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The current standard of therapy for locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) is limited by toxicity and suboptimal control. The role of immunotherapy (IO) is being evaluated in the LA setting. This review aims to summarize the recent advances and the direction of clinical trials in IO in LA or high-risk HNSCC. Despite negative results in some studies, several early phase trials suggest the feasibility and efficacy of IO-based strategies in LA or high-risk HNSCC. Further refining of patient selection and biomarker development is warranted for successful incorporation of IO in this patient population.…