Deep learning-enabled fluorescence imaging for surgical guidance: in silico training for oral cancer depth quantification.

Significance: Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. Aim: A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. Approach: A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. Results: The performance of the CSH model was superior when presented with patient-derived tumors ( P -value < 0.05 ). The CSH model could predict depth and concentration within 0.4 mm and 0.4 µ g / mL , respectively, for in silico tumors with depths less than 10 mm. Conclusions: A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.

Risk stratification scheme based on the TNM staging system for dogs with oral malignant melanoma centered on clinicopathologic presentation.

Introduction: Oral malignant melanoma (OMM) is the most common malignant oral neoplasm in dogs. Tumor recurrence, progression, and regional and distant metastasis remain major obstacles despite advanced therapy. Tumor size has been a consistent, key independent prognostic factor; however, other clinical and histopathologic features impact prognosis and likely influence optimal treatment strategies. Adoption of a risk stratification scheme for canine OMM that stratifies groups of dogs on defined clinicopathologic features may improve reproducible and comparable studies by improving homogeneity within groups of dogs. Moreover, it would aid in the generation of multidisciplinary prospective studies that seek to define optimal treatment paradigms based on defined clinicopathologic features. Methods: To build a platform upon which to develop a risk stratification scheme, we performed a systematic review of clinicopathologic features of OMM, with particular attention to levels of evidence of published research and the quantitative prognostic effect of clinicopathologic features. Results: Tumor size and presence of bone lysis were repeatable features with the highest level of evidence for prognostic effects on survival. Overall, with strict inclusion criteria for paper review, the levels of evidence in support of other, previously proposed risk factors were low. Factors contributing to the challenge of defining clear prognostic features including inconsistencies in staging and reporting of prognostic variables, incomplete clinical outcome data, inhomogeneous treatment, and absence of randomized controlled studies. Discussion: To overcome this in the future, we propose a risk stratification scheme that expands the TNM system to incorporate specific designations that highlight possible prognostic variables. The ability to capture key data simply from an expanded TNM description will aid in future efforts to form strong conclusions regarding prognostic variables and their influence (or lack thereof) on therapeutic decision-making and outcomes.

Non­obstructive mesenteric ischaemia during drug therapy for maxillary cancer: A case report.

Non-occlusive mesenteric ischaemia (NOMI) refers to irreversible intestinal ischaemia and necrosis in the absence of organic obstruction to the mesenteric blood vessels. In cases of delayed diagnosis, the prognosis is poor and the mortality rate is 58-70%, being the highest among patients with acute mesenteric ischaemia. The risk factors for this disease include heart disease, sepsis, and administration of catecholamines and digitalis; however, there are few reports of its onset during drug therapy for malignant tumours. The present study reported the case of an 85-year-old man who developed NOMI during drug therapy for maxillary cancer. The patient was diagnosed with right maxillary carcinoma, for which paclitaxel, carboplatin and cetuximab (PCE) therapy was administered. Four days after starting the second course of PCE therapy, the patient visited the emergency department of our hospital with chief complaints of melena and abdominal pain. Contrast-enhanced computed tomography revealed ischaemia from the transverse to the descending colon, leading to a diagnosis of NOMI. Colectomy and colostomy were performed during the emergency surgery on the same day. Although the patient's general condition improved, he was transferred to a recuperation facility for palliative care.

Treatment strategies for patients over 80 years of age with oral squamous cell carcinoma.

OBJECTIVE: To analyze the clinical characteristics of patients with oral squamous cell carcinoma aged ≥80 years, focusing on surgical treatments. STUDY DESIGN: We reviewed patients with oral squamous cell carcinoma aged ≥80 years who underwent surgery between 2005 and 2018. Basic information, comorbidities, multiple primary cancers, initial treatment, complications, and outcomes were evaluated. RESULTS: Of 197 patients aged ≥80 years, 119 patients underwent surgery (50 males, 69 females; mean age: 83.5 years). The gingiva was the most common primary tumor site (63 patients, 52.9 %). The stage classification was stage I in 35 patients (29.4 %), stage II in 44 (37 %), stage III in 16 (13.4 %), stage IVA in 22 (18.5 %), and stage IVB in 2 (1.7 %). Comorbidities were identified in 112 patients (94.1 %). Surgery was the initial treatment in 111 patients (93.3 %). Eight (6.7 %) patients received postoperative adjuvant chemotherapy/radiotherapy; 20 patients (16.8 %) underwent free tissue transplantation. Perioperative complications were observed in 36 patients (30.3 %). The cumulative 5-year and 10-year overall survival rates were 82 % and 68.3 %, respectively; the disease-specific survival rates were 90 %. CONCLUSION: Good treatment outcomes were obtained with radical surgery. Surgery should be the first choice if quality of life is assured and there are no issues with surgical tolerance, regardless of age.

Burden of oral cancer and associated risk factors at national and state levels: A systematic analysis from the global burden of disease in India, 1990-2021.

BACKGROUND: Oral cancer is the sixth most prevalent cancer globally, posing a significant health concern, especially in India, where it accounts for one-third of the global cases. Despite high incidence and mortality rates, comprehensive national and regional data on risk factors and trends are scarce. METHODS: This study analyzed data from the Global Burden of Disease (GBD) 2021 report, focusing on the age-standardized incidence rate (ASIR), mortality rate (ASMR), disability-adjusted life years (ASDR), and prevalence rate (ASPR) of oral cancer in India from 1990 to 2021. Joinpoint regression analysis was used to assess trends, and ARIMA models were applied to forecast future trends from 2022 to 2031. RESULTS: From 1990 to 2021, India experienced a moderate increase in oral cancer mortality, with ASMR rising from 5.32 to 5.92, reflecting an annual percentage change (APC) of 11.18 %. ASDR increased from 152.94 to 163.61 (APC of 6.98 %), and ASPR showed a marked rise from 15.71 to 25.46 (APC of 62.06 %). The burden varied significantly across states. Gender disparities were observed, with males consistently exhibiting higher incidence and mortality rates. ARIMA forecasts projected an upward trend in oral cancer metrics from 2022 to 2031, with ASIR expected to reach 10.15 per 100,000 and ASPR 29.38 per 100,000 by 2031. CONCLUSIONS: The study reveals a persistent and growing burden of oral cancer in India, highlighting the influence of lifestyle and socioeconomic factors. Targeted strategies to mitigate risk behaviors, improve early detection, and address disparities are urgently needed to reduce the disease's impact.

[The Oral Microbiome in the Development of Oral Cancer].

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.

The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma.

BACKGROUND: Long non-coding RNA LINC00319 has been implicated in the progression of various cancers, including oral squamous cell carcinoma (OSCC). While our previous work has revealed some aspects of LINC00319's role in OSCC, including its upregulation and involvement in a competing endogenous RNA (ceRNA) mechanism, the full extent of its functions and regulatory mechanisms in OSCC progression remain to be fully elucidated. OBJECTIVE: This study aimed to investigate the function of LINC00319 in OSCC and its potential interaction with the STAT3 signaling pathway, thus uncovering novel regulatory mechanisms and therapeutic targets. METHODS: Bioinformatics analysis was performed using TCGA data to evaluate LINC00319 expression in OSCC tissues and its correlation with STAT3 signaling. The direct binding between LINC00319 and STAT3 was examined by RNA pull-down, FISH, and RIP assays. Functional experiments, including CCK-8, transwell migration and invasion assays, and western blot analysis of EMT markers and STAT3 pathway activation, were conducted to assess the effects of LINC00319 on OSCC cell behaviors and its interaction with the STAT3 signaling pathway. In vivo xenograft models were established to validate the role of LINC00319 in tumor growth and STAT3 activation. RESULTS: LINC00319 expression was significantly upregulated in OSCC tissues compared to normal tissues, and high LINC00319 expression correlated with STAT3 signaling activation. Mechanistically, LINC00319 directly bound to STAT3 protein and promoted its phosphorylation at Tyr705. LINC00319 overexpression enhanced, while its knockdown suppressed, the proliferation, migration, invasion, and EMT of OSCC cells. These oncogenic effects were mediated through STAT3 activation and could be reversed by the STAT3 inhibitor stattic. In vivo experiments further confirmed that LINC00319 silencing inhibited tumor growth and STAT3 phosphorylation. CONCLUSION: This study uncovers that LINC00319 promotes OSCC tumorigenesis by directly binding to and activating STAT3 signaling. These findings provide new insights into the regulatory mechanisms of STAT3 by long non-coding RNAs and highlight the potential of LINC00319 as a biomarker and therapeutic target in OSCC.

Comparative analysis of PDL1 and cluster of differentiation 68 marker expression in oral squamous cell carcinoma patients: Correlation with depth of invasion and immunofluorescence through immunohistochemistry.

Background: Over the past 5 years, the use of immune checkpoint inhibitors in the treatment of head-and-neck squamous cell carcinoma (HNSCC) has increased. Both programmed death-ligand 1 (PD-L1) and cluster of differentiation 68 (CD68) are overexpressed in various carcinomas. Consequently, evaluating the expression of CD68 and PD-L1 in HNSCC lesions may lead to detecting a possible marker for HNSCC. This study aimed to evaluate the expression of PDL1 and CD68 markers in a patient with oral squamous cell carcinoma (OSCC) and examine its relationship with depth of invasion (DOI) and immunofluorescence (IF) through immunohistochemistry. Materials and Methods: This cross-sectional study was conducted in the School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, Department of Oral and Maxillofacial Pathology. Thirty-four paraffin blocks and demographic information of 15 female and 19 male OSCC patients were collected. Following sample preparations, immunohistochemical staining was performed. Subsequently, each tissue section was analyzed for tumor-infiltrating lymphocytes by CD68 marker and PD-L1 expression. Data analysis was conducted using SPSS software (version 25). Chi-square, Shapiro-Wilk, and independent t-analytical tests were employed for statistical assessments. P < 0.05 was remarked as statistically significant. Results: CD68 and PDL1 expression in the squamous cell carcinoma (SCC) group was higher than the control group (P < 0.001). There was an increasing expression of PDL1 and CD68 as the grade of the disease progressed (P < 0.001 for each), as well as an increasing expression of IF and DOI. Conclusion: The expression levels of CD68 and PDL1 were elevated in SCC tissues in comparison to the unaffected, healthy parts of the tissue section.

Clinicopathological Characteristics, Prognostic Factors, and Treatment Outcomes of Patients with Oral Tongue Squamous Cell Carcinoma Treated with Glossectomy: A Tertiary Oncology Center Experience.

Oral tongue squamous cell cancer (OTSCC) is one of the most prevalent cancers worldwide and incidence increases with age. An alarming increase in the incidence of OTSCC in the younger age group. This study aimed to explore clinical and histopathological characteristics, survival, and other post-surgical outcomes in patients with OTSCC treated with glossectomy through the Department of Otolaryngology-Head & Neck Surgery at the Ministry of National Guard Health Affairs (MNGHA) within our study period. This is a retrospective study carried out through the collection and analysis of data from medical charts of 56 patients with oral tongue cancer who were treated by glossectomy. Treatment was initiated from January 2010 to December 2021. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were collected and analyzed. At diagnosis, 62.5% were tobacco smokers, 46.8% had poor dental hygiene, and 76.8% had ulcerative lesions. Furthermore, 33 cases presented with early-stage clinical disease and 23 cases with advanced stage. The median follow-up was 54 months, 28 patients (50%) were free for 3-5 years. Patients who were free on 5-year follow-up had a significantly higher percentage of negative lymphovascular and perineural invasion (p < 0.05). Additionally, 12 patients (21.4%) had developed recurrence. Mortality in all cases was 30.3, but mortality-related cancer was 19.6%. Locoregional failure remains the main cause of treatment failure in resectable OTSCC. Pathological T-stage, N-stage, LVI, PNI, ECE, and LNR are all considered strong prognostic factors.

Versatility of Islanded Nasolabial Flap Based on Facial Artery and Vein for Reconstruction of Oral Cancer Defects, Experience in a Tertiary Care Center.

Introduction: Conventional nasolabial flap has been widely used for reconstruction for head and neck defects. Recent decades witnessed modification of this flap like islanded version based on subcutaneous pedicle or facial artery and vein. The later modification obviated a need for pedicle division, secondary procedures and facilitates reach of the flap to distant sites. Especially, the islanded nasolabial flap pedicled on facial artery and vein can have a long pedicle to conveniently reach the tongue, floor of mouth when the flap is routed through retromandibular area. Methods: A retrospective analysis was done on 14 patients analyzing the functional outcome like deglutition, speech, and aesthetic outcome of flap donor area, recruiting patients in which islanded nasolabial flap was done based on facial vessels for early stages of cancer tongue and lip. Results: In our series of 14 operated cases, all flaps survived. All the flaps were islanded over the skeletonized facial artery and vein. Tip necrosis occurred in one case. The donor site was closed primarily in all cases. The average speech scoring was grade five, Vancouver scar score of the flap donor area was 2.5 and intelligible speech was difficult in only three cases in follow up. Conclusion: We found this flap useful for reconstruction of small to moderate size defects of oral malignancy following excision with acceptable aesthetic and functional outcome in most of the patients.

Depth of Invasion in Early Oral Cancer: Is 4MM a Threshold for Elective Neck Dissection?

Lymph node metastasis is one of the most important prognostic factors in oral squamous cell carcinoma. In early stage oral cancers, Depth of invasion (DOI) is a predictor for lymph node metastasis. The aim of this study was to evaluate if DOI 4 mm can be considered as a threshold for clinical decision making on elective neck dissection (END) in early oral cancer, by assessing the association of DOI and the risk of occult lymph node metastasis in early Oral squamous cell carcinoma (OSCC). A retrospective study was conducted on 319 patients with early pT1-2 OSCC who were clinically N negative. All patients underwent primary resection and END. The patients were divided into two groups based on DOI: < 4 mm and ≥ 4 mm. Nodal metastases were then noted for each group. The rate of nodal metastasis in respect to tumor size was also observed. Out of 111 patients having DOI < 4 mm only 15 (4.7%) had lymph node metastasis, whereas out of 208 patients having DOI ≥ 4 mm, 81 patients (25.4%) had neck node metastasis, with p value < 0.05. Tumors having DOI ≥ 4 mm has higher chances of occult metastasis and also increased probability of other prognostic factors like PNI and LVI, suggesting that DOI ≥ 4 mm can be considered a cut - off value for performing END.

Serum Concentration of MMP-9 as a Predictive Biomarker for the Progression of Oral Cancer.

Background: Oral cancer is the most prominent cancer subtype among all head and neck cancers, the incidence and prevalence of which has been consistently increasing in past years around the globe. At advanced stages, oral cancer imparts significant mortality, morbidity, and mutilation among the patients, and therefore, diagnosis and treatment of the disease at early stages are considered the optimum strategy for the management of the disease. Since molecular changes appear earlier than physical symptoms, several molecular biomarkers are currently being investigated for their role in diagnosing and treating disease. MMP-9 belongs to the family of proteinases that are involved in cytoskeletal degradation, which is a crucial phase of cancer progression. Objective: In the present study, we analyzed the serum concentration of MMP-9 in oral cancer patients and tried to establish MMP-9 as a predictive biomarker for the progression of oral cancer. We also correlated the clinical, sociodemographic and biochemical parameters with the serum concentration of MMP-9 in oral cancer patients. Methods: Serum was extracted from the blood sample of 38 oral cancer patients and was analyzed for the concentration of MMP-9 using sandwiched ELISA. Predesigned proforma was used to capture the clinical, sociodemographic and biochemical parameters. Unpaired t-test was used to compare two means, one way ANOVA was used to compare more than two means and Pearson's correlation was used to correlate the variables. Results: The mean concentration of MMP-9 in patients of oral cancer was 816.9 ± 236.1 ng/mL. The MMP-9 expression level was higher at advanced oral cancer stages than in the early stages. No significant difference in the MMP expression was found in terms of sociodemographic risk factor and tumor site. MMP-9 exhibit significant negative correlation with the HDL and significantly positive correlation with the PTI. Rest of the biochemical parameters does not exhibit significant correlation. Conclusion: The present study suggests that serum concentration of MMP-9 can be a predictive biomarker for the progression of oral cancer, which needs to be validated by performing further longitudinal cross-sectional studies by taking ample sample size.

Oral cavity obliteration is a novel predictor of functional outcomes after glossectomy reconstruction.

OBJECTIVES: The primary goal for reconstruction of oral tongue defects is to improve speech and swallowing. The purpose of this study is to present a new reconstructive metric that uses volume displacement to measure oral cavity obliteration and correlate this metric to outcomes of speech and swallowing. METHODS: 47 patients underwent resection and primary closure or free-tissue reconstruction of oral tongue defects. Oral cavity obliteration was measured using a novel oral volume assessment test (OVAT). Briefly, a latex balloon filled with pudding was placed on the patient's tongue and patients performed mouth closure to expel the pudding. Residual volumes represented dead space in the oral cavity and was measured by water displacement. These results were correlated with the Speech and Swallowing Assessment and Assessment of Intelligibility of Dysarthric Speech (AIDS) instruments. RESULTS: The mean residual volume was 7.4 cc (range 3 - 20 cc; sd 4.5 cc). There was a correlation with lower residual volumes (better obliteration) with increasing AIDS efficiency ratio (R = 0.72, p < 0.001). A receiver operator curve was used to identify 10 cc of residual volume as the optimal cutoff point. Binary logistic regression using this cut point showed that residual volume significantly predicts normal nutritional mode (p < 0.001), ability to tolerate all liquids (p = 0.007), range of solids (p = 0.004), eating in public (p = 0.007), understandability (p < 0.001), and speaking in public (p = 0.01). CONCLUSIONS: Oral volume assessment test (OVAT) is a novel measure of residual volume (obliteration) that correlates with improved speech efficiency, intelligibility, speaking in public and swallowing outcomes.

A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia.

Oral leukoplakia (OL) has an inherent disposition to develop oral cancer. OL with epithelial dysplasia (OED) is significantly likely to undergo malignant transformation; however, routine OED assessment is invasive and challenging. This study investigated whether a deep learning (DL) model can predict dysplasia probability among patients with leukoplakia using oral photographs. In addition, we assessed the performance of the DL model in comparison with clinicians' ratings and in providing decision support on dysplasia assessment. Retrospective images of leukoplakia taken before biopsy/histopathology were obtained to construct the DL model (n = 2,073). OED status following histopathology was used as the gold standard for all images. We first developed, fine-tuned, and internally validated a DL architecture with an EfficientNet-B2 backbone that outputs the predicted probability of OED, OED status, and regions-of-interest heat maps. Then, we tested the performance of the DL model on a temporal cohort before geographical validation. We also assessed the model's performance at external validation with opinions provided by human raters on OED status. Performance evaluation included discrimination, calibration, and potential net benefit. The DL model achieved good Brier scores, areas under the curve, and balanced accuracies of 0.124 (0.079-0.169), 0.882 (0.838-0.926), and 81.8% (76.5-87.1) at testing and 0.146 (0.112-0.18), 0.828 (0.792-0.864), and 76.4% (72.3-80.5) at external validation, respectively. In addition, the model had a higher potential net benefit in selecting patients with OL for biopsy/histopathology during OED assessment than when biopsies were performed for all patients. External validation also showed that the DL model had better accuracy than 92.3% (24/26) of human raters in classifying the OED status of leukoplakia from oral images (balanced accuracy: 54.8%-79.7%). Overall, the photograph-based intelligent model can predict OED probability and status in leukoplakia with good calibration and discrimination, which shows potential for decision support to select patients for biopsy/histopathology, obviate unnecessary biopsy, and assist in patient self-monitoring.

Spatial Transcriptomics Unravel the Tissue Complexity of Oral Pathogenesis.

Spatial transcriptomics (ST) is a cutting-edge methodology that enables the simultaneous profiling of global gene expression and spatial information within histological tissue sections. Traditional transcriptomic methods lack the spatial resolution required to sufficiently examine the complex interrelationships between cellular regions in diseased and healthy tissue states. We review the general workflows for ST, from specimen processing to ST data analysis and interpretations of the ST dataset using visualizations and cell deconvolution approaches. We show how recent studies used ST to explore the development or pathogenesis of specific craniofacial regions, including the cranium, palate, salivary glands, tongue, floor of mouth, oropharynx, and periodontium. Analyses of cranial suture patency and palatal fusion during development using ST identified spatial patterns of bone morphogenetic protein in sutures and osteogenic differentiation pathways in the palate, in addition to the discovery of several genes expressed at critical locations during craniofacial development. ST of salivary glands from patients with Sjögren's disease revealed co-localization of autoimmune antigens with ductal cells and a subpopulation of acinar cells that was specifically depleted by the dysregulated autoimmune response. ST of head and neck lesions, such as premalignant leukoplakia progressing to established oral squamous cell carcinomas, oral cancers with perineural invasions, and oropharyngeal lesions associated with HPV infection spatially profiled the complex tumor microenvironment, showing functionally important gene signatures of tumor cell differentiation, invasion, and nontumor cell dysregulation within patient biopsies. ST also enabled the localization of periodontal disease-associated gene expression signatures within gingival tissues, including genes involved in inflammation, and the discovery of a fibroblast subtype mediating the transition between innate and adaptive immune responses in periodontitis. The increased use of ST, especially in conjunction with single-cell analyses, promises to improve our understandings of craniofacial development and pathogenesis at unprecedented tissue-level resolution in both space and time.

Awareness and Knowledge of Tobacco Use and Its Relation to Oral Cancer Among Patients Visiting Stomatology Teaching Hospital.

Background: Oral cancer (OC) is a major global health issue, with tobacco use being one of the most significant preventable risk factors. Despite its strong association with OC, public awareness about the harmful effects of tobacco remains limited. This study aims to evaluate the awareness and knowledge of tobacco use related to oral cancer among patients referred to the Stomatology Teaching Hospital. Methods: A cross-sectional survey was conducted at the Stomatology Teaching Hospital of Kabul University of Medical Sciences (KUMS) between January 1 and July 30, 2023. Using a convenience sampling method, the study included 435 patients aged 15 to 76 years. Logistic regression analysis was employed to determine factors associated with tobacco use, and the data were analyzed using SPSS version 26.0. Results: Participants were divided into two groups: tobacco users and non-tobacco users. Most of them were young (18 to 30 years old) with a significant difference in oral cancer knowledge between the two groups (p < 0.001). Cigarettes were the most common tobacco type among users (62.1%), which was also statistically significant (p < 0.001). Tobacco users were 3.04 times more likely to have knowledge about oral cancer (OR: 3.04, p < 0.001, 95% CI: 1.93-4.80), indicating a significant association. Conclusion: The study reveals a general lack of awareness about oral cancer in our study population, particularly regarding specific risk factors. To improve awareness, it is essential for both public awareness campaigns and dentists to play a more active role in educating the public about oral cancer.

Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction.

Introduction: Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma - OSCC) and distant (pancreatic adenocarcinoma - PDAC; malignant melanoma brain metastasis - MBM) cancer origin on NOFs and their possible change into a CAF-like direction. Methods: The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the well-established CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied. Results: Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure. Conclusion: The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.

