The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms.

OBJECTIVE: This study aimed to explore the potential predictive value of oral microbial signatures for oral squamous cell carcinoma (OSCC) risk based on machine learning algorithms. METHODS: The oral microbiome signatures were assessed in the unstimulated saliva samples of 80 OSCC patients and 179 healthy individuals using 16S rRNA gene sequencing. Four different machine learning classifiers were used to develop prediction models. RESULTS: Compared with control participants, OSCC patients had a higher microbial dysbiosis index (MDI, p < 0.001). Among four machine learning classifiers, random forest (RF) provided the best predictive performance, followed by the support vector machines, artificial neural networks and naive Bayes. After controlling the potential confounders using propensity score matching, the optimal RF model was further developed incorporating a minimal set of 20 bacteria genera, exhibiting better predictive performance than the MDI (AUC: 0.992 vs. 0.775, p < 0.001). CONCLUSIONS: The novel MDI and RF model developed in this study based on oral microbiome signatures may serve as noninvasive tools for predicting OSCC risk.

Associations of Urinary Total Arsenic and Arsenic Species and Periodontitis.

AIMS: Arsenic exposure is a significant global public health concern and has been implicated in endocrine disruption and increased oxidative stress, both of which are crucial pathogenic mechanisms of periodontitis. This study aimed to investigate the association of urinary total arsenic and arsenic species with periodontitis and to further explore the potential mediating roles of sex hormones and oxidative stress indicators. METHODS: Data used in this study were derived from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the US population. In all, 1063 participants with complete data were included in this study. Weighted logistic regression analyses were used to evaluate the relationship between urinary arsenic and periodontitis. Mediation analyses were used to explore the effects of potential mediators on these associations. RESULTS: High concentrations of urinary dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), 2 types of toxic urinary arsenic (TUA2), and 4 types of toxic urinary arsenic (TUA4) were positively related to periodontitis (P < .05). After adjusting for potential confounders, the positive association remained significant (odds ratio, 1.32; 95% confidence interval, 1.01-1.71). Testosterone may partially mediate the relationship between MMA and periodontitis, with mediating effects of 21.78% and 39.73% of the total effect. No significant mediation effect of oxidative stress indicators was found for this relationship. CONCLUSIONS: This study reports a positive association between urinary MMA and periodontitis, and testosterone may mediate this relationship. Our findings serve as a call for action to avoid the deployment of arsenic-containing therapeutic agents as treatment modalities for oral afflictions.

Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones.

OBJECTIVES: To investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association. METHODS: We extracted data from National Health and Nutrition Examination Survey (NHANES) 2009-2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones. RESULTS: Participants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01-1.39; PR = 1.17 for PFNA, 95% CI: 1.02-1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables. CONCLUSIONS: These findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.

The associations of coffee consumption, coffee types, and caffeine metabolites with periodontitis: Results from NHANES 2009-2014.

BACKGROUND: Coffee is one of the world's most popular beverages and is the main dietary source of caffeine for most people. The various molecular effects of caffeine suggest that it may enhance bone loss. The purpose of the present study was to investigate the relationship of coffee, coffee types, and caffeine metabolites with periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Total coffee and different types of coffee consumption were acquired through a 24-h dietary recall. Urinary caffeine metabolites were quantified using high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry (HPLC-ESI-MS/MS). The association of coffee, coffee types, and caffeine metabolites with periodontitis and its severity were assessed using multivariable logistic regression. RESULTS: A total of 3309 eligible participants were included. After adjusting for potential confounding variables, a positive association was observed between coffee consumption (particularly certain types of coffee) and periodontitis. Notably, a positive correlation was also found between total coffee intake and the severity of periodontitis. Additionally, for urinary caffeine metabolites, there was a significant positive association between 1-methyluric acid (1-MU), 1,3-dimethyluric acid (1,3-DMU), 3,7-dimethyluric acid (3,7-DMU), 1,7-dimethylxanthine (1,7-DMX), or 5-actlyamino-6-amino-3-methyluracil (AAMU) and periodontitis, with adjusted odds ratios and 95% confidence intervals of 1.10 (1.02, 1.19), 1.86 (1.05, 3.29), 0.94 (0.90, 0.98), 1.29 (1.03, 1.62), and 1.15 (1.05, 1.26), respectively. CONCLUSIONS: The present study suggests a positive association of coffee intake (especially certain coffee types) and caffeine metabolites (1-MU, 1,3-DMU, 3,7-DMU, 1,7-DMX, and AAMU) with periodontitis and its severity.

