Skip to main content

The Need for Therapeutic HPV Vaccines as a Means of Curbing the Menace of Cervical Cancer



One of the leading causes of sexually transmitted diseases and other mucosal and epithelial-associated diseases is human papillomavirus, especially type 16 and 18. African women with normal cytology have been reported to have the highest prevalence of HPV and also higher tendency of developing invasive cervical cancer due to certain sociocultural and economic factors. Despite this, a cost-effective therapy (vaccine) for human papillomavirus is yet to be produced.


HPV vaccination (with prophylactic HPV vaccines) is targeted towards preventing infection, but the public health goal is preventing cervical cancer. However, these vaccines had been found not to be effective in eliminating pre-existing lesions, not effective in clearing established HPV infections, and are very expensive especially in low-income countries; thus, the need for therapeutic HPV vaccines that are geared towards preventing low-grade lesion from progressing, controlling the spread of metastatic cancer, regressing existing lesion and finally preventing recurrence of cancer following treatment is highly sought.


Therapeutic vaccines that broadly target oncogenic HPV types at an early stage, and that are inexpensive, are urgently required.

This is a preview of subscription content, access via your institution.

Fig. 1



Antigen-presenting cells


Cervical intraepithelial neoplasia


Cytotoxic T-lymphocyte


Disability-adjusted life years


Dendritic cells


Double-stranded DNA


Human papillomavirus


High-grade squamous intraepithelial lesion


Long control region


Low-grade squamous intraepithelial lesion


Modified vaccinia Ankara


Major histocompatibility complex


Open reading frames


Small interfering RNA


Synthetic long overlapping peptides


Vaginal intraepithelial neoplasia


Vulva intraepithelial neoplasia


Years lived with disability


Years of life lost


  1. 1.

    Fernandes JV, Meissner RV, de Carvalho MG, Fernandes TAAM, de Azevedo PR, Villa LL. Prevalence of HPV infection by cervical cytologic status in Brazil. Int J Gynaecol Obs. 2009;105(1):2124.

    Google Scholar 

  2. 2.

    Burd EM. Human papillomavirus and cervical cancer. Clin Microbiology Rev. 2003;16(1):1–17.

    CAS  Article  Google Scholar 

  3. 3.

    De Sanjosé S, Diaz M, Castellsagué X, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. The Lancet infect dis. 2007;7(7):453–9.

    Article  Google Scholar 

  4. 4.

    Bayo S, Bosch FX, de Sanjosé S, et al. Risk factors of invasive cervical cancer in Mali. Int J Epidemiol. 2002;31(1):202–9.

    Article  Google Scholar 

  5. 5.

    Thomas JO, Herrero R, Omigbodun AA, et al. Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study. Br J Cancer. 2004;90(3):638–45.

    CAS  Article  Google Scholar 

  6. 6.

    Gage JC, Ajenifuja KO, Wentzensen NA, et al. The age-specific prevalence of human papillomavirus and risk of cytologic abnormalities in rural Nigeria: Implications for screen-and-treat strategies. Int J cancer. 2012;130(9):2111–7.

    CAS  Article  Google Scholar 

  7. 7.

    Fadahunsi OO, Omoniyi-Esan GO, Banjo AAF, et al. Prevalence of high risk oncogenic human papillomavirus types in cervical smears of women attending well woman clinic in Ile Ife Nigeria. Gynecol Obstet. 2013;3(6):185.

    Google Scholar 

  8. 8.

    Ferlay J, Soerjomataram I, Ervik M, et al. Cancer Incidence and Mortality Worldwide. IARCCancerBase. 2013; 11.

  9. 9.

    Bernard HU, Burk RD, Chen Z, van Doorslaer K, Hausen H, de Villiers EM. Classification of papillomavirus (PVs) based on 189 HPV types and proposal of taxonomic amendments. Virology. 2010;401:70–9.

    CAS  Article  Google Scholar 

  10. 10.

    Bosch FX, de Sanjosé S, Castellsagué X. HPV and genital cancer: the essential epidemiology. Vaccine Prev Cerv Cancer. 2008;12:18–22.

    Google Scholar 

  11. 11.

    Stanley MA. Pathology and epidemiology of HPV infection in females. Gynecol Oncol. 2010;117(2):5–10.

    Article  Google Scholar 

  12. 12.

    Conway MJ, Meyers C. Replication and assembly of human papillomaviruses. J Dental Res. 2009;88(4):307–17.

    CAS  Article  Google Scholar 

  13. 13.

    Jo H, Kim JW. Implications of HPV infection in uterine cervical cancer. Cancer Therapy. 2005;3:419–34.

    Google Scholar 

  14. 14.

    Nath AK, Thappa DM. Vaccines for human papillomavirus infection: A critical analysis. Indian J Dermatol Venereol Leprol. 2009;75:245–54.

    Article  Google Scholar 

  15. 15.

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

    CAS  Article  Google Scholar 

  16. 16.

    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;369:2161–70.

    CAS  Article  Google Scholar 

  17. 17.

    Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial. Lancet. 2006;367:1247–55.

    CAS  Article  Google Scholar 

  18. 18.

    Tay EH, Garland S, Tang G, et al. Clinical trial experience with prophylactic HPV 6/11/16/18 VLP vaccine in young women from the Asia-Pacific region. Int J Gynaecol Obstet. 2008;102:275–83.

