The study also reports the prevalence of canonical PIK3CA gene mutations (substitutions for H1047L and E542K, E545K, and E545D) within an HNSCC Portuguese patient series at the time of diagnosis and conducted an exploratory analysis to test the hypotheses: (1) whether PIK3CA (canonical) mutations are associated with HPV-positive HNSCC, as evaluated by HPV DNA and p16INK4a and (2) whether PIK3CA mutations are independently associated with overall and disease-free survival. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.