Helicobacter pylori Infection Is Associated With the Occurrence and Progression of Vocal Fold Leukoplakia via NRF2 / KEAP1 Pathway Activation

Helicobacter pylori ( H. pylori ) infection has been implicated in vocal fold leukoplakia (VFL), a precancerous laryngeal lesion. However, the underlying mechanisms remain unclear. This study investigated the relationship between H. pylori and VFL, focusing on the NRF2/KEAP1 oxidative stress pathway. Clinicopathological analysis was performed on samples from 64 patients with VFL and 30 patients with vocal cord polyps (controls). The results showed a significantly higher prevalence of H. pylori in the VFL group (48.4%) than in the controls (16.7%, p = 0.003). Among H. pylori ‐positive VFL cases, VacA‐positive strains predominated, accounting for 71.0%. Multivariate logistic regression identified H. pylori as an independent risk factor for VFL (OR = 6.198, 95% CI: 1.580–24.321). VFL tissues exhibited upregulated expression of NRF2, KEAP1, and HO‐1 ( p < 0.001), demonstrating both virulence‐dependent (HO‐1 induction) and virulence‐independent (NRF2 upregulation) pathway activation patterns. In vitro experiments revealed that H. pylori exposure induced NRF2 nuclear translocation and triggered an oxidative stress response. Notably, VFL‐derived cells responded more rapidly to H. pylori stimulation, with pathway activation peaking at 24 h post‐infection, whereas normal cells showed a delayed response, peaking at 48 h ( p < 0.05). Furthermore, VFL‐derived cells displayed more pronounced stress‐induced morphological alterations following H. pylori exposure. These findings suggest that H. pylori may promote VFL progression via NRF2/KEAP1 pathway activation, highlighting the potential clinical value of H. pylori screening in VFL management.