title: Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.
abstract: Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
authors.forename: Sung Jong
authors.identifier: http://orcid.org/0000-0002-6077-2649
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0003-0200-9140
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: T C
authors.identifier: http://orcid.org/0000-0003-1623-4584
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Chung2@jhmi.edu.
authors.forename: Chien Fu
authors.identifier: http://orcid.org/0000-0001-9170-7797
authors.initials: CF
authors.lastname: Hung
mesh_terms: D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D030361:Papillomavirus Infections / Q000150:complications* / Q000628:therapy; D053918:Papillomavirus Vaccines / Q000627:therapeutic use; D057170:Translational Research, Biomedical; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D019444:Vaccines, DNA / Q000627:therapeutic use; D022223:Vaccines, Subunit / Q000627:therapeutic use
chemical_list: D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit
keywords: Human Papillomavirus; Immune Checkpoint Inhibitor; Immunotherapy; Therapeutics; Uterine Cervical Neoplasms; Vaccines