Recognition of nonkeratinizing morphology in oropharyngeal squamous cell carcinoma - a prospective cohort and interobserver variability study

Aims: Nonkeratinizing morphology in oropharyngeal squamous cell carcinoma (NKSCC) strongly correlates with human papillomavirus and p16 status, but as a unique diagnostic entity is not widely recognized by pathologists. We sought to prospectively examine the performance of a new histological typing system during 1year of routine clinical practice (Aim 1) and also its reproducibility amongst six head and neck pathologists using a 40 case test set (Aim 2). Methods and Results: The three histological types were: Type 1 (keratinizing), Type 2 (nonkeratinizing with maturation) and Type 3 (nonkeratinizing). For Aim 1, there were 85 cases. p16 immunohistochemistry was positive in five of the 18 (27.8%) cases classified as Type 1, 18 of the 19 (94.7%) as Type 2, and 47 of the 48 (97.9%) as Type 3. For Aim 2, agreement among pathologists on the test cases was best for types 1 and 3 (kappa values 0.62 and 0.56; P<0.0001) and lowest for type 2 (kappa 0.35; P<0.0001). All 21 cases classified as NK SCC (type 3) by any of the reviewers was p16 positive. Conclusions: Pathologists can recognize NK SCC with good agreement, and when a pathologist classifies a tumour as NK SCC, this reliably predicts p16 positivity.