title: Multicentric human papillomavirus-associated head and neck squamous cell carcinoma.
abstract: BACKGROUND
  The purpose of this study was to present the clinicopathological features of a series of patients with human papillomavirus (HPV)-associated head and neck second primary tumors.
  
  
  METHODS
  Patients with HPV-associated head and neck second primary tumors from 3 centers were identified. HPV infection was evaluated using p16 by immunohistochemistry (IHC), high-risk HPV DNA by in situ hybridization (ISH), and HPV genotyping by DNA polymerase chain reaction (PCR) enzyme immunoassay (EIA).
  
  
  RESULTS
  Eleven patients were identified: 5 with synchronous and 6 with metachronous HPV-positive second primary tumors, the latter demonstrating a mean time interval of 5 years. There were 13 second primary tumors: 11 oropharyngeal, 1 nasopharyngeal, and 1 floor of the mouth. Nine of 10 genotyped patients harbored HPV-16, and 1 patient had HPV-33 in 3 synchronous tumors.
  
  
  CONCLUSIONS
  HPV-associated second primary tumors may present as synchronous and/or metachronous lesions and can arise outside the oropharynx after prolonged intervals. Further work is necessary to identify patients at risk and to elucidate the mechanisms of HPV-associated head and neck second primary tumors.
authors.affiliation: Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Caley
authors.forename: Mererid
authors.initials: M
authors.lastname: Evans
authors.forename: Ned
authors.initials: N
authors.lastname: Powell
authors.forename: Vinidh
authors.initials: V
authors.lastname: Paleri
authors.forename: Alun
authors.initials: A
authors.lastname: Tomkinson
authors.forename: Teresa Guerrero
authors.initials: TG
authors.lastname: Urbano
authors.forename: Amrita
authors.initials: A
authors.lastname: Jay
authors.forename: Max
authors.initials: M
authors.lastname: Robinson
authors.forename: Selvam
authors.initials: S
authors.lastname: Thavaraj
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000821:virology*; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: head and neck squamous cell carcinoma; human papillomavirus; multicentric; pharyngeal; second primary tumor