Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumor status.

AIMS Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5%-20% of p16-positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC-related HPV. There is, therefore, a risk of undertreating a proportion of OPSCC patients falsely considered as HPV-driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumor status in OPSCC. METHODS AND RESULTS 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16-positive or p16-negative/wild-type patterns-p53 (WT-p53) cases (n = 63), DNA in-situ hybridization for high-risk HPV was performed and if negative, the HPV status was controlled by HPV DNA PCR (n=19). A significant association between TP53 mutation and pattern of p53 expression was found (WT-p53, 7/16, P<0.001). The p16-positive/WT-p53 was significantly associated with HPV+ tumor status (p16-positive/WT-p53, 50/110, P<0.001). Interestingly, a subset of p16-positive OPSCC was unrelated to HPV (13.5%, 8/59) and showed mutant-type staining of p53 expression. CONCLUSIONS The p16 protein immunopositivity in conjunction with the mutant-type pattern of p53 staining helped to reclassify a subset of p16-positive OPSCC as OPSCC-unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.