Clin Exp Vaccine Res.  2014 Jul;3(2):168-175. 10.7774/cevr.2014.3.2.168.

Current status of human papillomavirus vaccines

• Kim KS
• Park SA
• Ko KN
• Yi S
• Cho YJ

• KMID: 1730621
• DOI: http://doi.org/10.7774/cevr.2014.3.2.168

Abstract

Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development.

Keyword

Papillomavirus vaccines; Virus-like particle vaccines; Uterine cervical neoplasms; Clinical trial

MeSH Terms

Cervix Uteri
Condylomata Acuminata
Female
Humans
Papillomavirus Vaccines*
Risk Factors
Uterine Cervical Neoplasms
Vaccines
Vaccines, Virus-Like Particle
Papillomavirus Vaccines
Vaccines
Vaccines, Virus-Like Particle

Reference

1. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. Lyon: IARC Press;2004.

2. Zur Hausen H. Human papillomaviruses and their possible role in squamous cell carcinomas. Berlin Heidelberg: Springer;1977.

3. Franco EL, Harper DM. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine. 2005; 23:2388–2394.

4. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12–19.

5. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004; 324:17–27.

6. Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003; 348:518–527.

7. Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002; 55:244–265.

8. Munoz N, Bosch FX, Castellsague X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004; 111:278–285.

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

10. Baker TS, Newcomb WW, Olson NH, Cowsert LM, Olson C, Brown JC. Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991; 60:1445–1456.

11. Schiller JT, Castellsague X, Villa LL, Hildesheim A. An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine. 2008; 26:Suppl 10. K53–K61.

12. 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; 6:271–278.

13. Paavonen J, Jenkins D, Bosch FX, et al. 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. 2007; 369:2161–2170.

14. Draper E, Bissett SL, Howell-Jones R, et al. A randomized, observer-blinded immunogenicity trial of Cervarix((R)) and Gardasil((R)) human papillomavirus vaccines in 12-15 year old girls. PLoS One. 2013; 8:e61825.

15. Kols A, Sherris J. HPV vaccines: promise and challenges. AIDS Info Netw. 2000; 15:13.

16. Padmanabhan S, Amin T, Sampat B, Cook-Deegan R, Chandrasekharan S. Intellectual property, technology transfer and manufacture of low-cost HPV vaccines in India. Nat Biotechnol. 2010; 28:671–678.

17. Cho HJ, Oh YK, Kim YB. Advances in human papilloma virus vaccines: a patent review. Expert Opin Ther Pat. 2011; 21:295–309.

18. McNeil C. Who invented the VLP cervical cancer vaccines? J Natl Cancer Inst. 2006; 98:433.

19. Shi L, Sings HL, Bryan JT, et al. GARDASIL: prophylactic human papillomavirus vaccine development--from bench top to bed-side. Clin Pharmacol Ther. 2007; 81:259–264.

20. Jansen KU, Rosolowsky M, Schultz LD, et al. Vaccination with yeast-expressed cottontail rabbit papillomavirus (CRPV) virus-like particles protects rabbits from CRPV-induced papilloma formation. Vaccine. 1995; 13:1509–1514.

21. Bhambhani A, Chintala RV. HPV vaccine formulations comprising aluminum adjuvant and methods of producing same [Internet]. Geneva: World Intellectual Property Organization;c2012. cited 2014 Feb 17. Available from: http://patentscope.wipo.int/search/en/WO2012177970.

22. Harper DM, Vierthaler SL, Santee JA. Review of Gardasil. J Vaccines Vaccin. 2010; 1:pii 1000107.

23. US Food and Drug Administaration. Vaccines and Related Biological Products Advisory Committee (VRBPAC). VRBPAC background document: Gardasil™ HPV quadrivalent vaccine [Internet]. Silverspring: FDA;c2006. cited 2014 Feb 17. Available from: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4222B3.pdf.

24. Merck & Co. Inc.Gardasil®: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine [Internet]. Whitehouse Station: Merck & Co. Inc.;c2013. cited 2014 Feb 17. Available from: http://www.merck.ca/assets/en/pdf/products/GARDASIL-PM_E.pdf.

25. Haupt RM, Sings HL. The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine Gardasil. J Adolesc Health. 2011; 49:467–475.

26. Merck & Co. Inc. Form 10-K annual report [Internet]. Whitehouse Station: Merck & Co. Inc;c2014. cited 2014 Feb 17. Available from: http://www.merck.com/investors/financials/annual-reports/home.html.

27. Descamps D, Giannini S, Lecrenier N, Stephenne J, Wettendorff MA. Vaccine against HPV [Internet]. Geneva: World Intellectual Property Organization;c2010. cited 2014 Feb 17. Available from: http://patentscope.wipo.int/search/en/WO2010012780.

28. Monie A, Hung CF, Roden R, Wu TC. Cervarix: a vaccine for the prevention of HPV 16, 18-associated cervical cancer. Biologics. 2008; 2:97–105.

29. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004; 364:1757–1765.

30. McKeage K, Romanowski B. AS04-adjuvanted human papillomavirus (HPV) types 16 and 18 vaccine (Cervarix(R)): a review of its use in the prevention of premalignant cervical lesions and cervical cancer causally related to certain oncogenic HPV types. Drugs. 2011; 71:465–488.

