Are Histomorphological Features Predictive of p16 Immunopositivity Different for Oral and Oropharyngeal Squamous Cell Carcinoma?

Evidence from current studies show that squamous cell carcinomas at oral and oropharyngeal sites are distinct and unique, with their own separate etiopathogenesis, treatment, and prognosis. The aim of this work is to correlate p16 immunohistochemical expression with histomorphological features suggestive of HPV infection in oral and oropharyngeal squamous cell carcinoma. A total of 50 consecutive biopsy cases of oral squamous cell carcinoma (OSCC) and 50 consecutive biopsy cases of oropharyngeal squamous cell carcinoma (OPSCC) were evaluated for features suggestive of HPV infection like focal basaloid appearance, nests, and lobules of tumor cells with pushing borders, absence of stromal reaction, central necrosis, focal lymphoepithelial morphology, presence of koilocytes, and non-keratinizing or hybrid morphology. Immunostaining was performed using p16 monoclonal antibody (clone mouse 16P04). Only cases showing a moderate (2+) to high intensity (3+) staining in more than 75% cells were taken as p16 immunopositive. The histological features were correlated with p16 immunopositivity. A total of 18/50 (36%) cases of oral squamous cell carcinoma and 27/50 (54%) cases of oropharyngeal squamous cell carcinoma were p16 immunopositive. On statistical analysis, only nests/lobules with pushing borders were found to have a significant correlation with p16 immunopositivity ( value = 0.0012) for OSCC cases. For OPSCC cases, four histological features namely nests and lobules with pushing borders ( value = 0.0001), focal basaloid appearance ( value = 0.0041), lymphoepithelial morphology ( value = 0.0029), and non-keratinizing/hybrid morphology ( value = 0.0141) had a significant correlation with p16 immunopositivity. Histomorphological features are more helpful in predicting p16 immunopositivity in OPSCC than OSCC.