Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer.

BACKGROUND: We previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary biomarkers for oral squamous cell carcinoma (OSCC) and developed a sensitive ELISA for MMP-1 with good performance in detection of OSCC using a cohort of 1160 saliva samples. METHODS: A time-saving rapid strip test (RST) for MMP-1 was developed in this study and its diagnostic performance compared with ELISA using saliva samples from a new cohort of 603 subjects (171 healthy controls, 236 patients with oral potentially malignant disorders, and 196 OSCC patients). RESULTS: Salivary MMP-1 levels measured using RST and ELISA were highly comparable and both assays could effectively distinguish between OSCC and non-cancerous groups. Similar to ELISA, receiver operating characteristic curve analysis of the MMP-1 RST was effective in identifying patients with OSCC at different oral cavity sites and stages. CONCLUSIONS: Salivary MMP-1 can be sensitively detected using both RST and ELISA methods. Our newly developed point-of-care MMP-1 RST is a promising in vitro diagnostic device (IVD) that may serve as a novel auxiliary tool in the routine clinical detection and monitoring of OSCC.

Electro-optic properties of liquid crystal cells with nanowall electrodes.

This work fabricates a nanowall electrode for achieving advanced liquid crystal (LC) devices and improving LC displays. The nanowall electrode consists of indium-tin-oxide (ITO) sheets stacked with nanowalls, and the nanowalls have a height and thickness of 4 µm and 500 nm, respectively. The high aspect ratio (8.0) of the nanowalls sets the nanowall electrode apart from previous electrodes. A flat electrode that comprises only ITO sheets is used to evaluate the nanowall electrode. The LC cell with the nanowall electrode exhibits better electro-optic properties than the LC cell with the flat electrode due to the strong transverse electric field and small subelectrode gap of the nanowall electrode. Especially, the operating voltage (3.7 V) of the nanowall cell is 36% smaller than that (5.8 V) of the flat cell. Therefore, nanowall electrodes have potential in LC lenses, LC antennas, metaverse displays, and digital optics.

Phocaeicola oris sp. nov., an anaerobic bacterium isolated from the saliva of a patient with oral squamous cell carcinoma.

A Gram-stain-negative or -positive, strictly anaerobic, non-spore-forming and pleomorphic bacterium (designated 14-104T) was isolated from the saliva sample of a patient with oral squamous cell carcinoma. It was an acid-tolerant neutralophilic mesophile, growing at between 20 and 40 °C (with optimum growth at 30 °C) and pH between pH 3.0 and 7.0 (with optimum growth at pH 6.0-7.0). It contained anteiso-C15 : 0 and C15 : 0 as the major fatty acids. The genome size of strain 14-104T was 2.98 Mbp, and the G+C content was 39.6 mol%. It shared <87 % 16S rRNA sequence similarity, <71 % orthologous average nucleotide identity, <76 % average amino acid identity and <68 %% of conserved proteins with its closest relative, Phocaeicola abscessus CCUG 55929T. Reconstruction of phylogenetic and phylogenomic trees revealed that strain 14-104T and P. abscessus CCUG 55929T were clustered as a distinct clade without any other terminal node. The phylogenetic and phylogenomic analyses along with physiological and chemotaxonomic data indicated that strain 14-104T represents a novel species in the genus Phocaeicola, for which the name Phocaeicola oris sp. nov. is proposed. The type strain is 14-104T (=BCRC 81305T= NBRC 115041T).

Malignant transformation of oral potentially malignant disorders in Taiwanese indigenous peoples: A nationwide retrospective cohort study.

Malignant transformation of oral potentially malignant disorders (OPMDs) is a potential cause of oral cancer. Currently, there is no research investigating the rate of malignant transformation of OPMDs into oral cancer in indigenous Taiwanese peoples. This study aimed to retrospectively investigate whether ethnicity (indigenous vs non-indigenous people) plays a role in increasing the malignant transformation rate of OPMDs into oral cancer. This study used data from the oral mucosal screening database and the Cancer Registry File, both of which originated from the National Health Insurance Research Database. We matched the baseline characteristics to control for confounding factors between indigenous peoples and non-indigenous peoples (17,768 indigenous subjects vs 71,072 non-indigenous subjects; 1:4 match) and compared the 2 cohorts. After matching for confounding factors such as age, sex, habits, and OPMD subtype, the malignant transformation rate was not statistically higher for indigenous people than for non-indigenous people. We also discovered that indigenous people with oral verrucous hyperplasia might have a higher chance of malignant transformation into oral cancer than the non-indigenous cohort. We conclude that ethnicity is not a risk factor for the malignant transformation of OPMDs into oral cancer; however, indigenous people with oral verrucous hyperplasia need to pay special attention and are suggested to undergo regular follow-ups for the occurrence of oral cancer.

