Immunotherapy and Targeted Therapy for Head and Neck Squamous Cell Carcinoma: Current Evidence and Future Directions

AbstractImmunotherapy and targeted therapy have transformed the management of head and neck squamous cell carcinoma (HNSCC), particularly in recurrent and/or metastatic disease. Immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab demonstrate durable responses in selected patients, while targeted agents—including epidermal growth factor receptor (EGFR) inhibitors, vascular endothelial growth factor (VEGF)/angiogenesis inhibitors, and antibody-drug conjugates (ADCs)—offer additional therapeutic avenues. This review synthesizes current evidence from pivotal clinical trials, discusses biomarker-driven treatment selection, and outlines future research directions essential for postgraduate learners and clinicians. With updated results from KEYNOTE-048 demonstrating sustained survival benefits at 4-year follow-up, pembrolizumab with or without chemotherapy remains the standard of care in first-line recurrent/metastatic HNSCC. Emerging strategies combining immunotherapy with radiotherapy, targeted agents, and novel ADCs show promise for overcoming resistance and improving outcomes.