The Henderson et al. (2014) analysis reported these helical domain substitutions to be HPV+ HNSCC-specific based on correlations between APOBEC3B expression, and HPV status and the prevalence of TCW→TKW substitutions, yet it appears that the cancer effect size of these mutations is substantial in both HPV– HNSCC and HPV+ HNSCC. This evidence concerns the gene APOBEC3B and head and neck squamous cell carcinoma.