    CAS  Article  Google Scholar 

  19. 19.

    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;6:271–8.

    Article  Google Scholar 

  20. 20.

    Yusuf L, Bala JA, Aliyu IA, et al. Phytotherapy as an alternative for the treatment of human papillomavirus infections in Nigeria: a review. Afr J Clin Exper Microbiol. 2020;21(3):175–84.

    Google Scholar 

  21. 21.

    World Health Organization. Human papillomavirus vaccines WHO position paper. Wkly Epidemiol Rec. 2009;84(15):118–31.

    Google Scholar 

  22. 22.

    Hildesheim A, Gonzalez P, Kreimer AR, et al. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obst Gynecol. 2016;215(2):212.e1-212.e15.

    Article  Google Scholar 

  23. 23.

    Kash N, Lee MA, Kollipara R, Downing C, Guidry J, Tyring SK. Safety and efficacy data on vaccines and immunization to human papillomavirus. J Clin Med. 2015;4(4):614–33.

    CAS  Article  Google Scholar 

  24. 24.

    Duggan-Keen MF, Brown M, Stacey SN, Stern PL. Papillomavirus vaccines. Front Biosci. 1998;3:1192–208.

    Article  Google Scholar 

  25. 25.

    Lowy DR, Schiller JT. Papillomaviruses and cervical cancer: pathogenesis and vaccine development. J Nat Can Inst Mon. 1998;23:27–30.

    Article  Google Scholar 

  26. 26.

    Brun JL, Dalstein V, Leveque J, et al. Regression of high-grade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy. Am J Obst and Gynecol. 2011;204(2):69.

    Article  Google Scholar 

  27. 27.

    Doorbar J. Model systems of human papillomavirus-associated disease. J Path. 2016;238(2):166–79.

    Article  Google Scholar 

  28. 28.

    Borysiewicz LK, Fiander A, Nimako M, et al. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet. 1996;347(9014):1523–7.

    CAS  Article  Google Scholar 

  29. 29.

    Yang A, Farmer E, Wu TC, Hung C. Perspectives for therapeutic HPV vaccine development. J Biomed Sci. 2016;23:75.

    Article  Google Scholar 

  30. 30.

    Maciag PC, Radulovic S, Rothman J. The first clinical use of a live-attenuated listeria monocytogenes vaccine: a phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix. Vaccine. 2009;27(30):3975–83.

    CAS  Article  Google Scholar 

  31. 31.

    Lin K, Doolan K, Hung CF, Wu TC. Perspectives for preventive and therapeutic HPV vaccines. J Formosan Med Ass. 2010;109(1):4–24.

    CAS  Article  Google Scholar 

  32. 32.

    Coleman HN, Greenfield WW, Stratton SL, et al. Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination. Cancer Immunol Immunother. 2016;65(5):563–73.

    CAS  Article  Google Scholar 

  33. 33.

    van Poelgeest MI, Welters MJ, van Esch EM, et al. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J Transl Med. 2013;11(1):88.

    Article  Google Scholar 

  34. 34.

    Chabedaa A, Romana J, Yaneza R, et al. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Re. 2018;5:46–58.

    Article  Google Scholar 

  35. 35.

    Su JH, Wu A, Scotney E, et al. Immunotherapy for cervical cancer: research status and clinical potential. BioDrugs. 2010;24(2):109–29.

    CAS  Article  Google Scholar 

  36. 36.

    Lee SJ, Yang A, Wu TC, Hung CF. Immunotherapy for human papillomavirus associated disease and cervical cancer: review of clinical and translational research. J Gynecol Oncol. 2016;27(5):e51.

    Article  Google Scholar 

  37. 37.

    Dupuis M, Denis-Mize K, Woo C, et al. Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J Immunol. 2000;165(5):2850–8.

    CAS  Article  Google Scholar 

  38. 38.

    Kim TJ, Jin HT, Hur SY, et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun. 2014;30(5):5317.

    Article  Google Scholar 

  39. 39.

    Kim KW, Hung CF, Juang J, et al. Enhancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death. Gene Ther. 2004;11(3):336–42.

    CAS  Article  Google Scholar 

  40. 40.

    Kim JH, Kang TH, Noh KH, et al. Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell mediated cell death. Immunol Letters. 2009;122(1):58–67.

    CAS  Article  Google Scholar 

  41. 41.

    Santin AD, Bellone S, Palmieri M, et al. Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: a phase I escalating-dose trial. J Virology. 2008;82(4):1968–79.

    CAS  Article  Google Scholar 

Download references


This review received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information




KI, DU, BJ, YL and AI conceptualize the work. KI, AS, BH, KA, BZ and AI carried out literature search. KI, AI, AS, YL, DU and BJ drafted the work. All authors have approved the manuscript as submitted.

Corresponding author

Correspondence to Imam Malik Kabir.

Ethics declarations

Conflict or interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kabir, I.M., Dutsinma, U.A., Bala, J.A. et al. The Need for Therapeutic HPV Vaccines as a Means of Curbing the Menace of Cervical Cancer. Indian J Gynecol Oncolog 19, 96 (2021).

Download citation


  • Human papillomavirus
  • Prophylactic HPV vaccines
  • Therapeutic HPV vaccines
  • Cervical cancer
  • Oncoproteins