Noticeably, percentages of NSD1 and PIK3CA mutations as well as TP63 amplification were significantly higher in the atypical and classical subtypes between HPV-negative HNSCC (P = 0.0013, P = 0.0003, and P = 0.0002, respectively), whereas the percentage of CCND1 amplification was not different between the four subtypes (P = 0.7130) (Fig. 4c). Here, PIK3CA is linked to head and neck squamous cell carcinoma.