CD8+T Cells and PD-L1 Expression as Prognostic Indicators in a Low Prevalence of HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Human papillomavirus (HPV) infection detected in oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better survival outcome from previous literature. However, Thailand and several Asian countries have a low prevalence of HPV-associated OPSCC and, therefore, have a low positive rate of immunostaining with p16. Tumor microenvironments (TME), including tumor-infiltrating CD8+ lymphocytes (CD8+ TIL) and programmed death ligand 1 (PD-L1), are proposed as significant prognostic indicators in addition to p16. Objectives: Explore the expression p16, CD8+ TIL, and PD-L1 and its value as prognostic indicators for overall survival (OS) in patients with OPSCC. Materials and Methods: Data from patients with OPSCC diagnosed from 2012 to 2018 were recovered from medical records and national registry. All available glass slides and slides of immunohistochemistry (IHC) of p16, CD8, and PD-L1 were reviewed. The TME was classified into four types according to the expression pattern of PD-L1 and CD8+TIL. Overall survival (OS) was assessed using the Kaplan-Meier method and Cox regression model analysis. Results: In 160 OPSCC patients, p16 was positive in 27 (16.88%). The density of CD8+ TIL was higher in the p16+ and PD-L1+ groups (p = 0.005, 0.039); however, there was no association between p16 and the status of PD-L1. P16 and CD8+ TIL were significant prognostic factors for better OS (p = 0.007, 0.001), but not PD-L1 status (p = 0.317). Among the four types of TME, carcinoma showed mainly type IV TME (PD-L1-/TIL+), while OPSCCs with type I TME (PD-L1+/TIL+) had the best survival outcome. Conclusions: The positivity of p16 and the density of CD8+ TIL were associated with better OS in OPSCC, while the status of PD-L1 was not significantly related to OS. OPSCC with type I TME (PD-L1+/TIL+) showed the best prognosis of all types of TME.

Automated summary

This study explored the expression of p16, CD8+ TIL, and PD-L1 and their value as prognostic indicators for overall survival (OS) in patients with oropharyngeal squamous cell carcinoma (OPSCC). The results showed that the positivity of p16 and the density of CD8+ TIL were associated with better OS, while the status of PD-L1 was not significantly related to OS. Among the four types of tumor microenvironments (TME), OPSCCs with type I TME (PD-L1+/TIL+) had the best survival outcome.