Development of a salivary autoantibody biomarker panel for diagnosis of oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OSCC) is a destructive disease with increasing incidence. OSCC is usually diagnosed at an advanced stage, which leads to poor outcomes of OSCC patients. Currently, there is a lack of biomarkers with sufficient effectiveness in early diagnosis of OSCC. To ameliorate OSCC screening, we evaluated the performances of salivary autoantibodies (auto-Abs) to nine proteins (ANXA2, CA2, ISG15, KNG1, MMP1, MMP3, PRDX2, SPARC, and HSPA5) as OSCC biomarkers. A multiplexed immunoassay using a fluorescence bead-based suspension array system was established for simultaneous assessment of the salivary levels of the above nine auto-Abs and a known OSCC-associated auto-Ab, anti-p53. Compared to healthy individuals (n = 140), the salivary levels of nine auto-Abs were significantly elevated in OSCC patients (n = 160). Notably, the salivary levels of the 10 auto-Abs in the early-stage OSCC patients (n = 102) were higher than that in the healthy group. Most importantly, utilizing a marker panel consisting of anti-MMP3, anti-PRDX2, anti-SPARC, and anti-HSPA5 for detection of early-stage OSCC achieved a sensitivity of 63.8% with a specificity of 90%. Collectively, herein we established a multiplex auto-Ab platform for OSCC screening, and demonstrated a four-auto-Ab panel which shows clinical applicability for early diagnosis of OSCC.

Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with Candida albicans Infection.

Oral squamous cell carcinoma (OSCC) carcinogenesis involves heterogeneous tumor cells, and the tumor microenvironment (TME) is highly complex with many different cell types. Cancer cell-TME interactions are crucial in OSCC progression. Candida albicans (C. albicans)-frequently pre-sent in the oral potentially malignant disorder (OPMD) lesions and OSCC tissues-promotes malignant transformation. The aim of the study is to verify the mechanisms underlying OSCC car-cinogenesis with C. albicans infection and identify the biomarker for the early detection of OSCC and as the treatment target. The single-cell RNA sequencing analysis (scRNA-seq) was performed to explore the cell subtypes in normal oral mucosa, OPMD, and OSCC tissues. The cell composi-tion changes and oncogenic mechanisms underlying OSCC carcinogenesis with C. albicans infec-tion were investigated. Gene Set Variation Analysis (GSVA) was used to survey the mechanisms underlying OSCC carcinogenesis with and without C. albicans infection. The results revealed spe-cific cell clusters contributing to OSCC carcinogenesis with and without C. albicans infection. The major mechanisms involved in OSCC carcinogenesis without C. albicans infection are the IL2/STAT5, TNFα/NFκB, and TGFß signaling pathways, whereas those involved in OSCC carcinogenesis with C. albicans infection are the KRAS signaling pathway and E2F target down-stream genes. Finally, stratifin (SFN) was validated to be a specific biomarker of OSCC with C. albicans infection. Thus, the detailed mechanism underlying OSCC carcinogenesis with C. albicans infection was determined and identified the treatment biomarker with potential precision medicine applications.

Development of a method for dansylation of metabolites using organic solvent-compatible buffer systems for amine/phenol submetabolome analysis.

Metabolomics, which serves as a readout of biological processes and diseases monitoring, is an informative research area for disease biomarker discovery and systems biology studies. In particular, reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) has become a powerful and popular tool for metabolomics analysis, enabling the detection of most metabolites. Very polar and ionic metabolites, however, are less easily detected because of their poor retention in RP columns. Dansylation of metabolites simplifies the sub-metabolome analysis by reducing its complexity and increasing both hydrophobicity and ionization ability. However, the various metabolite concentrations in clinical samples have a wide dynamic range with highly individual variation in total metabolite amount, such as in saliva. The bicarbonate buffer typically used in dansylation labeling reactions induces solvent stratification, resulting in poor reproducibility, selective sample loss and an increase in false-determined metabolite peaks. In this study, we optimized the dansylation protocol for samples with wide concentration range of metabolites, utilizing diisopropylethylamine (DIPEA) or tri-ethylamine (TEA) in place of bicarbonate buffer, and presented the results of a systemic investigation of the influences of individual processes involved on the overall performance of the protocol. In addition to achieving high reproducibility, substitution of DIPEA or TEA buffer resulted in similar labeling efficiency of most metabolites and more efficient labeling of some metabolites with a higher pKa. With this improvement, compounds that are only present in samples in trace amounts can be detected, and more comprehensive metabolomics profiles can be acquired for biomarker discovery or pathway analysis, making it possible to analyze clinical samples with limited amounts of metabolites.

