Predictive and prognostic factors for immunotherapy response in head and neck squamous cell carcinoma: a narrative review

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have reshaped the therapeutic landscape of head and neck squamous cell carcinoma (HNSCC). However, only a subset of patients derives durable benefit, highlighting the need for reliable predictive factors of response. AREAS COVERED: A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (2015-2026) using relevant keywords. This narrative review summarizes and categorizes currently available evidence on biological, inflammatory and clinical biomarkers associated with response to immunotherapy in HNSCC, with particular attention to PD-L1 expression, HPV status, tumor mutational burden, immune microenvironment, systemic inflammatory indices and performance status. EXPERT OPINION: PD-L1 expression assessed by Combined Positive Score (CPS) remains the only validated clinical biomarker, although its dynamic and heterogeneous nature limits accuracy. HPV positivity, high tumor mutational burden, favorable immune microenvironment, low neutrophil-to-lymphocyte ratio and good Eastern Cooperative Oncology Group Performance Status (ECOG PS) are consistently associated with improved outcomes. No single marker adequately predicts. Response to immunotherapy in HNSCC is multifactorial. Integrating biological and clinical parameters may support a personalized approach to immunotherapy.