Immunohistochemical detection of pepsin in recurrent laryngeal papillomatosis: findings consistent with laryngopharyngeal reflux exposure

Background. Recurrent laryngeal papillomatosis (RLP) is a benign epithelial disease with a relapsing course that often requires repeated interventions and imposes a substantial clinical burden. While human papillomavirus infection is the primary etiologic factor, the marked variability in recurrence suggests that additional cofactors may contribute. Laryngopharyngeal reflux has been proposed as one such cofactor through chronic irritation of the laryngeal mucosa. Objective. To assess pepsin immunoreactivity in RLP specimens and interpret the findings as tissue markers consistent with laryngopharyngeal reflux exposure. Materials and methods. We conducted a retrospective, tissue-based analysis of 32 surgically excised laryngeal papilloma specimens from adult patients with RLP, without a control group. Pepsin immunohistochemistry was performed using a standardized protocol with an anti-pepsinogen C (PGC) antibody. Staining was evaluated semi-quantitatively (score 0–3) and characterized by epithelial and stromal localization. Statistical analysis was descriptive. Results. Pepsin immunoreactivity (score ≥1) was detected in 24/32 cases (75.0%; 95% CI: 57.9–86.7). Positivity was typically granular and cytoplasmic within the epithelium, with stratified involvement and a focal/mosaic distribution. Occasional weak staining was also observed in stromal inflammatory cells and vascular endothelium. Score 0 cases showed no epithelial or stromal staining. Conclusions. In this series, pepsin immunoreactivity was frequently detected in RLP tissue, a pattern consistent with laryngopharyngeal reflux exposure. These findings suggest that reflux-related mucosal injury may be a cofactor in disease persistence and recurrence.