title: Immunologic treatments for precancerous lesions and uterine cervical cancer.
abstract: Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.forename: Luciano
authors.initials: L
authors.lastname: Mariani
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.forename: Enrico
authors.initials: E
authors.lastname: Vizza
authors.forename: Federica
authors.initials: F
authors.lastname: Tomao
authors.forename: Silverio
authors.initials: S
authors.lastname: Tomao
authors.forename: Claudia
authors.initials: C
authors.lastname: Cavallotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Paolini
authors.affiliation: HPV Unit, Regina Elena National Cancer Institute, V Elio Chianesi 53, Rome 00144, Italy. venuti@ifo.it.
authors.forename: Aldo
authors.initials: A
authors.lastname: Venuti
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy*; D011230:Precancerous Conditions / Q000276:immunology / Q000628:therapy* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines