J Korean Med Assoc.  2007 Feb;50(2):151-158. 10.5124/jkma.2007.50.2.151.

Prophylactic Vaccine for Cervical Carcinoma

• Kim YT

• KMID: 2137788
• DOI: http://doi.org/10.5124/jkma.2007.50.2.151

Abstract

Cervical cancer is the second most common malignant neoplasm affecting women worldwide, with a high rate of mortality throughout the world. Since epidemiologic, biologic, and genetic data have identified a consistent association of human papillomavirus (HPV) infection with cervical cancer development, many researchers have worked on the development of HPV vaccine to establish an efficient program to manage cervical carcinoma in developed countries. Therefore, the aims of this study are to overview the current status of vaccine and to systematically analyze the development process of HPV vaccine through a review of the literature. The basic and clinical data on HPV vaccine inside and outside the country were collected by Medline searching. Recent lines of research on the safety and efficacy of candidate prophylactic vaccines against HPV have shown very promising results with nearly 100% efficacy in preventing persistent infections and the development of cervical precancerous lesions. The variable routes of vaccine administration have been tried-nasal and oral vaccination, as well as parental injection. Recently, clinical trials involving a large population and multi-institutions are ongoing, and also clinical trials are expected in Korea. Although the results of previous HPV vaccine studies are invariably encouraging, several drawbacks need to be addressed. Because the genotype of HPV is regionally different, Korean-specific vaccine needs to be developed, and there are many unsolved problems regarding, for example, the booster injection, optimal timing of vaccination, and vaccination in men.

Keyword

Human papillomavirus vaccine; Cervical cancer; Human papillomavirus

MeSH Terms

Developed Countries
Female
Genotype
Humans
Korea
Male
Mortality
Parents
Uterine Cervical Neoplasms
Vaccination
Vaccines
Vaccines

Figure

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  Figure 1 Natural history of human papillomavirus infection

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  Figure 2 Structure of virus-like particle

Reference

1. zur Hausen H. Human papillomaviruses and their possibel role in squamous cell carcinoma. Curr Top Microbiol Immunol. 1977. 78:1–30.

2. Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, Beckmann AM, Derouen TA, Galloway DA, Vernon D, Kiviat NB. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992. 327:1272–1278.

3. Campion MJ, McCance DJ, Cuzick J, Singer A. Progressive potential of mild cervical atypia: prospective cytological, colposcopic, and virological study. Lancet. 1986. 2:237–240.

4. Ada G. Progress towards achieving new vaccine and vaccination goals. Internal medicine journal. 2003. 33:297–304.

5. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. Papillomavirus L1 major capsid protein self-assembles into viruslike particles that are highly immunogenic. Proc Natl Acad Sci USA. 1992. 89:12180–12184.

6. Hagensee ME, Yaegashi N, Galloway DA. Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. J Virol. 1993. 67:315–322.

7. Zhou J, Sun XY, Davies H, Crawford L, Park D, Frazer IH. Definition of linear antigenic regions of the HPV16 L1 capsid protein using synthetic virion-like particles. Virology. 1992. 189:592–599.

8. Sasagawa T, Pushko P, Steers G, Gschmeissner SE, Hajibagheri MA, Finch J, Crawford L, Tommasino M. Synthesis and assembly of virus-like particles of human papillomaviruses type 6 and type 16 in fission yeast Schizosaccharomyces pombe. Virology. 1995. 206:126–135.

9. Benyacoub J, Hopkins S, Potts A, Kelly S, Kraehenbuhl JP, Curtiss R 3rd, De Grandi P, Nardelli-Haefliger D. The nature of the attenuation of Salmonella typhimurium strains expressing human papillomavirus type 16 virus-like particles determines the systemic and mucosal antibody responses in nasally immunized mice. Infect Immun. 1999. 67:3674–3679.

10. Nardelli-Haefliger D, Roden RB, Benyacoub J, Sahli R, Kraehenbuhl JP, Schiller JT, Lachat P, Potts A, De Grandi P. Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice. Infect Immun. 1997. 65:3328–3336.