Taxonomic and Functional Dysregulation in Salivary Microbiomes During Oral Carcinogenesis.

Exploring microbial community compositions in humans with healthy versus diseased states is crucial to understand the microbe-host interplay associated with the disease progression. Although the relationship between oral cancer and microbiome was previously established, it remained controversial, and yet the ecological characteristics and their responses to oral carcinogenesis have not been well studied. Here, using the bacterial 16S rRNA gene amplicon sequencing along with the in silico function analysis by PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2), we systematically characterized the compositions and the ecological drivers of saliva microbiome in the cohorts of orally healthy, non-recurrent oral verrucous hyperplasia (a pre-cancer lesion), and oral verrucous hyperplasia-associated oral cancer at taxonomic and function levels, and compared them with the re-analysis of publicly available datasets. Diversity analyses showed that microbiome dysbiosis in saliva was significantly linked to oral health status. As oral health deteriorated, the number of core species declined, and metabolic pathways predicted by PICRUSt2 were dysregulated. Partitioned beta-diversity revealed an extremely high species turnover but low function turnover. Functional beta-diversity in saliva microbiome shifted from turnover to nestedness during oral carcinogenesis, which was not observed at taxonomic levels. Correspondingly, the quantitative analysis of stochasticity ratios showed that drivers of microbial composition and functional gene content of saliva microbiomes were primarily governed by the stochastic processes, yet the driver of functional gene content shifted toward deterministic processes as oral cancer developed. Re-analysis of publicly accessible datasets supported not only the distinctive family taxa of Veillonellaceae and Actinomycetaceae present in normal cohorts but also that Flavobacteriaceae and Peptostreptococcaceae as well as the dysregulated metabolic pathways of nucleotides, amino acids, fatty acids, and cell structure were related to oral cancer. Using predicted functional profiles to elucidate the correlations to the oral health status shows superior performance than using taxonomic data among different studies. These findings advance our understanding of the oral ecosystem in relation to oral carcinogenesis and provide a new direction to the development of microbiome-based tools to study the interplay of the oral microbiome, metabolites, and host health.

Malignant transformation of oral potentially malignant disorders in Taiwan: An observational nationwide population database study.

ABSTRACT: Oral cancer is one of the leading causes of cancer death, which are mostly preceded by oral potentially malignant disorders (OPMDs). Taiwanese government launched a free oral cancer screening program. The aim of this study was to analyze the malignant transformation rate of OPMDs.This study was based on national-wide oral screening databases. 3,362,232 people were enrolled. Patients clinically diagnosed with leukoplakia, erythroplakia, oral submucosal fibrosis (OSF), oral verrucous hyperplasia (OVH), and oral lichen planus (OLP), from 2010 to 2013, were identified. We followed up OPMD patients in cancer registry databases to analyze the malignant transformation rate.The malignant transformation rates from the highest to the lowest were: OVH > OSF > erythroplakia > OLP > leukoplakia. The malignant transformation rate was 24.55, 12.76, 9.75, 4.23, and 0.60 per 1000 person-years in the OVH, OSF, erythroplakia, leukoplakia, and comparison cohort. The hazard ratio was 8.19 times higher in the OPMD group compared with comparison cohort group, after age and habit adjustment. Female patients with OPMDs had a high risk of malignant transformation.Nationwide screening is very important for early diagnosis. OVH had the highest malignant transformation possibility. Female OPMD patients are a rare but have a relatively high malignant transformation rate.

Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model.

Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg/L) and arecoline (500 mg/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target.

Continuously tunable intensity modulators with large switching contrasts using liquid crystal elastomer films that are deposited with terahertz metamaterials.

