title: [Targeting p16(INK4a) by therapeutic vaccination : Concept and status of clinical investigations in HPV-associated head and neck cancers].
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Abteilung für Angewandte Tumorbiologie, Institut für Pathologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland, miriam.reuschenbach@med.uni-heidelberg.de.
authors.forename: M
authors.initials: M
authors.lastname: Reuschenbach
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047428:Protein Kinase Inhibitors