This study investigates the activation status of the PI3K-AKT-mTOR pathway and its association with PD-L1 expression in oral squamous cell carcinoma (OSCC). Nevertheless, how this pathway interacts with PD-L1 and influences OSCC outcomes has received limited attention.

We retrospectively analyzed data from 80 patients who underwent curative-intent surgery for primary OSCC at a single tertiary center between January 2021 and December 2023. Tumor and normal tissues underwent staining for four markers (p-PI3K, p-AKT, p-mTOR, PD-L1). Marker-clinicopathologic links were analyzed. Survival: Kaplan-Meier + log-rank; independent predictors: multivariate Cox.

Tumor positivity: p-PI3K 58.8%, p-AKT 62.5%, p-mTOR 51.3% (all > normal, P < 0.001). All three linked to advanced stage and nodal spread ( P < 0.05); p-PI3K and p-AKT also tied to poor differentiation. PD-L1: 41.3% positive. p-AKT strongly correlated with PD-L1 ( r = 0.352, P = 0.001), PD-L1 in 54.0% of p-AKT+ vs 20.0% of p-AKT- patients ( P = 0.004). Each marker predicted shorter survival on univariate analysis. Multivariate independent predictors: p-AKT (HR = 2.156) and nodal metastasis (HR = 2.458).

OSCC tumors frequently activate this pathway, which tracks with aggressive behavior. The dual association of p-AKT positivity with poor survival and PD-L1 overexpression suggests its potential utility in stratifying patients for regimens combining targeted therapy with immune checkpoint blockade.