Esophageal papillomas and human papillomavirus infection: A case series, scoping review and analysis

Human papillomaviruses (HPVs) have been implicated in the development of papillomatous proliferations in the esophagus. In 2013, the HPV detection rate in esophageal squamous papillomas (ESPs) was estimated at 30.9%. However, the current prevalence of ESPs and the contemporary HPV-positivity rate remain unclear. Esophageal papillomatosis was proposed as an exceedingly rare entity, distinct from ESPs.

This study includes three novel cases with extensive esophageal proliferations, including one case with esophageal papillomatosis, and an updated scoping review of ESP and esophageal papillomatosis cases reported between 2013 and 2025. The main objective was to synthesize the available evidence on potential associations between esophageal papillomatous proliferations, HPV infection and malignant transformation.

A total of 911 patients with ESP and esophageal papillomatosis were identified, comprising 869 adults and 42 children. The overall HPV detection rate was 11.7%, lower than reported previously. HPV-positivity was lowest in solitary ESPs (6.9%), higher in multiple ESPs (14.8%), and highest in extensive esophageal papillomatosis (21.4%). Dysplastic and malignant features were observed in 0.8% and 1.4% of the solitary and multiple ESPs, respectively, and were most frequent in esophageal papillomatosis (25.9%). A significant association was found between HPV-positivity and dysplasia or malignancy (p = 0.001963).

HPV-positivity appears to increase with the extent of papillomatous disease and is highest in esophageal papillomatosis. Although rare, HPV-associated esophageal dysplasia and malignancy may occur, particularly in esophageal papillomatosis. In cases with confirmed HPV infection and extensive disease, timely intervention - e.g., by endoscopic mucosal resection - may represent a pro-active, therapeutic strategy.