Recently, PIK3CA mutations have been shown to be predictive of PI3K inhibitor and nonsteroidal anti-inflammatory drug (NSAID) responses in HNSCC, with proven biology demonstrated in PI3K-mutant, PI3K-activated preclinical models of HNSCC and retrospective patient cohorts (Lui et al, 2013; Hedberg et al, 2019). Here, PIK3CA is linked to head and neck squamous cell carcinoma.