Advances in human papilloma virus vaccines: a review


  • Akhilesh Tomar Department of Microbiology, R.D. Gardi Medical College, Ujjain-456006, M.P., India,
  • Anjali Kushwah Department of Pharmacology, G.R. Medical College, Gwalior-474009, M.P., India


Cervical Cancer, HPV, Vaccines


Cervical cancer is the second most common cancer among women and third leading cause of cancer death. Approximately 500,000 women worldwide develop new cases of cervical cancer annually, with 80% of these new cases occurring in developing countries. Human papilloma virus (HPV) infection is the main factor associated with the development of cervical cancer.  The currently available HPV vaccines, gardasil and cervarix, can prevent infection by certain HPV types, but not all. At present, research efforts are being devoted to developing broader spectrum preventative vaccines, as well as therapeutic vaccines. To confer additional therapeutic activities, chimeric vaccines have been developed.  Multivalent vaccine technologies employ strategies for addressing a broader spectrum of HPV types or for combining HPV with other pathogens. Edible vaccines are also disclosed.  For needleless immunization, jet gun, gene gun and microneedles have been developed.  Biodegradable and mucoadhesive polymer-based vaccine formulations have been developed to deliver vaccines through the mucosa and enhance immunogenicity. Various viral vectors of recombinant HPV DNA vaccine are disclosed. 


Sankarnaranayan R, Ferlay J. Worldwide burden of gynaecological cancer. The size of the problem. Best Pract Res Clin Obstet Gynaecol. 2006;20:207-25.

WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) Human papillomavirus and related cancers in India. Summary Report. 2010. Available at: Accessed 16 December 2013.

Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.

Bulk S, Berkhof J, Bulkmans NW, Zielinski GD, Rozendaal L, van Kemenade FJ et al. Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adeno- carcinoma of the cervix compared to women with normal cytology in The Netherlands. Br J Cancer. 2006;94:171–5.

Clifford G, Franceschi S, Diaz M, Munoz N, Villa LL. Chapter 3: HPV type - distribution in women with and without cervical neoplastic diseases. Vaccine. 2006;24(Suppl 3):S26–34.

Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJF and Meijer CJLM. International Agency for Research on Cancer Multicenter cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. New Engl. J. Med. 2003;348:518–27.

Harper DM. Currently approved prophylactic HPV vaccines. Expert Rev Vaccines. 2009;8(12):1663-79.

Trottier H, Mahmud S, Costa MC, Sobrinho JP, Duarte-Franco E, Rohan TE, Ferenczy A, Villa LL and Franco EL. Human papillomavirus infections with multiple types and risk of cervical neoplasia. Cancer Epidemiol. Biomarkers Prev. 2006;15:1274–80.

Carter JJ, Koutsky LA, Hughes JP, Lee SK, Kuypers J, Kiviat N et al. Comparison of Human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis. 2000;181:1911-9.

Munoz N, Mendez F, Posso H, Molano M, van den Brule AJ, Ronderos M et al. Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results. J Infect Dis. 2004;190:2077- 87.

Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, Bratti MC et al. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis. 2005;191:1808-16.

Kjaer SK, Chackerian B, van den Brule AJ, Svare EI, Paull G, Walbomers JM et al. High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiol Biomarkers Prev. 2001;10:101-6.

Antonsson A, Karanfilovska S, Lindqvist PG, Hansson BG. General acquisition of human papillomavirus infections of skin occurs in early infancy. J Clin Microbiol. 2003;41:2509-14.

Franceschi S, Herrero R, Clifford GM, Snijders PJ, Arslan A, Anh PT et al. Variations in the age- specific curves of human papillomavirus prevalence in women worldwide. Int J Cancer. 2006Dec1;119(11):2677-84.

Clifford GM, Goncalves MA, Franceschi S; for the HPV and HIV Study Group. Human papillomavirus types among women infected with human immunodeficiency virus: a meta-analysis. AIDS. 2006Dec;20(18):2337-44.

Palefsky JM, Gillison ML, Strickler HD. Chapter 16: HPV vaccines in immunocompromised women and men. Vaccine. 2006;24:S140-6.

Franco E, Villa L, Rohan T, Ferenczy A, Petzl-Erler M, Matlashewski G. Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig- McGill Study Group. Rev Panam Salud Publica. 1999;6:223-33.

Vaccarella S, Franceschi S, Herrero R, Munoz N, Snijders PJ, Clifford GM et al. Sexual behavior,condom use, and human papillomavirus: pooled analysis of the IARC human papillomavirus prevalence surveys. Cancer Epidemiol Biomarkers Prev. 2006;15(2):326-33.

Vaccarella S, Herrero R, Dai M, Snijders PJF, Meijer CJLM, Thomas JO, et al. Reproductive factors, oral contraceptive use and HPV infection: pooled analysis of the IARC HPV Prevalence Surveys. Cancer Epidemiol Biomarkers Prev. 2006.Nov;15(11):2148 53.

