Treatment benefit of regular NSAID exposure for DSS and OS. (A) Model-predicted DSS probability indicates no survival difference between regular users (Yes, blue) versus never or occasional users (No, orange) for HNSCC patients with unaltered PIK3CA. (B) Patients harboring mutated or amplified PIK3CA exhibited a survival advantage with regular NSAID use (Yes, blue). (C) Model-predicted OS probability indicates no survival difference between regular users (Yes, blue) versus never or occasional users (No, orange) for HNSCC patients with unaltered PIK3CA. (D) Patients harboring mutated or amplified PIK3CA exhibited a survival advantage with regular NSAID use (Yes, blue). Dotted vertical reference lines indicate 5 yr of follow-up. P values are based on Z statistics for testing contrasts derived from the design matrix of the selected regression model and are adjusted for HPV status, type of cancer (primary versus recurrence), pathological N stage, and age at surgery (for OS only). Gray bands indicate 95% confidence intervals.