title: Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.
abstract: OBJECTIVE
  Discern inter- and intra-observer variability in the classification of extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing pathologists' own criteria versus those of a well-defined classification system.
  
  
  METHODS
  Five pathologists reviewed 50 digitally scanned nodal metastasis slides in three Rounds. Round One was by their own criteria as ECE present or absent, and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no ECE - thick capsule; no infiltration), 1 (ECE - cells beyond capsule), and 2 (soft tissue metastasis - cells in soft tissue without residual node). Round Three assessed intra-observer variability after an 8 month washout period.
  
  
  RESULTS
  In Round One, all five agreed on only 48% of cases (n=24). Fleiss's Kappa value was 0.508 (95% CI: 0.357-0.644). For Rounds Two and Three, Grades 0 and 0c and Grades 1 and 2 were separately grouped as ECE absent or present. In Round Two, all five agreed on 68% of cases (n=34). Fleiss' Kappa was 0.635 (95% CI: 0.472-0.783), indicating statistically significantly better agreement. In Round Three, all five agreed on 64% of cases (n=32) giving a Fleiss's Kappa of 0.639. Pathologists agreed with their prior reads in approximately 90% of cases (average n=45.4, range n=42-49), an average intra-observer Cohen's Kappa of 0.8 (range: 0.68-0.95). Inter- and intra-observer variability rates for classification of soft tissue metastasis (ECE2) were substantially worse.
  
  
  CONCLUSIONS
  There is substantial inter-, and modest intra-, observer variability among head and neck pathologists for ECE in p16+ OPSCC, which is modestly improved by a defined system.
authors: Vanderbilt University Medical Center, Department of Pathology, Microbiology, and Immunology, Nashville, TN, United States; Vanderbilt University Medical Center, Department of Otolaryngology, Nashville, TN, United States; Washington University, Department of Pathology and Immunology, St. Louis, MO, United States. Electronic address: james.lewis@vanderbilt.edu.
authors: James S
authors: JS
authors: Lewis
authors: Washington University, Department of Pathology and Immunology, St. Louis, MO, United States.
authors: Yaman
authors: Y
authors: Tarabishy
authors: Washington University, Division of Biostatistics, St. Louis, MO, United States.
authors: Jingqin
authors: J
authors: Luo
authors: Inova Fairfax Hospital, Department of Pathology, Falls Church, VA, United States.
authors: Haresh
authors: H
authors: Mani
authors: Johns Hopkins University, Department of Pathology, Baltimore, MD, United States.
authors: Justin A
authors: JA
authors: Bishop
authors: H. Lee Moffitt Cancer Center, Department of Pathology and Cell Biology, Tampa, FL, United States.
authors: Marino E
authors: ME
authors: Leon
authors: Yale University, Department of Pathology, New Haven, CT, United States.
authors: Manju L
authors: ML
authors: Prasad
authors: UCLA, Department of Pathology and Laboratory Medicine, Los Angeles, CA, United States.
authors: Haodong
authors: H
authors: Xu
authors: Royal Surrey County Hospital, Department of Histopathology, Guildford, Surrey, United Kingdom.
authors: Silvana
authors: S
authors: Di Palma
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D052162:Human papillomavirus 16; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D015588:Observer Variation; D009959:Oropharyngeal Neoplasms / Q000473:pathology*; D030361:Papillomavirus Infections / Q000473:pathology*; D014481:United States
keywords: Extracapsular extension; Inter-observer variability; Lymph node metastasis; Oropharyngeal squamous cell carcinoma; Soft tissue metastasis; p16