The correlation between FDG-PET metabolic parameters, PD-L1 expression and p16/HPV status in oropharyngeal cancers

Immunotherapy targeting the PD-1/PD-L1 axis has emerged as a promising strategy in oropharyngeal squamous cell carcinoma (OPSCC). However, reliable non-invasive biomarkers to predict immune checkpoint expression and treatment response are still lacking. This study aimed to investigate the relationship between PET/CT-derived metabolic parameters, PD-L1 expression, and p16/HPV status, and their prognostic value in OPSCC. In this retrospective analysis, 60 patients with newly diagnosed OPSCC who underwent baseline 18F-FDG PET/CT were included. Tumor PD-L1 expression was assessed using both Tumor Proportion Score (TPS) and Combined Positive Score (CPS). Correlations were analyzed between metabolic PET/CT parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) and PD-L1 expression. Correlation analyses, survival outcomes, and response to chemoradiotherapy were evaluated, with subgroup analyses based on p16 and HPV DNA status. Significant positive correlations were observed between volumetric PET/CT parameters and PD-L1 expression. In HPV DNA-positive OPSCC, PET/CT-derived volumetric parameters (MTV and TLG) showed positive correlations with PD-L1 expression (TPS: rho = 0.501 and 0.512; CPS >20: rho = 0.441 and 0.491). Higher MTV and TLG were associated with significantly shorter overall survival (p = 0.005 and p = 0.001, respectively). Multivariate Cox regression showed the strong prognostic effect of TLG, independent of p16, MTV and even primary tumor stage. Staging MTV was found to be an independent predictor of complete response to chemoradiotherapy (p = 0.026, OR (odds ratio) = 1.08). (No significant correlation was found in the p16-negative subgroup.) Metabolic tumor burden, reflected by PET/CT-derived MTV and TLG, is positively associated with PD-L1 expression and clinical outcomes in OPSCC. These findings suggest a biologically meaningful link between tumor glycolytic activity and immune checkpoint regulation, particularly in HPV-associated cases. PET/CT-based metabolic profiling may serve as a non-invasive tool for risk stratification and immunotherapy planning in OPSCC.