However, a recent report using larger number of patients and more robust methodologies, including the use of surrogate markers such as TP53 mutations and CKI (cyclin-dependent kinase inhibitor) 2A (p16) overexpression, have shown that HPV presents a minor role, if any, in ESCC development [35–37]. This evidence concerns the gene CDKN2A and esophageal squamous cell carcinoma.