Efficacy and Safety of Neoadjuvant Immunochemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

OBJECTIVE: Conventional neoadjuvant chemotherapy yields limited benefits for locally advanced head and neck squamous cell carcinoma (LA-SCCHN) patients. Emerging neoadjuvant immunochemotherapy (ICT) holds potential; however, existing evidence remains conflicting. This study systematically evaluated the efficacy and safety of neoadjuvant ICT in this cohort. METHODS: In accordance with PRISMA guidelines, a systematic literature search was performed in PubMed, Web of Science, MEDLINE, and Scopus from inception to July 2025. Cochrane and Joanna Briggs Institute tools were used for bias assessment. The primary endpoints were pathologic complete response (pCR), major pathologic response (mPR), and CR; secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3 to 4 adverse events. RESULTS: Nine studies involving 2507 patients were included. Neoadjuvant ICT significantly improved pCR (6.90% vs. 1.46%; OR=6.07, 95% CI:2.39-15.43; P=0.0002), CR (47.99% vs. 33.14%; OR=2.52, 95% CI:1.29-4.91; P=0.007), and ORR (83.51% vs. 80.04%; OR=2.03, 95% CI:1.17-3.52; P=0.01), with no significant differences in OS, PFS, mPR, or DCR. Grade ≥3 adverse events were more frequent in the neoadjuvant ICT group (56.34% vs. 47.96%; OR=1.32, 95% CI:1.09-1.61; P=0.005). CONCLUSION: Neoadjuvant ICT enhances short-term pathologic and tumor responses in LA-SCCHN versus neoadjuvant chemotherapy, but increases toxicity and lacks proven survival benefits. Further high-quality trials are needed to optimize ICT regimens and identify predictive biomarkers.