Recent Concepts of Human Papillomavirus Vaccine

Woong Shick Ahn

doi:10.5124/jkma.2007.50.9.778

J Korean Med Assoc > Volume 50(9); 2007 > Article

Ahn: Recent Concepts of Human Papillomavirus Vaccine

Focused Issue of This Month

Cervical Cancer

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2007; 50(9): 778-784.

Published online: September 30, 2007

DOI: http://dx.doi.org/10.5124/jkma.2007.50.9.778

Recent Concepts of Human Papillomavirus Vaccine

Woong Shick Ahn, MD

Department of Obstetrics and Gynecology, The Catholic University of Korea College of Medicine, Korea. ahnws@catholic.ac.kr

Abstract

Two prophylactic human papillomavirus (HPV) vaccines against types 6, 11, 16 and 18 have shown great promise in clinical trials with recent results demonstrating 100% efficacy against persistent HPV infection and development of cervical intraepithelial neoplasia up to five years of follow-up. Published data from the phase-IIb and III trials thus far indicate that the prophylactic HPV L1 virus-like particle vaccine is safe and well-tolerated. It offers HPV-naive women a very high level of protection against HPV persistent infection and cervical intraepithelial lesions associated with the types included in the vaccine. HPV vaccination should be also offered to girls before onset of sexual activity. But there are still questions about several issues of HPV prophylactic vaccination. Prolonged clinical trials should be performed for demonstration of these remaining questions. Finally, prophylactic vaccines against HPV will certainly reduce the incidence of the risk of developing cervical cancer.

Human papilloma virus; Prophylactic vaccine; Therapeutic vaccine

References

1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827-841.

2. Bekkers RL, Massuger LF, Bulten J, Melchers WJ. Epidemiological and cliinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med Virol 2004;14:95-105.

3. Calleja-Macias IE, Kalantari M, Huh J, Ortiz-Lopez R, Rojas-Martinez A, Gonzalez-Guerrero JF, Williamson AL, Hagmar B, Wiley DJ, Villarreal L, Bernard HU, Barrera-Saldaña HA. Genomic diversity of human papillomavirus-16, 18, 31 and 35 isolates in a Mexican population and relationship to European, African, and native American variants. Virology 2004;319:315-323.

4. Dürst M, Gissmann L, Ikenberg H, zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA 1983;80:3812-3815.

5. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342-350.

6. Roden R, Wu TC. Preventative and therapeutic vaccines for cervical cancer. Expert Rev Vaccines 2003;2:495-516. Gives a very detailed and comprehensive overview of vaccines for cervical cancer published in the period at the beginning and before 2003.

7. 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;369:1861-1868.

8. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927.

9. Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Lversen OE, Høye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. 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;25:4931-4939. Epub 2007 Apr 20.

10. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M, Boslego J, Sattler C, Barr E, Koutsky LA. Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928-1943.

11. Paavonen J, Jenkins D, Bosch FX, Naud P, Salmerón J, Wheeler CM, Chow SN, Apter DL, Kitchener HC, Castellsague X, de Carvalho NS, Skinner SR, Harper DM, Hedrick JA, Jaisamrarn U, Limson GA, Dionne M, Quint W, Spiessens B, Peeters P, Struyf F, Wieting SL, Lehtinen MO, Dubin G. HPV PATRICIA study group. 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. Paavonen J, Jenkins. Lancet 2007;369:2161-2170.

12. Carter JJ, Koutsky LA, Hughes JP, Lee SK, Kuypers J, Kiviat N, Galloway DA. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 2000;181:1911-1919. Epub 2000 May 31.

Table 1

Study characteristics and main results reported by three randomised placebo-controlled phase-IIb HPV vaccination trials

ATP; according-to-protocol analysis, CI; 95% confidence interval, GMT; geometric mean titre of antibodies, ITT; intention-to-treat analysis, VLP; virus like particles

^*No cases in vaccinated or placebo group

Table 2

Phase-III vaccination trials, currently being conducted or planned (adapted from Cohen (2005))