These agents are approved by the US Food and Drug Administration for recurrent or metastatic HNSCC.4,5,6 More recently, the phase 3 KEYNOTE-689 trial demonstrated that neoadjuvant and adjuvant pembrolizumab significantly improved event-free survival in patients with locally advanced HNSCC.7 On this basis, pembrolizumab has been approved for the first-line treatment for patients with resectable, locally advanced HNSCC whose tumor expressed programmed cell death 1 ligand 1, signaling a paradigm shift in standard of care. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.