We noted that activating PIK3CA mutations appeared to be more frequent in three HPV-positive tumors sequenced by Stransky et al., and we confirmed this finding by sequencing the PIK3CA hotspots in a larger number of HPV-positive (46) and negative (43) oropharyngeal HNSCC samples [17]. The gene discussed is PIK3CA; the disease is head and neck squamous cell carcinoma.