The Prognostic Potential of PD-L1, PD-1, CD3, CD4, and CD8 Expression in Patients with Head and Neck Cancers Depending on HPV16 Infection

Objective: The aim of this study was to evaluate the expression of PD-L1, PD-1, CD3, CD4, and CD8 in tumor tissues of patients with head and neck squamous cell carcinoma from southern Poland, and to assess their prognostic value in relation to disease-free survival (DFS), taking into account HPV16 status and other clinical, pathological, and demographic factors. Material/Methods: This study included 155 unselected patients with head and neck squamous cell carcinoma (HNSCC) from the southern Poland region, who underwent diagnostic evaluation and surgical treatment. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks were obtained from these centers. The patients were treated at the Maria Skłodowska-Curie National Research Institute of Oncology, Kraków Branch, between 1991 and 2014, with treatment approaches including induction therapy (preoperative), adjuvant therapy (postoperative), or definitive chemoradiotherapy with cisplatin. Protein expression was assessed using immunohistochemistry and quantified (TPS, CPS, H-score). Relationships between expression levels and epidemiological, clinical, and histopathological features were analyzed. Results: The results show that PD-L1 overexpression was associated with worse DFS, whereas overexpression of PD-1, CD3, CD4, and CD8 correlated with improved DFS. These associations were statistically significant in the HPV16-negative subgroup, while no such correlations were found in HPV16-positive patients. In multivariate analysis, independent prognostic factors associated with improved DFS included HPV16 infection, absence of PD-L1 overexpression, overexpression of CD4 and CD8, and combined chemoradiotherapy with cisplatin. Conclusions: These findings confirm the prognostic relevance of PD-L1, PD-1, and T-cell markers in HNSCC, particularly in HPV16-negative patients, and support further research into the use of these biomarkers in personalized treatment strategies.