title: High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer.
abstract: BACKGROUND
  Due to unique biology and prognosis, precise identification of predictive parameters is critical for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Prior studies showing absence of prognostication from extracapsular spread (ECS) and/or high N-classification in surgically-treated p16+ OPSCC necessitate new, evidence-based prognosticators.
  
  
  METHODS
  A prospectively assembled cohort of 220, transoral surgery+neck dissection±adjuvant therapy-treated, p16+ OPSCC patients was analyzed. Disease recurrence and disease-specific survival (DSS) were primary endpoints.
  
  
  RESULTS
  Median follow-up was 59 (12-189) months. Distribution of metastatic node numbers was: 0 in 9.5% (n=21), 1 in 33.6% (n=74), 2 in 17% (n=38), 3 in 14.5% (n=32), 4 in 8.2% (n=18), and ⩾5 in 17% (n=37). ECS was recorded in 80% (n=159), and N2c-N3 in 17% (n=38). Adjuvant radiotherapy and chemoradiotherapy was administered in 44% and 34%. Recurrence developed in 22 patients (10%); 4 local, 5 regional, 2 regional and distant, and 11 distant. The 3- and 5-year DSS estimates were 94.6% and 93%. Multivariable logistic regression identified ⩾5 nodes and T3-T4 classification as predictors for recurrence. In multivariable Cox analyses, ⩾5 nodes, T3-T4 classification and margins were prognostic for DSS. ECS, N2c-N3 classification and smoking were not prognostic.
  
  
  CONCLUSIONS
  Metastatic node number, not ECS or high N-classification is an independent nodal predictor of outcomes in surgically-treated p16+ OPSCC patients. Despite high DSS (~80%), closer surveillance for recurrence is recommended for patients with ⩾5 metastatic nodes.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Parul
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States; Clinical Outcomes Research, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Hiram
authors.initials: H
authors.lastname: Gay
authors.affiliation: Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Wade L
authors.initials: WL
authors.lastname: Thorstad
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States; Pathology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States; Pathology, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Chernock
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Nussenbaum
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: haugheyb@ent.wustl.edu.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Haughey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D013514:Surgical Procedures, Operative / Q000379:methods*; D016019:Survival Analysis
keywords: Adjuvant Radiotherapy; Adjuvant chemotherapy; Extracapsular Spread; Head and neck cancer; Human papillomavirus; Oropharynx cancer; p16 gene; p16-positive