BACKGROUND: Although studies have demonstrated a relationship between pathogenic microorganisms and oral cancer, no study has demonstrated a relationship between changes in bacterial flora and oral squamous cell carcinoma (OSCC). Therefore, we investigated the association between oral microbiota and oral squamous cell carcinoma using metagenomic analysis. METHODS: Saliva samples from 64 patients with OSCC and 50 healthy controls who visited the Department of Oral Surgery, Tohoku University Hospital, were collected, and bacterial genomic DNA was extracted using polymerase chain reaction amplification. Single-end sequencing was performed using the Illumina MiSeq platform, and sequence data were analyzed using the Quantitative Insights Into Microbial Ecology 2 platform. The Steel-Dwass test was used for between-group comparisons, and Analysis of Compositions of Microbiomes with Bias Correction was used to detect significant differences in microbiome composition. RESULTS: Significant differences were observed in alpha-diversity indices of bacterial flora (richness, Faith- phylogenetic diversity, Shannon index) in the OSCC group compared to those in the control group. Among the OSCC group, patients with larger tumor diameters and lymph node metastases (T3/T4, N1 or greater) formed independent clusters in the beta diversity analysis of the bacterial flora. Bacteria of the Actinomycetia phylum, such as Actinomyces and Rothia, were significantly reduced in patients with higher stage and pathological grade. Conversely, bacteria of the phylum Spirochaetia and Proteobacteria, particularly those of the genus Treponema, were significantly elevated in advanced cancer cases. CONCLUSIONS: Our results suggest that changes in the oral microbiota may play a role in OSCC development and progression.

OBJECTIVE: To clarify the relationship between oral squamous cell carcinoma (OSCC), potentially malignant oral disease (OPMD), and bacterial flora using metagenomic analysis. METHODS: This cross-sectional observational study included 50 patients in the control group and 77 patients with OPMDs, 41 with early OSCCs, and 20 with advanced OSCCs. Patient saliva samples were subjected to high-throughput sequencing of 16S rRNA gene amplicons to evaluate the composition and diversity of the oral microbiome. RESULTS: No significant differences were observed in patient backgrounds, other than sex. Patients with advanced OSCCs had greater oral bacterial diversity than those with early OSCC or OPMD. The advanced OSCC group formed a distinct cluster separate from the other groups. Sixteen and 275 species were identified at the phylum and genus levels, respectively. Compared with the control group, Actinomycetia and Streptococcus were significantly elevated in the early OSCC and OPMD groups. Peptostreptococcus and Fusobacterium were significantly higher in the advanced OSCC group than in the control, OPMD, and early OSCC groups. CONCLUSIONS: The composition and diversity of oral microbiota may be associated with OPMD development and progression to OSCC. Consequently, the salivary microbiome may serve as a biomarker for oral cancer and help predict cancer progression.

MicroRNAs (miRNAs) have attracted attention as non-invasive cancer biomarkers in various cancers; however, they have not been adequately investigated in oral squamous cell carcinoma (OSCC). This study investigated the diagnostic performance of serum-derived miRNAs at initial diagnosis for primary neck lymph node metastasis and the predictive performance for late neck lymph node metastasis based on long-term (up to approximately 8 years) follow-up of patients with OSCC. The expression of miRNAs in 40 patients with OSCC was quantified using real-time PCR (qPCR), and a comprehensive statistical analysis of the correlation of miRNA expression for primary and late neck lymph node metastases was performed. For the diagnosis of primary neck lymph node metastases, miR-423 and miR-125 were accurate. The miRNA index for primary metastasis diagnosis (miR-PM) calculated by regression analysis showed high diagnostic accuracy. The miR-5100 was useful for predicting late neck lymph node metastases. The miRNA index for late metastasis prediction (miR-LM) calculated using regression analysis showed high prediction accuracy. MiRNAs were useful for diagnosing primary neck lymph node metastases in OSCC and predicting late neck lymph node metastases. It may help to consider individualized treatment, including follow-up, surgical methods, and postoperative management.

Few studies have investigated the relationship between nutritional status and comprehensive assessment of oral hypofunction, especially protein intake-related sarcopenia. Thus, we explored these relationships in a large-scale cross-sectional cohort study using the seven-item evaluation for oral hypofunction and Diet History Questionnaire for nutritional assessment. We used the data from 1004 individuals who participated in the 2019 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan for analysis. We found that individuals with oral hypofunction were significantly older with a lower skeletal muscle index. Although there were few foods that had a significant difference between the groups with and without oral hypofunction, the consumption of beans and meats was significantly lower in women and men in the oral hypofunction group, respectively. According to the lower limit of the tentative dietary goal defined in Japan, comprehensive evaluation of oral hypofunction was significantly and independently associated with protein intake in both men and women (odds ratio, 1.70; 95% confidence interval, 1.21-2.35). In conclusion, we found that oral hypofunction was associated with targeted protein intake for sarcopenia and frailty prevention in middle-aged and older community-dwelling adults. Comprehensive evaluation of oral function with intervention in cases of hypofunction could inform clinicians to better prevent sarcopenia.

Oral hypofunction is a new concept that addresses the oral function of older adults. Few studies have investigated the relationship between oral hypofunction and general health conditions such as frailty, sarcopenia, and mild cognitive impairment. This paper explores these relationships in a large-scale, cross-sectional cohort study. The relationships of oral hypofunction with frailty, sarcopenia, and mild cognitive impairment were examined using data from 832 individuals who participated in the 2018 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan. Individuals with frailty, sarcopenia, and mild cognitive impairment had significantly higher rates of oral hypofunction. Frailty was independently associated with deterioration of the swallowing function (odds ratio 2.56; 95% confidence interval, 1.26-5.20), and mild cognitive impairment was independently associated with reduced occlusal force (odds ratio 1.48; 95% confidence interval, 1.05-2.08) and decreased tongue pressure (odds ratio 1.77; 95% confidence interval, 1.28-2.43). There was no independent association found between sarcopenia and oral function. In conclusion, early intervention for related factors such as deterioration of the swallowing function in frailty, reduced occlusal force, and decreased tongue pressure in mild cognitive impairment could lead to the prevention of general hypofunction in older adults.