A liquid crystal elastomer (LCE) film is successfully deposited with a terahertz metamaterial using thermal evaporation via a programmed electronic shutter and high-efficiency cooling system. The transmittance of the metamaterial at its resonance frequency is monotonically increased from 0.0036 to 1.0 as a pump beam bends the LCE film, so the metamaterial has a large switching contrast of 277 at the frequency. The monotonic increase in the resonance transmittance arises from the constant resonance frequency of the metamaterial at the transmittance modulation and depicts that the metamaterial-deposited LCE film can continuously tune the transmitted intensity of a terahertz beam. The metamaterial-deposited LCE film has potential in developing continuously tunable intensity modulators with large switching contrasts for the application of terahertz imaging and terahertz communication. Therefore, the thermal evaporation expands the application of metamaterials and improves their optical properties.

Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer.

Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.

An immuno-MALDI mass spectrometry assay for the oral cancer biomarker, matrix metalloproteinase-1, in dried saliva spot samples.

Oral cavity cancer is a common cancer type that presents an increasingly serious global problem. Oral squamous cell carcinoma (OSCC) accounts for >90% oral cancer cases. No biomarker tests are currently available for management of this cancer type in clinical practice. Previously, we validated matrix metalloproteinase-1 (MMP1) as one of the most promising salivary biomarkers for OSCC detection. Development of a convenient, rapid and high-throughput assay should further facilitate application of salivary MMP1 measurement for early detection of OSCC. The present study aimed to develop a workflow comprising dry saliva spot (DSS) sampling and immunoenrichment-coupled MALDI-TOF MS (immuno-MALDI) analysis to quantify salivary MMP1. We generated recombinant MMP1 protein and anti-peptide antibodies against MMP1, which were used to optimize the procedures of the entire workflow, including DSS sampling, on-paper protein digestion and elution, KingFisher magnetic particle processor-assisted immuno-enrichment and MALDI-TOF MS analysis. The established workflow was applied to measure salivary MMP1 levels in DSS samples from 5 healthy donors and 9 OSCC cases. The newly developed workflow showed good precision (intra-day and inter-day variations <10%) and accuracy (80-100%) in quantification of MMP1 in DSS samples, with the limit of quantification at 3.07 ng/ml. Using this assay, we successfully detected elevated salivary MMP1 levels (ranging from 5.95 to 242.52 ng/ml) in 7 of 9 OSCC cases while MMP1 was not detectable in samples from the 5 healthy donors. In comparison, the traditional immunoassay was not effective in measuring MMP1 in DSS samples, highlighting the significant advantage of our immuno-MALDI assay. The DSS sampling format confers high flexibility and convenience of collection, storage and delivery of saliva specimens and the KingFisher-assisted immuno-MALDI analysis renders the assay as suitable for high-throughput screening. By combining the two features, the workflow developed in this study should facilitate improvement of molecular diagnostic tests for OSCC using salivary MMP1 as a biomarker.

Malignant development in patients with oral potentially malignant disorders detected through nationwide screening: Outcomes of 5-year follow-up at a single hospital.

BACKGROUND: Although survival rate and quality of life are improved if patients with oral carcinoma can be detected early, however, such lesions are usually asymptomatic; therefore, it is hard to raise awareness. Screening has proved to be cost-effective for early detection. METHODS: Sixty-two patients with oral carcinomas and 555 patients with oral potentially malignant disorders (OPMDs) who were detected through screening were examined the relationship between clinicopathological features and follow-up outcomes. RESULTS: The 5-year cumulative cancer-free interval rate was 94.1%, and the annual malignant transformation rate was 1.16%. The rate of interval carcinoma development from Candida hyperplasia, oral submucous fibrosis, homogeneous leukoplakia, non-homogenous leukoplakia, and verrucous hyperplasia, was 13.6%, 5.7%, 4.6%, 12.1%, and 21.3%, respectively. Significant independent risk factors for interval carcinoma development were heavy betel quid chewing, verrucous hyperplasia, and surgery refusal. CONCLUSIONS: Well-designed risk assessment, treatment, and surveillance program could lead to earlier cancer detection and thereby reduce mortality and morbidity.

Assessment of candidate biomarkers in paired saliva and plasma samples from oral cancer patients by targeted mass spectrometry.

