Specifically, HPV− HNSCC tumors often present with PIK3CA, TP53, and CDKN2A alterations [13], while HPV+ HNSCC tumors have been shown to exhibit PIK3CA, TRAF3, CYLD, and E2F1 alterations [2, 15]. Here, CDKN2A is linked to head and neck squamous cell carcinoma.