Only a handful of HNSCC studies have applied genome-wide CRISPR cas9 screening: two mapped core essential genes; two mapped cisplatin resistance and radiation resistance; and others uncovered synthetic-lethal targets, including vulnerabilities to mTOR inhibition, EGFR inhibition, glutamine metabolism inhibition, and host determinants of oncolytic HSV-1 efficacy. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.