Immunotherapeutic Approaches to Head and Neck Squamous Cell Carcinoma: Current Clinical Practice and Future Directions.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is frequently diagnosed at advanced stages and has historically been associated with poor outcomes. Immune checkpoint inhibition has transformed the therapeutic landscape, offering durable responses in recurrent, metastatic, and locally advanced disease. This review summarizes pivotal clinical trials evaluating immunotherapeutic strategies in HNSCC, including PD-1/PD-L1 inhibitors, combination regimens, and emerging modalities across recurrent/metastatic and curative-intent settings, with attention to efficacy, safety, and biomarkers. Phase III trials have established pembrolizumab and nivolumab as standards of care in recurrent or metastatic HNSCC, demonstrating improved overall survival and favorable toxicity profiles. Recent studies support earlier integration of immunotherapy, including neoadjuvant and adjuvant approaches, with meaningful gains in event-free and disease-free survival. Immunotherapy is reshaping the management of HNSCC. Ongoing trials, biomarker refinement, and novel strategies are expected to further expand benefit and personalize treatment.