Avincsal MO, et al. - A small subset (7%) of esophageal squamous cell carcinomas completely lacking SOX2 expression have unique clinicopathologic features and a dismal prognosis. The purpose of the current study was to determine if the findings obtained in esophageal cancers are applicable to hypopharyngeal (HPSCCs) or oropharyngeal squamous cell carcinomas (OPSCCs). It was shown that a small subset (8%) of HPSCCs lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates, which was similar to esophageal cancers. In addition, promoter hypermethylation was shown to be a major mechanism underlying epigenetic SOX2 silencing.