11. 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.

12. Kirnbauer R, Taub J, Greenstone H, Roden R, Durst M, Gissmann L, Lowy DR, Schiller JT. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993. 67:6929–6936.

13. Kirnbauer R, Chandrachud LM, O'Neil BW, Wagner ER, Grindlay GJ, Armstrong A, McGarvie GM, Schiller JT, Lowy DR, Campo MS. Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization. Virology. 1996. 219:37–44.

14. Donnelly JJ, Martinez D, Jansen KU, Ellis RW, Montgomery DL, Liu MA. Protection against papillomavirus with a polynucleotide vaccine. J Infect Dis. 1996. 173:314–320.

15. Sundaram P, Tigelaar RE, Brandsma JL. Intracutaneous vaccination of rabbits with the cottontail rabbit papillomavirus (CRPV) L1 gene protects against virus challenge. Vaccine. 1997. 15:664–671.

16. Stanley MA, Moore RA, Nicholls PK, Santos EB, Thomsen L, Parry N, Walcott S, Gough G. Intra-epithelial vaccination with COPV L1 DNA by particle-mediated DNA delivery protects against mucosal challenge with infectious COPV in beagle dogs. Vaccine. 2001. 19:2783–2792.

17. Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis. 1995. 171:1387–1398.

18. Russell MW, Moldoveanu Z, White PL, Sibert GJ, Mestecky J, Michalek SM. Salivary, nasal, genital, and systemic antibody responses in monkeys immunized intranasally with a bacterial protein antigen and the Cholera toxin B subunit. Infect Immun. 1996. 64:1272–1283.

19. Rose RC, Lane C, Wilson S, Suzich JA, Rybicki E, Williamson AL. Oral vaccination of mice with human papillomavirus viruslike particles induces systemic virus-neutralizing antibodies. Vaccine. 1999. 17:2129–2135.

20. Balmelli C, Roden R, Potts A, Schiller J, De Grandi P, Nardelli-Haefliger D. Nasal immunization of mice with human papillomavirus type 16 virus-like particles elicits neutralizing antibodies in mucosal secretions. J Virol. 1998. 72:8220–8229.

21. Liu HL, Li WS, Lei T, Zheng J, Zhang Z, Yan XF, Wang ZZ, Wang YL, Si LS. Expression of human papillomavirus type 16 L1 protein in transgenic tobacco plants. Acta biochimica et biophysica sinica. 2005. 37:153–158.

22. Nardelli-Haefliger D, Wirthner D, Schiller JT, Lowy DR, Hildesheim A, Ponci F, De Grandi P. Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles. J Natl Cancer Inst. 2003. 95:1128–1137.

23. Kawana K, Yasugi T, Kanda T, Kino N, Oda K, Okada S, Kawana Y, Nei T, Takada T, Toyoshima S, Tsuchiya A, Kondo K, Yoshikawa H, Tsutsumi O, Taketani Y. Safety and immunogenicity of a peptide containing the crossneutralization epitope of HPV16 L2 administered nasally in healthy volunteers. Vaccine. 2003. 21:4256–4260.

24. Evans TG, Bonnez W, Rose RC, Koenig S, Demeter L, Suzich JA, O'Brien D, Campbell M, White WI, Balsley J, Reichman RC. A Phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers. J Infect Dis. 2001. 183:1485–1493.

25. Harro CD, Pang YY, Roden RB, Hildesheim A, Wang Z, Reynolds MJ, Mast TC, Robinson R, Murphy BR, Karron RA, Dillner J, Schiller JT, Lowy DR. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 viruslike particle vaccine. J Natl Cancer Inst. 2001. 93:284–292.

26. Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU. Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002. 347:1645–1651.

27. Ault KA, Giuliano AR, Edwards RP, Tamms G, Kim LL, Smith JF, Jansen KU, Allende M, Taddeo FJ, Skulsky D, Barr E. A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine. Vaccine. 2004. 22:3004–3007.

28. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G. GlaxoSmithKline HPV Vaccine Study Group. 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.

29. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. 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.