title: Epigenetic Mechanisms of Human Papillomavirus-Associated Head and Neck Cancer.
abstract: BACKGROUND
  Growing evidence suggests that as many as half of all oropharyngeal squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections. Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with a better response to therapy and longer patient survival than HPV-negative OPSCCs. Human papillomavirus-positive OPSCC has also been shown to have distinct host gene expression profiles compared with HPV-negative OPSCC. Recently, this distinction has been shown to include the epigenome. It is well supported that cancers are epigenetically deregulated. This review highlights epigenetic differences between HPV-positive and HPV-negative OPSCCs. The epigenetic mechanisms highlighted include methylation changes to host and viral DNA, and host chromatin modification. We also review the current evidence regarding host DNA methylation changes associated with smoking, and deregulation of microRNA expression in HPV-positive OPSCC.
  
  
  OBJECTIVE
  To provide an overview of epigenetic mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and discussion of the challenges involved in studying epigenetic changes in HPV-associated OPSCC in combination with changes associated with smoking.
  
  
  METHODS
  Sources were a literature review of peer-reviewed articles in PubMed on HPV and either OPSCC or head and neck squamous cell carcinoma, and related epigenetic mechanisms.
  
  
  CONCLUSIONS
  Epigenetic changes are reported to be a contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC. The epigenetic mechanisms highlighted in this review can be studied for potential as biomarkers or as drug targets. Furthermore, continued research on the deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV-negative OPSCC) may contribute to our understanding of the clinical and biologic differences between HPV-positive and HPV-negative OPSCC.
authors.forename: Nicole V J
authors.initials: NV
authors.lastname: Anayannis
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.affiliation: From the Departments of Pathology (Ms Anayannis and Dr Belbin), Epidemiology & Population Health (Dr Schlecht), and Medicine (Oncology) (Dr Schlecht), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics* / Q000628:therapy; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006258:Head and Neck Neoplasms / Q000150:complications / Q000235:genetics* / Q000628:therapy; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000235:genetics / Q000628:therapy; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D012907:Smoking