title: Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines.
abstract: Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, and de novo immune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed.
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA mnakagawa@uams.edu.
authors.forename: Mayumi
authors.identifier: http://orcid.org/0000-0002-0377-4613
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Obstetrics & Gynecology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: William
authors.initials: W
authors.lastname: Greenfield
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Moerman-Herzog
authors.affiliation: Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Hannah N
authors.initials: HN
authors.lastname: Coleman
mesh_terms: D056738:Cross Protection; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000628:therapy* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016896:Treatment Outcome; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000628:therapy* / Q000821:virology
chemical_list: D000939:Epitopes; D053918:Papillomavirus Vaccines