title: p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status.
abstract: BACKGROUND
  In the human papillomavirus (HPV) era, the best way to assess oropharyngeal squamous carcinomas (SCC) for risk stratification is not clear. Many recommend use of both p16 immunohistochemistry and HPV in situ hybridization (ISH). A significant minority of tumors are p16 positive and HPV ISH negative, the significance of which is unclear.
  
  
  METHODS
  Two hundred thirty-nine oropharyngeal SCC were tested by immunohistochemistry for p16 and by ISH for high-risk HPV. For p16 positive, HPV ISH negative cases, PCR was conducted for HPV. The findings were correlated with pathologic and clinical findings.
  
  
  RESULTS
  Of the 239 cases, 187 (78%) were positive for p16. Of these, 139 (74%) were positive for HPV by ISH. Of the remaining 48 cases, 45 had material for PCR. Nineteen were positive for HPV, leaving a group of 26 p16 positive and HPV undetectable SCCs. In the p16 positive cohort, there was no difference in survival between HPV ISH positive and negative cases. Comparing the HPV ISH positive and HPV ISH and PCR negative SCC, there was again no difference in survival. p16 positive, HPV negative SCC still had significantly better survival than p16 negative SCC in univariate and multivariate analysis.
  
  
  CONCLUSIONS
  Outcomes for p16 positive, HPV negative oropharyngeal SCC are not significantly different from p16 positive, HPV positive tumors and are significantly better than for p16 negative tumors. These results suggest that p16 immunohistochemistry alone is the best test to use for risk stratification in oropharyngeal SCC.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA. jlewis@path.wustl.edu
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Wade L
authors.initials: WL
authors.lastname: Thorstad
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Chernock
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Haughey
authors.forename: James H
authors.initials: JH
authors.lastname: Yip
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Samir K
authors.initials: SK
authors.lastname: El-Mofty
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral