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.