The clinical benefit of immunotherapy in recurrent, metastatic head and neck squamous cell carcinoma has fueled interest in revisiting neoadjuvant approaches to complement definitive treatment. Neoadjuvant strategies incorporating immune checkpoint inhibitors and other novel immune-based therapies in head and neck cancer are reviewed here, with particular attention paid to the rationale for these approaches from both a clinical and biologic discovery standpoint. The potential benefits of neoadjuvant immunotherapy include reduction of extent of surgery and the intensity of adjuvant therapy by tumor downstaging, reduction of the risk of distant metastatic spread by early introduction of systemic therapy, conversion of unresectable to resectable disease, and early evaluation of biomarkers of tumor response. We await early trial results utilizing these approaches to confirm both safety and initial efficacy in head and neck cancer.
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