Esophageal Squamous Papilloma: Clinicopathological Features and p16 Immunoexpression Patterns

Objective: This study aimed to characterize the clinicopathological features of esophageal squamous papilloma (ESP) and to evaluate p16 immunoexpression patterns and their associations with clinicopathological findings. Reflux-related findings, Helicobacter pylori, and follow-up outcomes were also investigated. Methods: Sixty-five patients with histopathologically confirmed ESP between January 2009 and August 2020 were retrospectively evaluated. Clinical and endoscopic data were recorded, and specimens were re-evaluated. p16 immunohistochemical staining was classified as negative, focal/patchy, or block type. Helicobacter pylori in ESP tissue was assessed using Giemsa staining. Results: Among 46 264 upper gastrointestinal endoscopies performed during the study period, ESP prevalence was 0.14%. Median age was 45 years and 50.8% were female. Lesions were solitary in 86.2%, located in the mid-esophagus in 67.7%, and had a median diameter of 3 mm. No case showed block-type p16 expression; focal/patchy staining was observed in 18.5%. No significant association could be demonstrated between p16 expression pattern and clinicopathological characteristics. Reflux symptoms and endoscopic esophagitis were significantly associated with histological inflammation. Helicobacter pylori was detected in 15.4% of cases. Among 9 patients with endoscopic follow-up, 1 recurrence occurred, with no new dysplasia or squamous cell carcinoma. Conclusion: Esophageal squamous papilloma is a rare, predominantly small, solitary lesion with a predilection for the mid-esophagus. Block-type p16 expression was absent, while focal/patchy expression was not associated with any of the clinicopathological characteristics examined, although the small number of positive cases limits the power of these comparisons. Associations of reflux symptoms and endoscopic esophagitis with histological inflammation support a possible role for chronic mucosal irritation; however, the mid-esophageal predominance suggests that reflux alone does not explain ESP development. Cite this article as: Günler T, Karanis MIE. Esophageal squamous papilloma: clinicopathological features and p16 immunoexpression patterns. Cerrahpaşa Med J 2026, 50, 0136, doi: 10.5152/cjm.2026.26136.