TP53 and head and neck squamous cell carcinoma: These findings indicate that deregulation or loss of normal TP53 function, the most frequent genomic mutation characterizing HNSCC, may be driving increased TMB that ultimately results in deregulated immune function and impairs the ability to respond to treatment; however, the relationship between the rules of cooperation between these mutations, subsite histology, and clinical outcomes remain incompletely characterized [43,49,50].