title: Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas--a tissue microarray study utilizing E6/E7 mRNA in situ hybridization.
abstract: OBJECTIVE
  Human papillomavirus is well established in oropharyngeal squamous cell carcinoma as both causative and prognostic, but its significance in non-oropharyngeal tumours is unclear. In particular, the significance of finding viral DNA is not known. We sought to evaluate nonoropharyngeal squamous cell carcinomas for transcriptionally-active human papillomavirus and to compare this with the presence of viral DNA.
  
  
  METHODS
  We evaluated an 87 patient tissue microarray cohort of oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas for high risk human papillomavirus DNA and E6 and E7 mRNA transcripts by in situ hybridization, and for p16 expression by immunohistochemistry.
  
  
  RESULTS
  We found only two of the 73 (2.7%) evaluable cases to harbour transcriptionally-active human papillomavirus. Both of these tumours were from the larynx, one was positive for human papillomavirus DNA by in situ hybridization, and both were extensively positive for p16. All oral cavity and hypopharyngeal tumours were negative for human papillomavirus.
  
  
  CONCLUSIONS
  Transcriptionally-active human papillomavirus appears to be rare in laryngeal, hypopharyngeal, and oral cavity squamous cell carcinomas. As such, it appears unlikely to be a 'driver' or to be clinically significant in most established tumours.
authors.affiliation: Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA. jlewis@path.wustl.edu
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Odey C
authors.initials: OC
authors.lastname: Ukpo
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.forename: John J
authors.initials: JJ
authors.lastname: Flanagan
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.forename: Wade L
authors.initials: WL
authors.lastname: Thorstad
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Chernock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology / Q000821:virology; D017403:In Situ Hybridization; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D046888:Tissue Array Analysis; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger