Mass cytometry and transcriptomic profiling reveal PD1 blockade induced alterations in oral carcinogenesis.

Oral squamous cell carcinoma is the predominant subtype of head and neck squamous cell carcinoma, characterized by a challenging prognosis. In this study, we established a murine model of oral carcinogenesis using 4-nitroquinoline-1-oxide (4-NQO) induction to investigate the impact of immunotherapy on microenvironmental alterations. Mice in the precancerous condition were randomly divided into two groups: one receiving programmed death-1 (PD1) monoclonal antibody treatment and the other, control immunoglobulin G. Our observations showed that while PD1 blockade effectively delayed the progression of carcinogenesis, it did not completely impede or reverse it. To unravel the underlying reasons for the limited effectiveness of PD1 blockade, we collected tongue lesions and applied mass cytometry (CyTOF) and RNA sequencing (RNA-seq) to characterize the microenvironment. CyTOF analysis revealed an increased macrophage subset (expressing high levels of IFNγ and iNOS) alongside a diminished Th1-like subset (exhibiting low expression of TCF7) and three myeloid-derived suppressor cell subsets (displaying low expression of MHC Class II or IFNγ) following anti-PD1 treatment. Notably, we observed an increased presence of cancer-associated fibroblasts (CAFs) expressing collagen-related genes after PD1 blockade. Furthermore, we found a negative correlation between the infiltration levels of CAFs and CD8+ T cells. These findings were validated in murine tongue tissue slides, and publicly available multi-omics datasets. Our results suggest that CAFs may impair the therapeutic efficacy of PD1 blockade in oral carcinogenesis by the remodeling of the extracellular matrix.

Angelicin inhibits cell growth and promotes apoptosis in oral squamous cell carcinoma by negatively regulating DUSP6/cMYC signaling pathway.

Angelicin has been reported to have antitumor effects on many types of cancer. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. We performed cell cycle and apoptosis analyses to assess the effect of angelicin on OSCC cells. We conducted RNA-seq studies to reveal differentially expressed genes (DEGs). Dual-specificity phosphatase 6 (DUSP6) and c-MYC were strongly down-regulated differential genes. Silencing RNA (siRNA) was used to knockdown DUSP6. The mouse xenograft model was used to mimic OSCC. Angelicin inhibited OSCC in vitro. We found that DUSP6 interacted with c-MYC. DUSP6 knockdown group and DUSP6 knockdown + angelicin group had similar effects of OSCC cells. Angelicin could reduce tumor formation, DUSP6, and c-MYC expression in vivo. Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.

Pemphigus oral lesions area index (POLAI): A new scoring scale for assessing oral pemphigus vulgaris.

OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.

Oral epithelial dysplasia detection and grading in oral leukoplakia using deep learning.

BACKGROUND: The grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia. METHODS: Four convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model. RESULTS: EfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4-90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4-90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843). CONCLUSIONS: E-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice.

circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling.

OBJECTIVES: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. MATERIALS AND METHODS: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. RESULTS: Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. CONCLUSION: The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients.

MRTF-A/SRF signaling suppresses invasion of oral squamous cell carcinoma.

BACKGROUND: Serum response factor (SRF) and myocardial-associated transcription factor-A (MRTF-A) had different regulatory effects on the tumorigenesis and development in different cancers. However, the role of MRTF-A/SRF in oral squamous cell carcinoma (OSCC) remains to be determined. METHODS: CCK-8 assay, cell scratch experiment, and transwell invasion assay were conducted to investigate the effects of MRTF-A/SRF on biological behavior of OSCC cells. The expression pattern and prognostic value of MRTF-A/SRF in OSCC were analyzed based on cBioPortal website and TCGA database. Protein-protein interaction network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to investigate related pathways. The effect of MRTF-A/SRF on epithelial-mesenchymal transformation (EMT) of OSCC cells was explored by western blot assay. RESULTS: Overexpression of MRTF-A/SRF inhibited the proliferation, migration, and invasion of OSCC cells in vitro. High expression of SRF was related to better prognosis of OSCC patients on hard palate, alveolar ridge, and oral tongue. Besides, overexpression of MRTF-A/SRF inhibited the EMT of OSCC cells. CONCLUSION: SRF was closely related to the prognosis of OSCC. High expression of SRF and its co-activator MRTF-A inhibited proliferation, migration, and invasion of OSCC cells in vitro, possibly via EMT suppression.

Hydroxychloroquine is effective in oral lichen planus: A multicenter, randomized, controlled trial.

OBJECTIVES: This study was aimed to evaluate the safety and benefit of short-term application of hydroxychloroquine in the management of atrophic/erosive/ulcerative oral lichen planus (OLP). METHODS: This multicenter, randomized, controlled, evaluator-blinded, prospective clinical trial was performed from October 1, 2019, to September 1, 2022. A total of 99 patients were randomized to receive systemic use of hydroxychloroquine (n = 50), or topical use of 0.05% dexamethasone (n = 49) for 4 weeks. The response to both treatment modalities was evaluated according to reticulation, hyperemic, and ulceration (RHU) score and visual analog scale (VAS) score. RESULTS: After 4 weeks of medication, both groups showed substantial reduction in RHU and VAS score (p < 0.05). In hydroxychloroquine group, the average of RHU score was reduced from 10.60 to 7.68 (dropped 27.49%), and the average of VAS score was reduced from 3.74 to 2.47 (dropped 34.09%). There were no differences between the two groups in reduction of RHU score and VAS score (p > 0.05). Single factor analysis found hyperemic area (p = 0.019) and erosive/ulcerative area (p = 0.024) had impacts on drug efficacy of hydroxychloroquine, and logistic regression revealed that no factors (p > 0.05) influenced its efficacy. CONCLUSION: These findings indicate hydroxychloroquine is a safe and effective agent in treating atrophic/erosive/ulcerative OLP.

A multi-center cross-sectional study of 1495 Chinese oral lichen planus patients.

OBJECTIVE: To explore the clinical epidemiological characteristics of oral lichen planus (OLP) and risk factors for erosive/ulcerative OLP. MATERIALS AND METHODS: Patients diagnosed with OLP from 11 different hospitals were included in the study. Descriptive statistical methods were used to explore the clinical epidemiological characteristics and logistic regression, sensitivity analysis, and subgroup analysis were utilized to explore the risk factors for erosive/ulcerative OLP. RESULTS: The average age of patients was 49.2 ± 13.3 years, and 61.4% of the patients were women. The ratios of patients with reticular, hyperemic/erythematous, and erosive/ulcerative lesions were 47.9%, 27.8%, and 24.2%, respectively. Analysis of risk factors for erosive/ulcerative OLP identified the following variables: age, course of disease of 12 months or more, II°-III° dental calculus, hypertension, diabetes, and heart disease, as well as regions of habitation. Subgroup analysis showed significant differences in risk factors for erosive/ulcerative OLP in patients with and without risk behaviors. CONCLUSION: The clinical epidemiological characteristics of patients with OLP in the Chinese population in this study are basically consistent with existing reports in developed countries. And we identified clinical characteristics associated with erosive/ulcerative OLP through clinical epidemiological analysis.

First Report of Fusarium solani associated with Twig Canker of English Walnut (Juglans regia L.) in Xinjiang, China.

English walnut (Juglans regia L.) is a perennial deciduous fruit tree, and an economically important hardwood tree species cultivated worldwide. As one of the important economic crops, English walnut is also widely cultivated in Xinjiang. In September 2019, twig canker symptoms were observed on English walnut in several orchards, with approximately 15% to 40% disease incidence in southern Xinjiang region (79º95'E, 40º37'N). The branch lesions were long oval, concave, and black to brown. Leaves of the affected branches turned yellow and the branches eventually died. Infected twigs were collected from an infected tree in an orchard. Symptomatic tissue from the margins of cankers was surface disinfested with 75% ethanol for 60 s, rinsed 3 times with sterile water, and then incubated on potato dextrose agar medium (PDA) at 25 ℃ under a 12-hr photoperiod in Light incubator for 7 days. Seven fungal isolates showing similar morphology were obtained from the symptomatic tissue. All the fungal cultures had a pink-white color with loose, cottony mycelium, and the underside of the colonies were light brown. Macroconidia were slightly curved, with one to six septa, both ends were slightly sharp, and they measured 22.8 to 38.5 × 3.5 to 6.7 µm (27.4 ± 0.6 × 4.2 ± 0.3 µm, n=50). Microconidia were oval, hyaline, zero to one septa, measuring 4.5 to 9.6 × 1.8 to 2.3 µm (6.8 ± 0.3 × 2.1 ± 0.1 µm, n=50). According to the morphological characteristics, the seven isolates were identified as a member of the Fusarium solani species complex (Summerell et al. 2003). Genomic DNA was extracted from the representative isolate HSANTUAN2019-1, and the internal transcribed spacer (ITS) region, the translation elongation factor 1-alpha (TEF) were amplified with the primer pairs ITS1/ITS4 (White et al. 1990) and EF1-F/EF2-R (O' Donnell et al. 2010), respectively. The sequences submitted to GenBank (accession nos. OP271472 for ITS, OP293104 for TEF) showed high similarity with the reference sequences of F. solani (ITS, OL691083 [100%]; TEF, HE647960 [99.86%]). Pathogenicity of the seven isolates were assessed on 1-year-old branches of English walnut in the field. Healthy branches (40) were wounded with a sterilized hole punch, and then inoculated with isodiametric mycelial PDA plugs (5 branches per fungal isolate). Five branches were inoculated with sterile PDA plugs as a negative control. The inoculations were performed three times. All treatments were wrapped with fresh film for 3 days. Dark brown necrotic lesions were observed on all inoculated branches 22 days post-inoculation. The controls had no symptoms. The pathogen was reisolated from all the inoculated branches, fulfilling Koch's postulates. To our knowledge, this is the first report of F. solani causing twig canker on English walnut in Xinjiang, China. Twig canker disease often cause a large number of branches to dry out and die. If the disease control and prevention is neglected, the productivity of the English walnut will be seriously affected in the cultivation area. Our finding will provide valuable information for prevention and management of twig canker on English walnut.

Association between human herpes simplex virus and periodontitis: results from the continuous National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. METHODS: The National Health and Nutrition Examination Survey (NHANES) data for 2009-2010, 2011-2012 and 2013-2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. RESULTS: There were 4,733 participants aged 30-50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P < 0.001) and HSV-2 (OR = 1.06, P = 0.030) infection was significantly associated with periodontitis. In subgroup analyses, compared with patients without HSV infection, patients with HSV-1( +) & HSV-2( +) and HSV-1( +) & HSV-2(-) infection showed higher risk of periodontitis in all subgroups (OR = 1.15, OR = 1.09, P < 0.001), while patients with HSV-1(-) & HSV-2( +) infection showed higher risk of and periodontitis only in the subgroup of people aged 40-50 years (OR = 1.10, P = 0.032) and the Mexican-American subgroup (OR = 1.35, P = 0.042). When only severe periodontitis is considered, HSV infection was associated with periodontitis, no matter the patient was infected with either of the virus or both. CONCLUSIONS: HSV-1 infection was significantly associated with periodontitis and severe periodontitis, while HSV-2 infection was associated with severe periodontitis, and periodontitis in 40-50-year-olds and Mexican-Americans.

Single-cell transcriptomics dissects premalignant progression in proliferative verrucous leukoplakia.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL. METHODS: We performed single-cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression. RESULTS: By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation. CONCLUSION: Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes.

Incidence and Survival of Oral Cavity and Oropharyngeal Cancer in the United States From 1975 to 2018.

