title: p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.
abstract: BACKGROUND
  The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).
  
  
  METHODS
  Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC).
  
  
  RESULTS
  A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer.
  
  
  CONCLUSIONS
  The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Lanea M
authors.initials: LM
authors.lastname: Keller
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Galloway
authors.forename: Thomas
authors.initials: T
authors.lastname: Holdbrook
authors.forename: Karen
authors.initials: K
authors.lastname: Ruth
authors.forename: Donghua
authors.initials: D
authors.lastname: Yang
authors.forename: Cara
authors.initials: C
authors.lastname: Dubyk
authors.forename: Douglas
authors.initials: D
authors.lastname: Flieder
authors.forename: Miriam N
authors.initials: MN
authors.lastname: Lango
authors.forename: Ranee
authors.initials: R
authors.lastname: Mehra
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.forename: John A
authors.initials: JA
authors.lastname: Ridge
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009382:Neoplasms, Unknown Primary / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D030361:Papillomavirus Infections; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins
keywords: concurrent chemotherapy; extracapsular extension (ECE); human papillomavirus (HPV); tissue microarray; unknown primary