TP53 and head and neck squamous cell carcinoma: In summary, MPSTs have revealed a complex molecular landscape in HNSCC, as many different driver genes are present in small fractions of different tumors, which enhances the effect of more commonly involved genes, such as TP53 and CDKN2A. MPSTs have highlighted the role of previously unreported or underrepresented genes, such as PIK3CA, NOTCH family genes, FBXW7, and many others to a lesser extent.