PURPOSE: Oral cavity and oropharyngeal cancer (OC-OPC) is one of the most common cancers in the world. A comprehensive investigation of the temporal changes in incidence, overall survival (OS), and associated factors of this disease may facilitate the formulation and modification of public health control measures. METHODS: This is a retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database (1975 to 2018). Average annual percentage change (APC) in incidence was calculated by linear regression. Associations of incidence and OS with time and covariates (age, race, gender, site, grade, income, and residence) were analyzed. The Kaplan-Meier log-rank test was used for analysis of OS. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by Cox regression models. RESULTS: This study included 92,685 patients diagnosed with OC-OPC in Surveillance, Epidemiology, and End Results 9 database. An overall decrease was discovered in the incidence, especially among the Black population (APC, -15.2; 95% CI, -17.5 to -13.0; P < .01), and among those at 60+ years of age (APC, -12.8; 95% CI, -18.6 to -7.0; P < .01). Notably, the incidence among the rural population (APC, 7.1; 95% CI, 4.4 to 9.8; P < .01) increased. Residence and gender had the greatest effect on changes in incidence. Univariate analysis showed that the prognosis was worse in patients diagnosed between 1975 and 2000, patients from the Black population (HR, 1.87; 95% CI, 1.81 to 1.93; P < .01), patients at 60+ years of age (HR, 1.64; 95% CI, 1.61 to 1.68; P < .01), and patients with OPC. Interestingly, multivariate analysis showed no significant difference between OPC and OC, and the results of other subgroups were similar to univariate analysis. CONCLUSION: The results of this study indicate that more attention should be paid to facilitating OC-OPC prevention in rural population, as well as improving management of this disease in Black and elderly populations, and among patients with higher grade of disease and lower income.

PD-1 blockade prevents the progression of oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck with a poor prognosis. Oral cancer development is a multistep process involving carcinogenesis. Though significant advances in cancer immunotherapy over the years, there is lack of evidence for T-cell exhaustion during oral carcinogenesis. Clinical specimens from healthy donors and patients diagnosed with oral leukoplakia (OLK) or OSCC were collected for immunohistochemical staining with PD-L1, CD86, CD8, PD-1 and CTLA-4 antibodies. Meanwhile, chemically induced mouse models of oral carcinogenesis were constructed with 4-nitroquinolone-N-oxide induction. Exhaustion status of T cells was measured by flow cytometry for spleens and by multiplex immunohistochemistry for formalin-fixed paraffin-embedded lesions in multiple stages of oral carcinogenesis. The efficacy of PD-1 blockade with or without cisplatin treatment was evaluated on the mice in precancerous and OSCC stages. We observed higher expression of PD-1 in the human OLK and OSCC tissues compared with the normal, while low expression CTLA-4 in all oral mucosa tissues. Animal experiments showed that the exhausted CD4+ T cells existed much earlier than exhausted CD8+ T cells, and an increased ratio of stem-like exhausted T cells and partially exhausted T cells were detected in the experimental groups. Besides, the expression of immune checkpoint markers (PDCD1, CTLA4 and HAVCR2) was strongly positively correlated with cytokines (IFNG and IL-2). In summary, T-cell exhaustion plays a vital role in oral carcinogenesis, and PD-1 blockade can prevent the progression of oral carcinogenesis.

Application of medical magnifying loupes in diagnosis of oral mucosal diseases.

: To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.

Management of burning mouth Syndrome: A position paper of the Chinese Society of Oral Medicine.

BACKGROUND: Burning mouth syndrome is a syndrome with tongue as the main affected site and burning pain as the main complaint. Although a variety of therapies have been reported to treat BMS, there is a lack of widely recognized therapies and it is still a dilemma for clinicians to treat BMS. OBJECTIVE: To develop the position paper and provide the references for clinical practice of BMS in China. METHODS: Under the guidance of WHO (World Health Organization) Handbook for Guideline Development, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach as a tool to develop this position paper in the following steps: setting up the groups, formulating the clinical questions and choosing the outcomes, retrieving and synthesizing of evidence, assessing the evidence, investigating the patients' values and preferences, developing the recommendations, reviewing the recommendations, and writing the position paper. RESULTS: The 27 recommendations were formed from the following 7 aspects: pre-treatment examination, removal of stimuli, medication, physical therapy, psychological therapy, and antipsychotics. There are 3 strong recommendations and 12 weak recommendations in pre-treatment examination and removal of stimuli, as well as 12 weak recommendations in therapies. CONCLUSION: The Chinese position paper for management of BMS has been developed, which could provide the references for clinical practice of BMS in China. Twenty-seven recommendations were formed based on consensus of experts on the balance of benefits vs side effects, evidence, cost, and patients' values and preferences, although the quality of evidence is relatively low.

