The emerging role of neoadjuvant immunotherapy in locally advanced oral squamous cell carcinoma: progress and challenges

The management of locally advanced oral squamous cell carcinoma (LAOSCC) continues to pose significant challenges. Although surgery combined with adjuvant radiotherapy or chemoradiotherapy remains the standard treatment modality, the 5-year overall survival rate for LAOSCC patients is only approximately 50%. Neoadjuvant therapy aims to reduce tumor burden, improve surgical resectability, and decrease distant metastasis risk, yet its clinical value in LAOSCC has not been fully established. In recent years, the remarkable survival benefits demonstrated by immune checkpoint inhibitors in recurrent/metastatic head and neck squamous cell carcinoma have spurred exploration of neoadjuvant immunotherapy (NAIT). However, the efficacy and safety profile of NAIT in LAOSCC still require systematic evaluation. This review synthesizes current evidence and challenges regarding neoadjuvant therapeutic strategies for LAOSCC, encompassing chemotherapy, chemoradiotherapy, targeted therapy, and immunotherapy (as monotherapy or combination regimens), while examining their implications for clinical practice.