title: Predicting residual neck disease in patients with oropharyngeal squamous cell carcinoma treated with radiation therapy: utility of p16 status.
abstract: OBJECTIVE
  To identify factors that predict complete response of cervical nodal disease to radiation therapy (RT) in patients with oropharyngeal squamous cell carcinoma (OP-SCCA).
  
  
  METHODS
  Histologic analysis of prospectively collected specimens and retrospective medical chart review.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  Sixty-nine patients with OP-SCCA treated from January 1, 2002, through June 1, 2008.
  
  
  METHODS
  Definitive RT, with or without chemotherapy and with or without neck dissection (ND).
  
  
  METHODS
  Presence of a viable tumor in post-RT ND specimen.
  
  
  RESULTS
  Tissue specimens from 69 patients with OP-SCCA treated primarily with RT, with or without chemotherapy, were evaluated. Of these, 47 (68.1%) were strongly and diffusely positive for p16 expression by immunohistochemical analysis, signifying human papillomavirus positivity. Patients with p16-positive and p16-negative tumors (hereinafter, p16+ and p16-, respectively) had similarly sized primary tumors on presentation, but p16+ primary tumors were associated with more advanced neck disease (nodal stages N2c-N3; 31.9% vs 4.5% for p16- tumors) and more contralateral nodes (27.7% vs 4.5% for p16- tumors). Forty-seven patients (59.0%) underwent planned posttreatment ND (a total of 55 NDs). The NDs performed for p16- tumors were significantly more likely to have viable tumor in the specimen (50.0% vs 18.0% for p16+ tumors; P = .02). In addition, p16+ necks with residual viable cancer were characterized by incomplete response on post-RT imaging, tobacco and alcohol use, and extracapsular spread on pretreatment imaging.
  
  
  CONCLUSIONS
  In conjunction with other clinical parameters, p16 status can help predict the need for post-RT ND in patients with OP-SCCA. Although close observation may be warranted in selected patients with p16+ tumors, patients with p16- tumors are at much higher risk for residual neck disease, even when initial nodal disease is less advanced.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Shonka
authors.forename: Asal N
authors.initials: AN
authors.lastname: Shoushtari
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Thomas
authors.forename: Christopher
authors.initials: C
authors.lastname: Moskaluk
authors.forename: Paul W
authors.initials: PW
authors.lastname: Read
authors.forename: James F
authors.initials: JF
authors.lastname: Reibel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Levine
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Jameson
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins