ASSOCIATION OF ORAL MICROBIOTA AND PERIODONTAL DISEASE WITH LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Evidence of oral microbiota perturbations has been accumulated for lung cancers. This review focused on the oral microbiota alterations in population suffering from lung cancer. In addition, we also discussed conflicting data about the association between oral microbiota dysbiosis and risk of lung cancer. A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. The studies evaluated diversity and abundance of oral microbes in healthy and lung cancer individuals as well as association of periodontal disease and pathogens with lung cancer. Of 3559 studies, 28 included studies were performed in qualitative analysis, and 25 studies were used in meta-analyses for quantitative assessment. Heterogeneity was analyzed by using I² and chi-squared Q test statistics. Statistical analyses were performed by using the RevMan 5.4 software. Compared with the control, lung cancer patients had lower alpha diversity (Shannon: SMD = -0.54; 95% CI, -0.90 to -0.19; P < .01, I2 = 71%). In nested case-control studies, individuals with decreased alpha diversity tended to have an increased risk of lung cancer (observed species: HR = 0.90; 95% CI, 0.85-0.96; P < .01, I2 = 0%; Shannon: HR = 0.89; 95% CI, 0.83-0.95; P < .01, I2 = 0%). Overall, no strong evidence of association of relative abundance with specific oral microbes with lung cancers was found because of inconsistent data. No associations were found between periodontal pathogens and lung cancer risk (red complex: HR = 1.12, 95% CI: 0.42-3.02, P = .82, I2 = 62%; orange complex: HR =1.77, 95% CI: 0.78-3.98, P = .17, I2 = 36%), expect for Fusobacterium nucleatum (HR = 2.27, 95% CI: 1.13-4.58, P = .02, I2 = 0%). The positive association of periodontal disease with lung cancer risk was found (HR = 1.58, 95% CI: 1.25-2.00, P < .001, I2= 0%) with increase of periodontal diseases severity (HR = 2.39, 95% CI: 1.57-3.66, P < .001, I2 = 0%). However, such association was not found in never-smoker participants (HR = 1.00, 95% CI: 0.76-1.31, P = .37, I2= 7%). Lower alpha diversity of oral microbiome may be associated with a greater risk of lung cancer and might serve as a predictive signal of lung cancer risk. There was no strong evidence of relative abundance of oral microbial taxa and periodontal pathogens in lung cancer patients. Fusobacterium nucleatum might be a potential microbial candidate of biomarkers in lung cancer. Periodontal disease may be positively associated with lung cancer risk by confounding of smoking, but not an independent risk factor.