We conducted comparative transcriptomic analysis of this patient’s tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. The gene discussed is MYC; the disease is head and neck squamous cell carcinoma.