For oral cancer, numerous saliva- and plasma-derived protein biomarker candidates have been discovered and/or verified; however, it is unclear about the behavior of these candidates as saliva or plasma biomarkers. In this study, we developed two targeted assays, MRM and SISCAPA-MRM, to quantify 30 potential biomarkers in both plasma and saliva samples collected from 30 healthy controls and 30 oral cancer patients. Single point measurements were used for target quantification while response curves for assay metric determination. In comparison with MRM assay, SISCAPA-MRM effectively improved (>1.5 fold) the detection sensitivity of 11 and 21 targets in measurement of saliva and plasma samples, respectively. The integrated results revealed that the salivary levels of these 30 selected biomarkers weakly correlated (r < 0.2) to their plasma levels. Five candidate biomarkers (MMP1, PADI1, TNC, CSTA and MMP3) exhibited significant alterations and disease-discriminating powers (AUC = 0.914, 0.827, 0.813, 0.77, and 0.753) in saliva sample; nevertheless, no such targets could be found in plasma samples. Our data support the notion that saliva may be more suitable for the protein biomarker-based detection of oral cancer, and the newly developed SISCAPA-MRM assay could be applied to verify multiple oral cancer biomarker candidates in saliva samples. SIGNIFICANCE: In this work we systematically determined the abundance of 30 selected targets in the paired saliva and plasma samples to evaluate the utility of saliva and plasma samples for protein biomarker-based detection of oral cancer. Our study provides significant evidence to support the use of saliva, but not blood samples, offer more opportunity to achieve the success of protein biomarker discovery for oral cancer detection.

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BACKGROUND: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment. METHODS: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored. RESULTS: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders. CONCLUSION: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.

Effect of arthrocentesis plus platelet-rich plasma and platelet-rich plasma alone in the treatment of temporomandibular joint osteoarthritis: A retrospective matched cohort study (A STROBE-compliant article).

Although the research on using platelet-rich plasma (PRP) for temporomandibular joint osteoarthritis (TMJ-OA) has advanced, no unified standards exist for determining the joint use of arthrocentesis and the injection dose and frequency of PRP. This study aimed to compare the efficacy of 2 TMJ-OA treatment approaches, arthrocentesis plus platelet-rich plasma (A+PRP) and PRP alone, and attempted to provide another potential treatment option with a single injection of 2 mL of high-concentration and high-purity PRP.This retrospective matched cohort study enrolled 208 patients who were treated for temporomandibular disorders (TMDs) in the Department of Oral and Maxillofacial Surgery of Tainan Sin-Lau Hospital between August of 2013 and January of 2016, from which 90 patients were selected for the final analysis. The predictor variables were treatment outcome indicators, including joint crepitus sounds, TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, temporomandibular joint (TMJ) arthralgia, pain when chewing most foods, and maximum assisted opening (MAO). The data were analyzed using χ tests, t tests, and multiple regression analyses.Among the 90 patients, 30 were assigned into the A+PRP group, and 60 were included in the PRP group. A matching method was used to ensure no statistically significant differences in the categorical and continuous variables between the 2 groups. After treatment, both the A+PRP and PRP groups showed improvements in TMJ-OA. The 2 treatment groups did not show statistically significant differences in the symptom improvement rates of joint crepitus sounds, reparative remodeling, and TMJ arthralgia. However, compared with PRP alone, the A+PRP treatment demonstrated superior performance in improving TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, and pain when chewing most foods.Both A+PRP and PRP treatments can effectively improve multiple symptoms of TMJ-OA. Based on the results from this study, we recommend a single injection with 2 mL of high-concentration and high-purity PRP for TMJ-OA treatment. For patients with TMJ-OA accompanied by other clinical symptoms, including TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, and pain when chewing most foods, a treatment approach using arthrocentesis prior to a PRP injection can achieve a higher efficacy.

Risk analysis of malignant potential of oral verrucous hyperplasia: A follow-up study of 269 patients and copy number variation analysis.

BACKGROUND: Oral verrucous hyperplasia is commonly observed in the oral cavity of betel quid chewers and is a potential malignant disorder. However, the prognostic factors and genetic alterations of oral verrucous hyperplasia are unclear. METHODS: We calculate the survival rate and prognostic factors using a Kaplan-Meier analysis and Cox proportional hazards regression model. Copy number variations were analyzed using a single-nucleotide polymorphism (SNP) array. RESULTS: The 5-year disease-free and cancer-free survival rates of patients with oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions were risk factors for malignant transformation, whereas dysplasia did not affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 were associated with the poor prognosis of oral verrucous hyperplasia. CONCLUSION: Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions are high-risk factors of patients with oral verrucous hyperplasia. The 5-copy number variation-associated genes could be used for early diagnosis and predicting the prognosis.