title: Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.
abstract: OBJECTIVE
  In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan.
  
  
  METHODS
  Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus.
  
  
  RESULTS
  In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status.
  
  
  CONCLUSIONS
  p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan saitou-tky@umin.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Omura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Fujimoto
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Mizuo
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Asakage
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012907:Smoking; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins
keywords: HPV; Japanese; oropharyngeal carcinoma; p16; prognosis