Prognostic Value of the P16/P53 Immunohistochemical Association in Oropharyngeal Squamous Cell Carcinomas
Antoine Lagadec1, Nazim Benzerdjeb2,3, Ariane Lapierre3,4
1Service d'Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Hôpital La Croix Rousse, Hospices Civils de Lyon, France.
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 Results:
The p16/p53 test was an excellent predictor of HPV status (specificity: 100%, sensitivity: 98.48%), significantly outperforming p16 alone (P < .01). 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.

