Oral Health and Risk of Liver Cancer: Evidence from Pooled and Meta-Analyses

Abstract

Background: Poor oral health, including periodontal disease and tooth loss, is linked to systemic inflammation and oral microbial dysbiosis, which may promote liver carcinogenesis through the oral-gut-liver axis. However, epidemiologic evidence on oral health and liver cancer risk remains inconsistent. We examined these associations in three prospective US cohorts and conducted a systematic review and meta-analysis of prospective studies. Methods: We pooled data from the Health Professionals Follow-Up Study, Nurses’ Health Study, and Women’s Health Initiative (230,915 participants, 198 liver cancer cases). Oral health, including periodontal disease and tooth loss, was self-reported. Multivariable-adjusted Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). A systematic review through September 2025 identified four additional prospective studies, which were combined with pooled results in meta-analyses. Results: In the pooled analyses, periodontal disease (HR=0.99, 95%CI: 0.67–1.47) and complete tooth loss (HR=1.29, 95%CI: 0.71–2.35) were not associated with liver cancer risk. In the meta-analysis, dominated by one large study, periodontal disease was associated with an increased liver cancer risk (HR=1.08, 95%CI: 1.03-1.13; n=4 studies; I2=0.0%). In a linear dose-response meta-analysis, complete tooth loss was associated with an increased risk (HR=1.32, 95%CI: 1.06-1.66; n=6; I2=0.0%). Conclusions: The findings of the current investigation suggest that while an association between oral health and liver cancer is possible, the results remain inconclusive. Impact: These findings underscore the need for more studies using harmonized oral health assessments integrating clinical, microbial, and behavioral data to better capture oral health burden.