Prognostic Value of the P16/P53 Immunohistochemical Association in Oropharyngeal Squamous Cell Carcinomas

IMPORTANCE: Accurate HPV status diagnosis is essential for managing oropharyngeal squamous cell carcinoma. OBJECTIVE: We aimed to refine HPV status determination using a cost-effective and reliable approach by integrating the p53 immunohistochemical marker with the conventional p16 marker. We assessed the association between HPV status and the p16/p53 tumor immunohistochemical status and analyzed patient survival based on p16/p53 expression.Design, Setting, Participants, and Exposures:This retrospective, single-center study included 285 patients with oropharyngeal squamous cell carcinoma (2017-2022) with known p16/p53 immunohistochemical profiles. In a subset of 92 patients, HPV status was formally determined using polymerase chain reaction or in situ hybridization. OUTCOME MEASURES AND Patients with a p16+/p53WT profile had superior 5-year overall survival (82.2%; 108/131) and recurrence-free survival (79.4%; 104/131). Patients with discordant profiles (p16+/p53MT, p16-/p53WT) had survival outcomes similar to HPV-independent oropharyngeal squamous cell carcinomas. CONCLUSION: The p16/p53 immunohistochemical profile appears to be a reliable surrogate marker for HPV status and a strong predictor of survival. It could help identify discordant cases, helping prevent inappropriate therapeutic de-escalation. RELEVANCE: With the advancement of artificial intelligence, integrating additional markers into an algorithmic analysis could further refine patient classification and enable more personalized therapeutic approaches.