Given recent work by our group that correlated CYLD mutations in HPV-positive basaloid carcinomas of the anus with cylindroma-like histologic features, low tumor mutational burden (TMB), and low frequency of PIK3CA driver mutations [16], we hypothesized that CYLD-mutant, HPV-positive HNSCCs may have similarly distinctive histologic and genomic features. Here, PIK3CA is linked to neoplasm.