Current Therapeutic Vaccination and Immunotherapy Strategies for HPV-related Diseases

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2016 Feb 3

PMID 26835746

Citations 42

Authors

Joseph G Skeate

Andrew W Woodham

Mark H Einstein

Diane M Da Silva

W Martin Kast

Affiliations

Soon will be listed here.

Abstract

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Citing Articles

Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.

Tessandier N, Elie B, Boue V, Selinger C, Rahmoun M, Bernat C PLoS Biol. 2025; 23(1):e3002949.

PMID: 39836629 PMC: 11750104. DOI: 10.1371/journal.pbio.3002949.

Association between contextual factors and vaccine coverage against human papilomavirus in adolescents in the state of Minas Gerais, Brazil: global spatial regressions.

Luvisaro B, da Silva T, Gusmao J, Ferraz M, Nascimento L, Gomes L BMC Infect Dis. 2025; 25(1):34.

PMID: 39773132 PMC: 11705653. DOI: 10.1186/s12879-024-10263-w.

Analysis of vaginal flora diversity and study on the role of Porphyromonas asaccharolytica in promoting IL-1β in regulating cervical cancer.

Bai B, Tuerxun G, Tuerdi A, Maimaiti R, Sun Y, Abudukerimu A Sci Rep. 2024; 14(1):21731.

PMID: 39289490 PMC: 11408518. DOI: 10.1038/s41598-024-73146-9.

Head and neck cancer: pathogenesis and targeted therapy.

Liu Y, Zhang N, Wen Y, Wen J MedComm (2020). 2024; 5(9):e702.

PMID: 39170944 PMC: 11338281. DOI: 10.1002/mco2.702.

Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3.

Kawana K, Kobayashi O, Ikeda Y, Yahata H, Iwata T, Satoh T JNCI Cancer Spectr. 2023; 7(6).

PMID: 38001029 DOI: 10.1093/jncics/pkad101.

References

Muderspach L, Wilczynski S, Roman L, Bade L, Felix J, Small L . A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin Cancer Res. 2000; 6(9):3406-16. View

Lukesova E, Boucek J, Rotnaglova E, Salakova M, Koslabova E, Grega M . High level of Tregs is a positive prognostic marker in patients with HPV-positive oral and oropharyngeal squamous cell carcinomas. Biomed Res Int. 2014; 2014:303929. PMC: 4017730. DOI: 10.1155/2014/303929. View

Peng S, Ji H, Trimble C, He L, Tsai Y, Yeatermeyer J . Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6. J Virol. 2004; 78(16):8468-76. PMC: 479075. DOI: 10.1128/JVI.78.16.8468-8476.2004. View

Trimble C, Morrow M, Kraynyak K, Shen X, Dallas M, Yan J . Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b.... Lancet. 2015; 386(10008):2078-2088. PMC: 4888059. DOI: 10.1016/S0140-6736(15)00239-1. View

Da Silva D, Woodham A, Skeate J, Rijkee L, Taylor J, Brand H . Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C. Clin Immunol. 2015; 161(2):197-208. PMC: 4658296. DOI: 10.1016/j.clim.2015.09.003. View

Joura E, Giuliano A, Iversen O, Bouchard C, Mao C, Mehlsen J . A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015; 372(8):711-23. DOI: 10.1056/NEJMoa1405044. View

Trimble C, Peng S, Thoburn C, Kos F, Wu T . Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother. 2009; 59(5):799-803. PMC: 2913444. DOI: 10.1007/s00262-009-0806-4. View

Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L . Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 2007; 13(7):828-35. PMC: 2135607. DOI: 10.1038/nm1609. View

Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H . Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996; 8(5):765-72. DOI: 10.1093/intimm/8.5.765. View

10.

Ault K . 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(9576):1861-1868. DOI: 10.1016/S0140-6736(07)60852-6. View

11.

Carleton H . Pathogenic bacteria as vaccine vectors: teaching old bugs new tricks. Yale J Biol Med. 2010; 83(4):217-22. PMC: 3002147. View

12.

Solares A, Baladron I, Ramos T, Valenzuela C, Borbon Z, Fanjull S . Safety and Immunogenicity of a Human Papillomavirus Peptide Vaccine (CIGB-228) in Women with High-Grade Cervical Intraepithelial Neoplasia: First-in-Human, Proof-of-Concept Trial. ISRN Obstet Gynecol. 2011; 2011:292951. PMC: 3118643. DOI: 10.5402/2011/292951. View

13.

Schmiedeskamp M, Kockler D . Human papillomavirus vaccines. Ann Pharmacother. 2006; 40(7-8):1344-52. DOI: 10.1345/aph.1G723. View

14.

Yang B, Yang A, Peng S, Pang X, Roden R, Wu T . Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination. Cell Biosci. 2015; 5:35. PMC: 4480891. DOI: 10.1186/s13578-015-0025-y. View

15.

Ukpo O, Thorstad W, Lewis Jr J . B7-H1 expression model for immune evasion in human papillomavirus-related oropharyngeal squamous cell carcinoma. Head Neck Pathol. 2012; 7(2):113-21. PMC: 3642256. DOI: 10.1007/s12105-012-0406-z. View

16.

Derre L, Rivals J, Jandus C, Pastor S, Rimoldi D, Romero P . BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. J Clin Invest. 2009; 120(1):157-67. PMC: 2799219. DOI: 10.1172/JCI40070. View

17.

Gomez-Gutierrez J, Elpek K, Montes de Oca-Luna R, Shirwan H, Zhou H, McMasters K . Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice. Cancer Immunol Immunother. 2006; 56(7):997-1007. PMC: 11030956. DOI: 10.1007/s00262-006-0247-2. View

18.

Tan S, de Vries E, van der Zee A, de Jong S . Anticancer drugs aimed at E6 and E7 activity in HPV-positive cervical cancer. Curr Cancer Drug Targets. 2011; 12(2):170-84. DOI: 10.2174/156800912799095135. View

19.

Smith J . Ethnic disparities in cervical cancer illness burden and subsequent care: a prospective view in managed care. Am J Manag Care. 2008; 14(6 Suppl 1):S193-9. View

20.

Steele J, Mann C, Rookes S, Rollason T, Murphy D, Freeth M . T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia. Br J Cancer. 2005; 93(2):248-59. PMC: 2361543. DOI: 10.1038/sj.bjc.6602679. View