title: Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: a critical analysis of patterns and outcomes.
abstract: OBJECTIVE
  With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16-negative disease.
  
  
  METHODS
  Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed.
  
  
  RESULTS
  Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI: 8-32.5%, p=0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95% CI: 7-18%) while all p16-negative patients died within 34 months (p<0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis.
  
  
  CONCLUSIONS
  The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Thorstad
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nussenbaum
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Haughey
authors.affiliation: Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Adkins
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: jlewis@path.wustl.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*
keywords: Distant metastasis; Human papillomavirus; Oligometastasis; Oropharynx carcinoma; p16-Positive