Association between plasma trans fatty acids and chronic periodontitis: Results from a nationally representative cross-sectional survey.

BACKGROUND: Trans fatty acid (TFA) consumption has been reported to harbor proinflammatory characteristics and increasing oxidative stress properties, but there has been little research into its association with periodontitis. This study aimed to explore the potential association between TFAs and periodontitis. METHODS: This large population-based study included participants from the National Health and Nutrition Examination Survey (2009-2010). Weighted binary and ordinal logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the relationship between plasma TFAs and periodontitis. RESULTS: A total of 1433 eligible participants, 793 (55.3%) participants with periodontitis and 640 (44.7%) without periodontitis were included. Univariate logistic regression revealed significant associations between plasma trans-11-octadecenoic acid, trans-9-octadecenoic acid, the sum of trans-octadecenoic acids, and the sum of TFAs and periodontitis (all P < 0.01). After controlling for the potential confounders, these four types of TFAs remained significantly associated with periodontitis (the ORs and 95% CIs per interquartile range increase were 1.16 (1.01-1.33), 1.20 (1.03-1.39), 1.18 (1.02-1.35), and 1.17 (1.01-1.35), respectively). Notably, these positive associations were more pronounced among overweight/obese populations. Additionally, plasma trans-9-octadecenoic acid levels were found to be associated with periodontitis severity. CONCLUSIONS: This study suggests a significant positive association between certain plasma TFAs and chronic periodontitis, especially among overweight/obese populations. These findings provide new insights into periodontitis prevention from a dietary perspective.

Self-reported cataract surgery and 10-year all-cause and cause-specific mortality: findings from the National Health and Nutrition Examination Survey.

PURPOSE: To investigate the association of self-reported cataract surgery with all-cause and cause-specific mortality using a large-scale population-based sample. METHODS: Data from the 1999-2008 cycles of the National Health and Nutrition Examination Survey were used. A self-reported history of cataract surgery was considered a surrogate for the presence of clinically significant cataract surgery. Mortality data were ascertained from National Death Index records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for survival were estimated using Cox proportional hazards regression models. RESULTS: A total of 14 918 participants were included in the analysis. During a median follow-up of 10.8 (Interquartile range, IQR, 8.25-13.7) years, 3966 (19.1%) participants died. Participants with self-reported cataract surgery were more likely to die from all causes and specific causes (vascular disease, cancer, accident, Alzheimer's disease, respiratory disease, renal disease and others) compared with those without (all Ps <0.05). The association between self-reported cataract surgery and all-cause mortality remained significant after multiple adjustments (HR=1.13; 95% CI 1.01 to 1.26). For cause-specific mortality, multivariable Cox models showed that self-reported cataract surgery predicted a 36% higher risk of vascular-related mortality (HR=1.36; 95% CI 1.01 to 1.82). The association with other specific causes of mortality did not reach statistical significance after multiple adjustments. CONCLUSIONS: This study found significant associations of self-reported cataract surgery with all-cause and vascular mortalities. Our findings provide potential insights into the pathogenic pathways underlying cataract.

Exosomal hsa_circRNA_047733 integrated with clinical features for preoperative prediction of lymph node metastasis risk in oral squamous cell carcinoma.

BACKGROUND: To evaluate whether exosomal circRNAs could serve as diagnostic biomarkers for the accurate preoperative prediction of lymph node metastasis (LNM) risk in oral squamous cell carcinoma (OSCC) patients. METHODS: A combinative strategy of exosomal circRNAs microarray and qRT-PCR verification was employed to dig LNM-related circRNA signatures. Then, a dynamic nomogram was developed based on candidate circRNAs and preoperative clinical features and the calibration, discrimination, and clinical use of the nomogram were evaluated. RESULTS: According to the microarray, three circRNAs derived from the tumor were associated with preoperative LNM risk, including hsa_circRNA_047733, hsa_circRNA_024144 and hsa_circRNA_403472. The hsa_circRNA_047733 was further verified to be significantly downregulated in patients with LNM (+) as compared with those with LNM (-) (p = 0.007). Patients with the higher expression of hsa_circRNA_047733 showed a lower risk of LNM (multivariate-adjusted OR = 0.22, 95%CI: 0.06-0.83). The bioinformatics prediction showed that hsa_circRNA_047733 might sponge miR-4464/miR-4748 to regulate RPS21 expression. A dynamic nomogram integrating exosomal hsa_circRNA_047733 with five clinicopathological characteristics (tumor site, leukocyte level, maximum tumor diameter, and LNM reported by MRI and preoperative biopsy differentiation) was developed. The model displayed an excellent discrimination ability (AUC = 0.868, 95%CI: 0.781-0.955) and great calibration. The decision curve revealed a higher net benefit superior to the baseline model at an 80% threshold probability. CONCLUSION: The data provide preliminary evidence that exosomal hsa_circRNA_047733 might be a novel biomarker for the LNM of OSCC. The hsa_circRNA_047733-based dynamic nomogram could serve as a convenient preoperative assessment tool to predict the risk of LNM for OSCC patients.

Effect of transoral laser microsurgery vs open partial laryngectomy on the prognosis of patients with early laryngeal carcinoma: propensity score-based analysis.

OBJECTIVE: To evaluate the effect of surgical procedures (transoral laser microsurgery (TLM) and open partial laryngectomy (OPL)) on the prognosis of patients with early laryngeal cancer. METHODS: A total of 760 patients diagnosed with early laryngeal cancer (T1-2N0M0) and treated with TLM (n = 416) or OPL (n = 344) between 2004 and 2015 were abstracted from the SEER database. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (SIPTW) were performed to obtain comparable cohorts. The survival rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. Univariate and multivariate Cox regression analyses with a false discovery rate (FDR) correction were applied to contrast the association between two surgical approaches and overall survival (OS) and disease-specific survival (DSS). RESULTS: The 5-year OS for the TLM group was 79.5% versus 77.7% for the OPL group (P = 0.619). Similar results were revealed for the comparison of 5-year DSS rates (91.1% versus 91.5%, P = 0.891). After PSM and SIPTW balance the confounding factors, no significant difference was observed in the OS and DSS of patients treated with TLM compared to patients treated with OPL. The consistent results were still yielded (all P > 0.05), when stratified by gender, age, year of diagnosis, residence, household income, tumor site, T stage, differentiation, and adjuvant therapy. CONCLUSION: This study provides strong evidence that there is no significant difference in the prognosis of early laryngeal carcinoma between the treatment of TLM and OPL, which may be helpful to guide the clinical decision-making of these patients.

Combined Exposure to 33 Trace Elements and Associations With the Risk of Oral Cancer: A Large-Scale Case-Control Study.

Background: Trace elements exist widely in the natural environment and mostly enter the human body through drinking water or various types of food, which has raised increasing health concerns. Exposure to a single or a few trace elements has been previously reported to be associated with oral cancer risk, but studies on other elements and combined effects are limited. This study aimed to comprehensively evaluate the independent and joint effects of 33 trace elements on oral cancer risk. Methods: The concentrations of 33 trace elements from the serum samples of 463 cases and 1,343 controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Propensity score matching was used to minimize the impact of potential confounders. Conditional logistic regression was utilized to evaluate the association of each element individually with oral cancer risk. Quantile g-computation and Bayesian kernel machine regression (BKMR) models were used to assess the joint effect of the overall element mixture and interactions. Results: In single-element models, essential elements (Cu, Se, Zn, Sr, and Cr) and non-essential elements (As, Li, Th, Ce, Ti, and Sc) showed significant association with oral cancer risk. In multiple-element models, a quartile increase in overall non-essential elements was observed for a significant inverse association with oral cancer risk (ß = -3.36, 95% CI: -4.22 to -2.51). The BKMR analysis revealed a potential beneficial joint effect of essential metals on the risk of oral cancer. Among these, higher levels of serum Zn and V exhibited an adverse effect, while serum Sr, Se, and Cu displayed favorable effects when all other essential elements were fixed at 25th or 50th percentiles. Of note, Se performed complex interactions among essential metals. As for non-essential elements, there were greater effect estimates for serum Th, Li, and Y when all other elements were held at the 75th percentile. Conclusion: This study provides supportive evidence that the overall mixture effect of essential and non-essential elements might be associated with oral cancer risk, especially for serum Zn, V, Cu, Sr, Se, Th, Li, and Y. Extensive prospective studies and other experiments are warranted to confirm our findings.

Oolong Tea Consumption and the Risk of Oral Squamous Cell Carcinoma: A Propensity Score-Based Analysis in Southeast China.

