title: Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.
abstract: Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: P
authors.initials: P
authors.lastname: Vici
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: b HPV-UNIT Laboratory of Virology , 'Regina Elena' National Cancer Institute , Rome , Italy.|c Department of Gynecologic Oncology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.affiliation: d Oncology Unit , Nuovo Regina Margherita Hospital , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zampa
authors.affiliation: e Department of Medical Oncology , University Campus Bio-Medico , Rome , Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: L
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: f Medical Oncology Unit, ASL Frosinone , Frosinone , Italy.
authors.forename: T
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: g Department of Medical, Oral and Biotechnological Sciences, Experimental and Clinical Sciences , University 'G. d'Annunzio' , Chieti , Italy.
authors.forename: C
authors.initials: C
authors.lastname: Natoli
authors.affiliation: h Oncology Unit, Sant'Andrea Hospital , 'Sapienza' University of Rome , Rome , Italy.
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.|i Scientific Direction , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Barba
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.|i Scientific Direction , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: a Division of Medical Oncology 2 , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sergi
authors.affiliation: j Department of Gynecologic and Obstetric Sciences , La Sapienza University of Rome , Rome , Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tomao
authors.affiliation: b HPV-UNIT Laboratory of Virology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vizza
authors.affiliation: k Emergency Department , Santa Maria Goretti Hospital , Latina , Italy.
authors.forename: S
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: b HPV-UNIT Laboratory of Virology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: F
authors.initials: F
authors.lastname: Paolini
authors.affiliation: b HPV-UNIT Laboratory of Virology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Curzio
authors.affiliation: c Department of Gynecologic Oncology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Corrado
authors.affiliation: l Oncology Unit I , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: m Radiotherapy , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sanguineti
authors.affiliation: n Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology , Temple University , Philadelphia , PA , USA.|o Department of Human Pathology and Oncology , University of Siena , Siena , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.affiliation: i Scientific Direction , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Maria
authors.affiliation: b HPV-UNIT Laboratory of Virology , 'Regina Elena' National Cancer Institute , Rome , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Venuti
mesh_terms: D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000639:trends; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications*; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines
keywords: Human papillomavirus; cervical cancer; cervical intraepithelial neoplasia; immunotherapy; therapeutic vaccines