Histone modifications in oral squamous cell carcinoma and oral potentially malignant disorders.

Oral squamous cell carcinoma (OSCC) is a common malignancy with dismal prognosis without effective therapeutic options in advanced cases. The evolution from oral potentially malignant disorders to OSCC has poorly described underlying epigenetic features. With the ability of silencing or activation of vital genes, histone modifications' and modifiers' potentiality for early diagnosis, prognosis predicting, and therapy in OSCC were evaluated by extensive epigenetic studies. This review investigates the roles of dysregulated histone modifications and the associated modifying enzymes in OSCC onset and progression. Also, we focus on the current advances of histone modifications as therapeutic targets and the potential value of epi-drugs.

Efficacy evaluation of photodynamic therapy for oral lichen planus: a systematic review and meta-analysis.

BACKGROUND: Photodynamic therapy (PDT) is a new option for oral lichen planus (OLP) management; however, there are different opinions on the efficacy of PDT for OLP. The aim of this study was to comprehensively assess the efficacy of PDT in the treatment of OLP and compare PDT with steroid therapy. METHODS: A systematic review and meta-analysis were conducted to assess the curative effect of PDT. Five electronic databases were searched, PubMed, Web of Science, the Cochrane Library, Embase, and EBSCO up to 1 December, 2019. Random and fixed effects models for pooled estimates calculation were used and the Meta package of R was applied. RESULTS: Pooled estimates revealed that, after PDT, the lesion size decreased by 1.53 cm2 (95% confidence interval (CI): 0.71-2.35) after PDT and the partial response (PR) was 0.77 (95% CI: 0.65-0.85). The visual analogue scale (VAS) score decreased by 3.82 (95% CI: 2.80-4.85) and the Thongprasom sign score decreased by 1.33 (95% CI: 0.56-2.10) after PDT. Subgroup analyses revealed that the 5-aminolevulinic acid (5-ALA) was more effective than methylene blue (MB), with a PR of 0.87 (95% CI: 0.80-0.91). The topical use of 5-ALA yielded a better response than gargling methylene blue. In terms of VAS, the diode laser showed a better clinical PR in the treatment of OLP. In terms of changes in lesion size, the efficacy of the semiconductor laser was higher than that of the diode laser. PDT had a similar efficacy to topical corticosteroids, as shown by pooled estimates of five randomised controlled trials with 139 lesions. CONCLUSION: This systematic review indicates that PDT is an effective treatment modality for the management of OLP. PDT is as effective as topical corticosteroid in the treatment of OLP and could be used for cases resistant to steroids or when steroids are contraindicated.

In situ measurement of miR-138 expression in oral squamous cell carcinoma tissue supports the role of this microRNA as a tumor suppressor.

BACKGROUND: Oral squamous cell carcinoma is the eighth most common cancer worldwide with a relatively high rate of metastasis (~40%). Previously, we showed that microRNA-138 serves as a functional tumor suppressor and plays an important role in oral squamous cell carcinoma metastasis. However, to date, microRNA-138 expression has not been examined in this tumor tissue. Herein, we demonstrated that microRNA-138 expression is downregulated in metastatic oral squamous cell carcinoma specimens using tissue microarray technology with in situ hybridization. METHODS: The study included 254 oral squamous cell carcinoma patients from two centers (160 from the Chengdu center and 90 from the Guangzhou center) and four healthy volunteers. RESULTS: Multivariate analysis showed that microRNA-138 expression was independent of tumor stage, age, gender, smoking, and alcohol consumption in oral squamous cell carcinoma patients. Interestingly, patients that expressed lower levels of microRNA-138 (determined by in situ hybridization) were more prone to regional lymph node metastasis and exhibited poorer outcomes. These findings support the role of microRNA-138 as a tumor suppressor in oral squamous cell carcinoma. CONCLUSION: In summary, the expression level of microRNA-138 is negatively correlated with oral squamous cell carcinoma metastasis; the lower the expression of microRNA-138, the higher the rate of metastasis and the poorer the prognosis of the patients. Therefore, our study confirms that microRNA-138 serves as a tumor suppressor and plays a functional role in oral squamous cell carcinoma tumor metastasis; microRNA-138 constitutes a promising prognosis biomarker and therapeutic target for oral squamous cell carcinoma with metastasis potential.

Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis.

A series of studies are dedicated to research the clinical outcomes of oral leukoplakia (OLK) treated with carbon dioxide laser (CO2 laser); however, the results vary from studies especially related to recurrence and malignant transformation. Hence, we performed this meta-analysis to precisely evaluate the malignant transformation of OLK dealt with CO2 laser and investigate the association between its malignant transformation and kinds of related risk factors, such as gender, clinical classification, long duration of leukoplakia, and degree of epithelial dysplasia and lesion regions. We performed a systematic search of the Cochrane Library, EMBASE, Pubmed, Web of Science, and SCOPUS. Single-arm rate of the overall risk of malignant transformation in OLK treated with CO2 laser was calculated using the Der-Simonian Liard method. We applied subgroup analysis to compare the risk of malignant transformation according to the degree of epithelial dysplasia, clinical type, and region of OLK. Moreover, a pooled odds ratio (OR) is calculated, along with its 95% confidence interval (CI), to compare the risk of malignant transformation according to patients' gender, tobacco, and alcohol consumption. We used the meta package of R software for quantitative data synthesis and analysis. The rate of malignant transformation of OLK treated with carbon dioxide laser ranged from 0 to 15.38% in included studies. The overall rate of malignant transformation of OLK treated with CO2 laser is 4.50% under the random effect model [95% CI 0.0305-0.0659]. A systematic review of observational studies of OLK reported that the estimated overall (mean) malignant transformation rate was 3.5%, with a wide range between 0.13 and 34.0%. Interestingly, our result revealed that it was the male, homogeneous type, no tobacco consumption, and without alcohol-use who had a higher tendency of malignancy after laser surgery. However, this result lack statistically significant data. Generally speaking, whether oral leukoplakia patients underwent laser surgical treatment or not, it may have little effect on malignant transformation. In addition, we strongly advise that it had better not to perform CO2 laser intervention on OLK patients with the following clinical characteristics: homogeneous type, male, no tobacco consumption, and without alcohol-use. Evidence is still lacking in terms of relationship between malignant transformation and risk factors among OLK patients managed with CO2 laser. Thus, these associations should be further investigated.

Long non-coding RNA implicated in the invasion and metastasis of head and neck cancer: possible function and mechanisms.

Head and neck cancer (HNC) ranks as the 6th most common malignancy across the world. Metastasis is a hallmark of cancer, primarily contributing to the relapse and poor prognosis of HNC. Recently, long noncoding RNAs (lncRNAs), previously considered as non-functional, are increasingly appreciated by scholars to play crucial roles in mediating HNC metastasis. LncRNAs, which are located in the nucleus and cytoplasm, mainly exert their function via epigenetic modification, transcriptional control and translational regulation. As several lncRNAs are presently demonstrated to participate in HNC metastasis, we make a summary of the functions and mechanisms regarding these lncRNAs. As shown in the literature, most lncRNAs appear to promote the metastasis of HNC. Hence, we primarily discuss the lncRNAs involved in enhancing metastasis. Additionally, more studies are needed to understand those lncRNAs without clear mechanisms. Furthermore, we introduced the upstream regulator for the aberrant expression of lncRNAs in HNC. Finally, we concisely addressed future research prospects of lncRNAs, particularly the interplay between lncRNAs and tumor immunity as well as lncRNA-targeted therapeutic techniques, and we introduced clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possibly transformative tool to study lncRNAs. Although lncRNA research is still in the initial stage, it holds great promise to be applied as a prognosticator of HNC and a therapeutic target to inhibit HNC metastasis, which could significantly enhance the outcome of HNC patients.