A proposal for classification of oropharyngeal squamous cell carcinoma: morphology and status of HPV by immunohistochemistry and molecular biology

The current three‐tier grading system (well, moderate and poorly differentiated) used to morphologically classify head and neck squamous cell carcinoma (HNSCC) is inadequate for categorisation of oropharyngeal squamous cell carcinoma (OPSCC) owing to the lack of prognostic value. The aim of this study was to assess the validity of a classification system for OPSCC based on morphology and human papilloma virus (HPV) infection status. Haematoxylin and eosin slides of 121 patients (100 M, 21 F, age range 40‐89 years) with OPSCC were reviewed and categorised as histological types I, II and III. The presence of HPV was assessed by immunohistochemistry with p16 and RNAscope In situ hybridization (ISH). The follow‐up period was 36 months. Ninety‐six patients were p16+ and clinical stage I. Patient survival with types I, II and III was 93%, 50% and 96%, respectively. Twenty‐five patients were p16−: 10 clinical stage I and 15 stage III. Amongst this group, no type I morphology was identified. At follow‐up, 65% of type II and 75% of type III patients were alive. All p16+ cases were also positive for E6/E7 mRNA high‐risk HPV by ISH, while 23 p16− cases were negative and two were positive. Cox regression identified three predictors of mortality: older age (HR = 1.14, 95% CI = 1.06‐1.23, P = .001); female gender (HR = 0.22.95% CI 0.05‐0.88, P = .033); and type II morphology (HR = 13.1, 95% CI = 1.09‐157.0, P = .043). OPSCC morphological classification in three sub‐types, along with HPV infection status, seems to reflect the outcome of patients with OPSCC.