Abstract
Helicobacter pylori (H. pylori) colonization in the oropharynx has been suggested to contribute to the development of head and neck squamous cell carcinoma (HNSCC), but prospective evidence remains limited. This prospective cohort study aimed to investigate the association between oropharyngeal H. pylori colonization, including its virulence gene types, and the risk and prognosis of HNSCC. A total of 220 high-risk individuals and 220 diagnosed HNSCC patients were enrolled. Oropharyngeal samples were collected for H. pylori detection by culture and quantitative PCR (qPCR). Virulence genes cagA and vacA were genotyped. Cox proportional hazards models assessed HNSCC incidence and overall survival, with Kaplan–Meier and log-rank tests evaluating survival differences. H. pylori positivity was significantly higher in the HNSCC group compared to the high-risk group (43.6% vs. 32.7%, P = 0.033). In high-risk individuals, H. pylori colonization was an independent risk factor for HNSCC onset (HR = 1.50, 95% CI: 1.02–2.21, P = 0.039), with higher bacterial loads and presence of high-virulence genotypes (e.g., cagA+/vacA s1/m1) linked to increased risk (P < 0.05). Among HNSCC patients, H. pylori-positive individuals showed higher recurrence (26.0% vs. 16.9%, P = 0.018) and mortality rates (13.5% vs. 8.1%, P = 0.043), with poorer overall survival (HR = 1.57, P = 0.035). Co-infection with HPV may further complicate the clinical profile, potentially involving the local immune microenvironment. Oropharyngeal H. pylori colonization, particularly by high-virulence strains, significantly elevates the risk of HNSCC development and worsens clinical outcomes. The interplay between H. pylori and HPV suggests the need for integrated pathogen screening and targeted interventions to improve early detection and individualized treatment strategies for HNSCC.