31. Garcon N, Chomez P, Van Mechelen M. GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines. 2007; 6:723–739.

32. Ismaili J, Rennesson J, Aksoy E, et al. Monophosphoryl lipid A activates both human dendritic cells and T cells. J Immunol. 2002; 168:926–932.

33. Keam SJ, Harper DM. Human papillomavirus types 16 and 18 vaccine (recombinant, AS04 adjuvanted, adsorbed) [Cervarix]. Drugs. 2008; 68:359–372.

34. US Food and Drug Administaration. Cervarix: human papillomavirus bivalent (types 16 and 18) vaccine, recombinant. Vaccines and Related Biological Products Advisory Committee (VRBPAC) briefing document [Internet]. Silverspring: FDA;c2009. cited 2014 Feb 17. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181371.pdf.

35. US Food and Drug Administaration. Clinical review of biologics license application for human papillomavirus 16, 18 L1 virus like particle vaccine, AS04 adjuvant-adsorbed (Cervarix) [Internet]. Silverspring: FDA;c2009. cited 2014 Feb 17. Available from: http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm237976.pdf.

36. Roteli-Martins CM, Naud P, De Borba P, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012; 8:390–397.

37. Harper DM, Vierthaler SL. Next generation cancer protection: the bivalent HPV vaccine for females. ISRN Obstet Gynecol. 2011; 2011:457204.

38. GlaxoSmithKline plc. Form 20-F: GSK annual report 2012 [Internet]. Brentford: GlaxoSmithKline plc.;c2013. cited 2014 Feb 17. Available from: http://www.gsk.com/content/dam/gsk/globals/documents/pdf/GSK-form-20-F-2012.pdf.

39. Einstein MH, Baron M, Levin MJ, et al. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years. Hum Vaccin. 2011; 7:1343–1358.

40. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004; 5:987–995.

41. Zhang SK, Pan XF, Wang SM, et al. Perceptions and acceptability of HPV vaccination among parents of young adolescents: a multicenter national survey in China. Vaccine. 2013; 31:3244–3249.

42. Pagliusi S, Makhoana M, Datla M, et al. Developing Countries Vaccine Manufacturers Network (DCVMN): engaging to step up for vaccine discovery and access. Meeting report 2012. Vaccine. 2013; 31:3111–3115.

43. Takeda. Annual report 2011 [Internet]. Osaka: Takeda;c2011. cited 2014 Feb 17. Available from: http://www.takeda.com/csr/reports/pdf/index/ar2011_en.pdf.

44. Takeda. Annual report 2013 [Internet]. Osaka: Takeda;c2013. cited 2014 Feb 17. Available from: http://www.takeda.com/investor-information/annual/files/ar2013_en.pdf.

45. Han JE, Wui SR, Park SA, et al. Comparison of the immune responses to the CIA06-adjuvanted human papillomavirus L1 VLP vaccine with those against the licensed HPV vaccine Cervarix in mice. Vaccine. 2012; 30:4127–4134.

46. Mount A, Koernig S, Silva A, Drane D, Maraskovsky E, Morelli AB. Combination of adjuvants: the future of vaccine design. Expert Rev Vaccines. 2013; 12:733–746.

47. Han JE, Wui SR, Kim KS, Cho YJ, Cho WJ, Lee NG. Characterization of the structure and immunostimulatory activity of a vaccine adjuvant, de-O-acylated lipooligosaccharide. PLoS One. 2014; 9:e85838.

48. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009; 302:750–757.

49. US Food and Drug Administration. Gardasil vaccine safety [Internet]. Silverspring: FDA;c2009. cited 2014 Feb 17. Available from: http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm179549.htm.

50. Labadie J. Postlicensure safety evaluation of human papilloma virus vaccines. Int J Risk Saf Med. 2011; 23:103–112.

51. Rubin M. HPV update: what nurse practitioners need to know practical strategies for helping patients and parents understand the importance of HPV vaccination. Washington, DC: National Association of Nurse Practitionors in Woman Health;2011.

52. Murray M. Progress in preventing cervical cancer: updated evidence on vaccination and screening [Internet]. Seattle: Program for Appropriate Technology in Health (PATH);c2010. cited 2014 Feb 17. Available from: http://www.path.org/publications/files/RH_outlook_27_2.pdf.

53. Peres J. For cancers caused by HPV, two vaccines were just the beginning. J Natl Cancer Inst. 2011; 103:360–362.

54. Bazan SB, de Alencar Muniz Chaves A, Aires KA, Cianciarullo AM, Garcea RL, Ho PL. Expression and characterization of HPV-16 L1 capsid protein in Pichia pastoris. Arch Virol. 2009; 154:1609–1617.

55. Rybicki EP, Williamson AL, Meyers A, Hitzeroth II. Vaccine farming in Cape Town. Hum Vaccin. 2011; 7:339–348.

56. Markowitz LE, Tsu V, Deeks SL, et al. Human papillomavirus vaccine introduction: the first five years. Vaccine. 2012; 30:Suppl 5. F139–F148.

57. Centers for Disease Control and Prevention (CDC). Recommendations on the use of quadrivalent human papillomavirus vaccine in males: Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011; 60:1705–1708.