Oolong tea is one of the world's most popular non-alcoholic beverages, particularly in coastal Southeast China. Hitherto, epidemiological studies on the association between oolong tea consumption and the risk of patients with oral squamous cell carcinoma (OSCC) are very limited. This study aimed to evaluate the potential effect of oolong tea consumption on OSCC risk in Southeast China. From January 2010 to October 2020, face-to-face interviews were conducted for 744 newly diagnosed OSCC patients and 1,029 healthy controls to collect information on demographics, oolong tea consumption behaviors, and other lifestyle factors. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and stabilized inverse probability of treatment weight (SIPTW) were utilized to minimize confounding effects. Multivariate, conditional, and weighted logistic regression was used to evaluate the associations of oolong tea consumption behaviors with OSCC risk. Participants who drank oolong tea showed a lower risk of OSCC when compared to their non-drink counterparts [PSM population, OR (95%CI): 0.69 (0.49-0.97); SIPTW population, OR (95%CI): 0.74 (0.58-0.94)]. Moreover, the reduced risk was found to be significantly associated with certain tea-drinking habits (consumed amount over 500 mL per day, a duration of <20 years, age at initiation older than 30 years, and warm and moderately concentrated tea). Similar results were yielded in the sensitivity analyses (Multivariate adjustment and the IPTW analysis). Furthermore, subgroup analysis revealed that the negative association of oolong tea drinking with OSCC risk was more evident among those with poor oral hygiene. This study provides supportive evidence that oolong tea consumption may have a potentially beneficial effect in preventing OSCC, especially for those with poor oral hygiene.

U-Shaped Relationship of Rare Earth Element Lanthanum and Oral Cancer Risk: A Propensity Score-Based Study in the Southeast of China.

As an important rare earth element (REE) extensively applied to industry, agriculture, and medicine, lanthanum (La) has attracted a host of health concerns. This study aimed to explore the relationship between La exposure and the risk of developing oral cancer through a case-control study with a large sample size. Serum La levels of 430 oral cancer patients and 1,118 healthy controls were detected by inductively coupled plasma mass spectrometry (ICP-MS). The association of La level with the risk of oral cancer was assessed in two ways: (1) as a continuous scale based on restricted cubic splines (RCS); (2) as a priori defined centile categories using multivariate logistic regression model, based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The RCS revealed a non-linear U-shaped relationship between serum La and oral cancer risk. Serum La deficiency or excess was associated with an increased risk of oral cancer. When the La level was analyzed as a categorical variable, a similar U-shaped association was observed. Of note, compared to those with La concentrations of 0.243-0.341 µg/L (reference quantiles, 41st-60th), the risk was increased in those with the lower or higher quantiles (0.132-0.242 µg/L vs. 0.243-0.341 µg/L: OR = 1.80, 95%CI: 1.07-3.02; 0.342-0.497 µg/L vs. 0.243-0.341 µg/L: OR = 2.30, 95%CI: 1.38-3.84). The results were generally consistent with the PSM and IPTW analyses. This preliminary study provides strong evidence that there was a U-shaped relationship between serum La levels and oral cancer risk. Much additional work is warranted to confirm our findings.

A composite oral hygiene score and the risk of oral cancer and its subtypes: a large-scale propensity score-based study.

OBJECTIVE: This study aimed to investigate the potential relationship between oral hygiene and the risk of oral cancer and its subtypes after controlling the effects of several confounding factors. MATERIALS AND METHODS: A large-scale case-control study was conducted from January 2010 to August 2019, recruiting a total of 1,288 oral cancer cases with newly diagnosed and 4,234 healthy controls. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to minimize confounding effects. Conditional logistic regression was used to evaluate the effects of oral hygiene indicators on oral cancer. RESULTS: A composite oral hygiene score was developed based on five indicators selected based on PSM and IPTW analysis (including tooth loss, dentures wearing, the frequency of tooth brushing, regular dental visits, and recurrent dental ulcer). Participants with a higher score, compared with their lower counterparts, showed a 49% increased risk (the odds ratio (OR) was 1.49 (95% confidence interval (CI): 1.26-1.75). A similar association pattern was found following IPTW analyses (OR = 1.32; 95% CI: 1.22-1.42). Of note, the adverse effects of poor oral hygiene were more evident among the sites of gingival and buccal (PSM analysis: 2.03-fold and 2.68-fold increased risk; IPTW analysis: 1.57-fold and 2.07-fold increased risk, respectively). Additionally, a greater positive association was observed between poor oral hygiene and oral squamous cell carcinoma, compared with other pathological types. CONCLUSION: This study establishes a composite oral hygiene score and provides supportive evidence of poor oral hygiene associated with a higher risk of oral cancer, particularly in the gingival and buccal mucosa sites and in the squamous cell carcinoma. CLINICAL RELEVANCE: The data highlights the importance of improving poor oral hygiene habits, which has public health implications for the prevention of oral cancer.