Distinct Molecular Landscape and Clinical Subtype of HPV-Positive Esophageal Squamous Cell Carcinoma

Abstract

Simple Summary Human papillomavirus (HPV) is a well-established cause of several anogenital and oropharyngeal cancers, but its role in esophageal squamous cell carcinoma (ESCC) among Chinese patients remains controversial. We retrospectively analyzed 120 Chinese patients with ESCC and detected HPV DNA in 44.2% of tumors (53/120), predominantly high-risk types such as HPV16 and HPV18. HPV-negative tumors more frequently carried PTEN mutations and exhibited lymphovascular invasion, whereas HPV positivity was associated with a trend toward better recurrence-free survival. These findings suggest that HPV DNA status may delineate subgroups of ESCC with distinct clinicopathological and molecular features and could inform subtype-stratified prevention and treatment strategies; however, the transcriptional activity of the detected HPV and its causal contribution to ESCC require further investigation.