Because high p16 expression (encoded by CDKN2A) expression is a surrogate biomarker for HPV-related HNSCC [53] and associated with prognosis [54], we hypothesize that the lack of AP-2alpha response to EGFR inhibition in HPV-positive HNSCC are due to that fact that HPV-positive tumors may not be dependent on EGFR, but likely driven by viral oncoproteins, E6 and E7. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.