Advances in neoadjuvant therapy for locally advanced head and neck squamous cell carcinoma (Review)

The majority of head and neck cancers arise from the mucosal squamous epithelium of the oral cavity, pharynx and larynx, and are collectively referred to as head and neck squamous cell carcinoma (HNSCC). A multimodal standard of care is applied for case management. Primary oral cavity cancers are treated with resection followed by adjuvant cisplatin‑based chemoradiotherapy (CRT), and definitive concurrent CRT is applied for pharyngeal or laryngeal disease. In human papillomavirus‑negative patients who are medically unfit for platinum treatment, the epidermal growth factor receptor‑directed monoclonal antibody cetuximab is administered concomitantly with radiotherapy (RT). More recently, immune checkpoint inhibitors (ICIs) have redefined systemic therapy for recurrent/metastatic HNSCC, yielding durable responses and a survival benefit. In total, 65‑70% of patients present with stage III‑IVA locally advanced (LA) disease, a scenario associated with therapeutic challenges and a marked deterioration in the quality of life. Neoadjuvant therapy is designed to downstage the primary tumor, eradicate occult micrometastatic disease and enhance locoregional control before definitive surgery or RT, thus offering a rational strategy for organ preservation. Contemporary regimens integrate taxane, platinum and 5‑fluorouracil induction chemotherapy with RT, and early‑phase trials have explored the feasibility and efficacy of incorporating ICIs into neoadjuvant protocols. The present review summarizes the evolution of neoadjuvant therapy for LA HNSCC, with particular emphasis on emerging immunotherapy‑based paradigms and their potential to improve oncological and functional outcomes.