cost-effectiveness analysis of the introduction of a quadrivalent human papillomavirus vaccine in France. Int J Technol Assess Health Care 2008 Winter; 24 (1): 10–9PubMedCrossRefGoogle Scholar
  36. 36.
    Mennini FS, Rossi PG, Palazzo F, et al. Health and economic impact associated with a quadrivalent HPV vaccine in Italy. Gynecol Oncol 2009 Feb; 112 (2): 370–6PubMedCrossRefGoogle Scholar
  37. 37.
    Szucs TD, Largeron N, Dedes KJ, et al. Cost-effectiveness analysis of adding a quadrivalent HPV vaccine to the cervical cancer screening programme in Switzerland. Curr Med Res Opin 2008; 24 (5): 1473–83PubMedCrossRefGoogle Scholar
  38. 38.
    Brisson M, Van de Velde N, De Wals P, et al. The potential cost-effectiveness of prophylactic human papillomavirus vaccines in Canada. Vaccine 2007 Jul 20; 25 (29): 5399–408PubMedCrossRefGoogle Scholar
  39. 39.
    Chesson HW, Ekwueme DU, Saraiya M, et al. Cost-effectiveness of human papillomavirus vaccination in the United States. Emerg Infect Dis 2008 Feb; 14 (2): 244–51PubMedCrossRefGoogle Scholar
  40. 40.
    Dee A, Howell F. A cost-utility analysis of adding a bivalent or quadrivalent HPV vaccine to the Irish cervical screening programme. Eur J Public Health 2010 Apr; 20 (2): 213–9PubMedCrossRefGoogle Scholar
  41. 41.
    Dasbach EJ, Largeron N, Elbasha EH. Assessment of the cost-effectiveness of a quadrivalent HPV vaccine in Norway using a dynamic transmission model. Expert Rev Pharmacoecon Outcomes Res 2008 Oct; 8 (5): 491–500PubMedCrossRefGoogle Scholar
  42. 42.
    Dasbach EJ, Insinga RP, Elbasha EH. The epidemiological and economic impact of a quadrivalent human papillomavirus vaccine (6/11/16/18) in the UK. BJOG 2008 Jul; 115 (8): 947–56PubMedCrossRefGoogle Scholar
  43. 43.
    Insinga RP, Dasbach EJ, Elbasha EH, et al. Cost-effectiveness of quadrivalent human papillomavirus (HPV) vaccination in Mexico: a transmission dynamic model-based evaluation. Vaccine 2007 Dec 21; 26 (1): 128–39PubMedCrossRefGoogle Scholar
  44. 44.
    Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus vaccination in the United Kingdom. BMJ 2008 Aug 9; 337 (7665): 331–5Google Scholar
  45. 45.
    Elbasha EH, Dasbach EJ, Insinga RP. Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis 2007 Jan; 13 (1): 28–41PubMedCrossRefGoogle Scholar
  46. 46.
    Dasbach EJ, Nagy L, Brandtmüller A, et al. The cost effectiveness of a quadrivalent human papillomavirus vaccine (6/11/16/18) in Hungary. J Med Econ 2010 Mar; 13 (1): 110–8PubMedCrossRefGoogle Scholar
  47. 47.
    Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med 2008 Aug 21; 359 (8): 821–32PubMedCrossRefGoogle Scholar
  48. 48.
    Olsen J, Jepsen MR. Human papillomavirus transmission and cost-effectiveness of introducing quadrivalent HPV vaccination in Denmark. Int J Technol Assess Health Care 2010 Apr; 26 (2): 183–91PubMedCrossRefGoogle Scholar
  49. 49.
    McCormack PL, Joura EA. Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil®): a review of its use in the prevention of premalignant genital lesions, genital cancer and genital warts in women. Drugs 2010; 70 (18): 2449–74PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Department of Obstetrics and Gynaecology, Division of Gynaecologic OncologyMedical University of ViennaViennaAustria

Personalised recommendations