M Reuschenbach1. 1. Abteilung für Angewandte Tumorbiologie, Institut für Pathologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland, miriam.reuschenbach@med.uni-heidelberg.de.
Abstract
BACKGROUND: Up to 70% of oropharyngeal cancers are attributable to human papillomavirus (HPV) infection; however, a therapy specific for patients with HPV-associated cancers is currently not available. Overexpression of the viral oncogenes E6 and E7 results in cellular alterations that represent interesting targets for novel therapies. One consequence of E6/E7 overexpression is strong expression of the cellular protein p16(INK4a). The elimination of p16(INK4a)-expressing tumor cells by the immune system could be achieved through a therapeutic p16(INK4a) vaccine. OBJECTIVE: The current article provides an overview of HPV-associated head and neck cancers and the associated p16(INK4a) expression. Based on this overview, the concept and status of the clinical investigation of therapeutic p16(INK4a) vaccination is described. MATERIAL AND METHODS: In addition to discussing published literature, a clinical study is described. In this phase I/IIa study, patients with advanced HPV-associated p16(INK4a)-expressing tumors were vaccinated with a p16(INK4a) peptide. RESULTS: HPV-associated head and neck cancers continuously display strong overexpression of the cellular protein p16(INK4a). Vaccination with p16(INK4a) could represent a novel therapy for patients with HPV-associated carcinomas. CONCLUSION: Further studies will evaluate the clinical efficacy of therapeutic p16(INK4a) vaccination. Combinations with other immunotherapeutic approaches are interesting considering the modulating role of the immune system, particularly in HPV-associated tumors.
BACKGROUND: Up to 70% of oropharyngeal cancers are attributable to human papillomavirus (HPV) infection; however, a therapy specific for patients with HPV-associated cancers is currently not available. Overexpression of the viral oncogenes E6 and E7 results in cellular alterations that represent interesting targets for novel therapies. One consequence of E6/E7 overexpression is strong expression of the cellular protein p16(INK4a). The elimination of p16(INK4a)-expressing tumor cells by the immune system could be achieved through a therapeutic p16(INK4a) vaccine. OBJECTIVE: The current article provides an overview of HPV-associated head and neck cancers and the associated p16(INK4a) expression. Based on this overview, the concept and status of the clinical investigation of therapeutic p16(INK4a) vaccination is described. MATERIAL AND METHODS: In addition to discussing published literature, a clinical study is described. In this phase I/IIa study, patients with advanced HPV-associated p16(INK4a)-expressing tumors were vaccinated with a p16(INK4a) peptide. RESULTS:HPV-associated head and neck cancers continuously display strong overexpression of the cellular protein p16(INK4a). Vaccination with p16(INK4a) could represent a novel therapy for patients with HPV-associated carcinomas. CONCLUSION: Further studies will evaluate the clinical efficacy of therapeutic p16(INK4a) vaccination. Combinations with other immunotherapeutic approaches are interesting considering the modulating role of the immune system, particularly in HPV-associated tumors.
Authors: Anil K Chaturvedi; Eric A Engels; Ruth M Pfeiffer; Brenda Y Hernandez; Weihong Xiao; Esther Kim; Bo Jiang; Marc T Goodman; Maria Sibug-Saber; Wendy Cozen; Lihua Liu; Charles F Lynch; Nicolas Wentzensen; Richard C Jordan; Sean Altekruse; William F Anderson; Philip S Rosenberg; Maura L Gillison Journal: J Clin Oncol Date: 2011-10-03 Impact factor: 44.544
Authors: Miriam Reuschenbach; Mirjam Seiz; Christina von Knebel Doeberitz; Svetlana Vinokurova; Alexander Duwe; Ruediger Ridder; Heike Sartor; Friedrich Kommoss; Dietmar Schmidt; Magnus von Knebel Doeberitz Journal: Int J Cancer Date: 2011-06-10 Impact factor: 7.396
Authors: M Reuschenbach; S Wagner; N Würdemann; S J Sharma; E-S Prigge; M Sauer; A Wittig; C Wittekindt; M von Knebel Doeberitz; J P Klussmann Journal: HNO Date: 2016-07 Impact factor: 1.284