Jamison JH, Kaplan DW, Hamman R, Eagar R, Beach R, Douglas JM Jr. Spectrum of genital humanpapillomavirus infection in a female adolescent population. Sex Transm Dis. 1995;22:236-43.

Young TK, McNicol P, Beauvais J. Factors associated with human papillomavirus infection detected by polymerase chain reaction among urban Canadian aboriginal and non-aboriginal women. Sex Transm Dis. 1997;24:293-8.

De Sanjose S, Almirall R, Lloveras B, Font R, Diaz M, Munoz N et al. Cervical human papillomavirus infection in the female population in Barcelona, Spain. Sex Transm Dis. 2003;30:788-93.

Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, De Sanjose S, et al. Male Circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med. 2002;346:1105-12.

Hines JF et al. Prospects for human papillomavirus vaccine development: emerging HPV vaccines. Current Opinion in Obstetrics & Gynecology. 1998;10(1):15-19.

Lowy, DR and Schiller, JT. Papillomaviruses: prophylactic vaccine prospects. Biochimica et al. Biophysica Acta. 1998;1423:M1-8.

NIAID Task Force on Immunology. Report of the NIAID Task Force on Immunology U.S. Department of Health Human Services, Bethesda MD. 1998. Available at: Accessed September 1998.

Duggan-Keen MF et al. Papillomavirus vaccines. Frontiers in Bioscience. 1998;3:1192-208.

Van Driel WJ et al. Immunotherapeutic strategies for cervical squamous carcinoma. Current Therapeutic Issues in Gynecologic Cancer. 1999;13(1):259-71.

Tindle, R. Human papillomavirus vaccines for cervical cancer. Current Opinion in Immunology. 1996;8(5):643-50.

Lowy, DR and Schiller, JT. Papillomaviruses and cervical cancer: pathogenesis and vaccine development. Journal of the National Cancer Institute Monographs. 1998;23:27-30.

Coursaget, P and Munoz, N. Vaccination against infectious agents associated with human cancer. Cancer Surveys. 1999;33:355-81.

Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, 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;364:1757–65.

Paavonen J, Jenkins D, Bosch FX, Naud P, Salmeron J, Wheeler CM 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 randomized controlled trial. Lancet. 2007;369:2161–70.

Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccineagainst human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367:1247– 55.

Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR 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;6:271–8.

Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE 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;95:1459–66.

Villa LL, Ault KA, Giuliano AR, Costa RL, Petta CA, Andrade RP et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006;24:5571–83.

Ault KA. The 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 randomized clinical trials. Lancet. 2007;369:1861–8.

The Future II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–27.

Arbyn M, Dillner J. Review of current knowledge on HPV vaccination: an appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening. J Clin Virol. 2007;38:189–97.

Schiller JT, Frazer IH, Lowy DR. Human Papilloma Virus Vaccines. In: Plotskin SA, Orenstein WA, editors. Vaccines. 5th ed. Philadelphia: Saunders; 2008: 243 -257.

Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Onger ER. Quadrivalent Human Papilloma Virus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomn Rep. 2007;56:1-24.

Singhal T. Indian Academy of Pediatrics Committee on Immunisation (IAPCOI) - Consensus Recommendations on Immunization. Indian Pediatr. 2008;45:6348.

Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD 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;118:2135.

Barnabas RV, Laukkanen P, Koskela P, Kontula O, Lehtinen M, Garnett GP Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modeling analyses. PLoS Med. 2006;3:e138.

Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002;347:1645–51.

Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley DJ et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2006;107:18–27.

Brown D. The Future II Study Group. HPV type 6/11/16/18 vaccine: first analysis of cross-protection against persistent infection, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS) caused by oncogenic HPV types in addition to 16/18. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago IL. 2007September;Presentation number:G1720b:17-20.

Kane MA, Sherris J, Coursaget P, Aguado T, Cutts F. Chapter 15: HPV vaccine use in the developing world. Vaccine. 2006;24:S132-9.

Tindle, R. Human papillomavirus vaccines for cervical cancer. Current Opinion in Immunology. 1996;8(5):643-50.

Duggan-Keen MF et al. Papillomavirus vaccines. Frontiers in Bioscience. 1998;3:1192-208.

Donnelly JJ et al. Protection against papillomavirus with a polynucleotide vaccine. Journal of Infectious Disease. 1996;173:314-20.

Robinson HL et al. The Scientific Future of DNA for Immunization. American Society for Microbiology Washington, D.C. 1997. Available at:

P Lal, VG Ramachandran, R Goyal, R Sharma. Edible Vaccines: Current Status and Future. Indian Journal of Medical Microbiology. 2007:25:93-102.

Franco EL, Cuzick J, Hildesheim A, De Sanjose S. Chapter 20: Issues in planning cervical cancer screening in the era of HPV vaccination. Vaccine. 2006;24(Suppl 3):S3/171-7.




How to Cite

Tomar, A., & Kushwah, A. (2017). Advances in human papilloma virus vaccines: a review. International Journal of Basic & Clinical Pharmacology, 3(1), 37–43. Retrieved from



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