A previous study found that HPV-positive EAC harbored approximately 50% fewer nonsilent somatic mutations than HPV-negative EAC.8 Moreover, TP53 aberrations are less frequent in HPV-positive BD and EAC compared with viral-negative esophageal lesions.7,8,9 Prior studies from our group have also demonstrated that HPV-positive BD and EAC are mostly wild-type TP53. 7,9 In this study, we similarly found that only a quarter of HPV-positive HGD and EAC lesions harbored TP53 mutations vs two-thirds of HPV-negative HGD and EAC having the same molecular aberration. The gene discussed is TP53; the disease is esophagitis.