Integrated analysis of gene expressions and targeted mirnas for explaining crosstalk between oral and esophageal squamous cell carcinomas through an interpretable machine learning approach.

This study explores the bidirectional relation of esophageal squamous cell carcinoma (ESCC) and oral squamous cell carcinoma (OSCC), examining shared risk factors and underlying molecular mechanisms. By employing random forest (RF) classifier, enhanced with interpretable machine learning (IML) through SHapley Additive exPlanations (SHAP), we analyzed gene expression from two GEO datasets (GSE30784 and GSE44021). The GSE30784 dataset comprises 167 OSCC samples and 45 control group, whereas the GSE44021 dataset encompasses 113 ESCC samples and 113 control group. Our analysis led to identification of 20 key genes, such as XBP1, VGLL1, and RAD1, which are significantly associated with development of ESCC and OSCC. Further investigations were conducted using tools like NetworkAnalyst 3.0, Single Cell Portal, and miRNET 2.0, which highlighted complex interactions between these genes and specific miRNA targets including hsa-mir-124-3p and hsa-mir-1-3p. Our model achieved high precision in identifying genes linked to crucial processes like programmed cell death and cancer pathways, suggesting new avenues for diagnosis and treatment. This study confirms the bidirectional relationship between OSCC and ESCC, laying groundwork for targeted therapeutic approaches. This study helps to identify shared biological pathways and genetic factors of these conditions for designing personalized medicine strategies and to improve disease management.

Advances in Raman spectroscopy for characterising oral cancer and oral potentially malignant disorders.

Oral cancer survival rates have seen little improvement over the past few decades. This is mainly due to late detection and a lack of reliable markers to predict disease progression in oral potentially malignant disorders (OPMDs). There is a need for highly specific and sensitive screening tools to enable early detection of malignant transformation. Biochemical alterations to tissues occur as an early response to pathological processes; manifesting as modifications to molecular structure, concentration or conformation. Raman spectroscopy is a powerful analytical technique that can probe these biochemical changes and can be exploited for the generation of novel disease-specific biomarkers. Therefore, Raman spectroscopy has the potential as an adjunct tool that can assist in the early diagnosis of oral cancer and the detection of disease progression in OPMDs. This review describes the use of Raman spectroscopy for the diagnosis of oral cancer and OPMDs based on ex vivo and liquid biopsies as well as in vivo applications that show the potential of this powerful tool to progress from benchtop to chairside.

The impact of different timing of mouth opening exercises on trismus in postoperative radiotherapy patients with oral cancer.

OBJECTIVE: To compare the effects of starting mouth opening exercises at two different times on trismus in postoperative radiotherapy patients with oral cancer. METHODS: Through a prospective randomized controlled trial, purposive sampling was used to select 76 patients undergoing postoperative radiotherapy for oral cancer from March 2023 to January 2024 at the Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Patients were randomly divided into an experimental group (n = 38) and a control group (n = 38) using a random number table at a ratio of 1:1. The experimental group began mouth opening exercises in the second week after surgery (before radiotherapy), while the control group began in the fourth week after surgery (at the start of radiotherapy). The primary outcome measure was maximum interincisal opening (MIO). Secondary outcome measures included pain visual analog scale (VAS) scores and quality of life scores (UW-QOL), assessed at baseline, the second week post-surgery (before radiotherapy), the fourth week post-surgery (at the start of radiotherapy), the ninth week post-surgery (end of radiotherapy), and the twelfth week post-surgery (three weeks after the end of radiotherapy). RESULTS: A total of 72 patients completed all assessments, with 36 in each group, resulting in an overall sample attrition rate of 5.26 % (less than 15 %). There were no statistically significant differences in general demographic and clinical characteristics between the two groups. Repeated measures ANOVA showed significant differences in MIO, VAS, and UW-QOL scores between groups, over time, and in group-time interactions (P < 0.001). From the fourth week post-surgery (at the start of radiotherapy), the experimental group had significantly higher MIO (P < 0.001), significantly lower VAS scores (P < 0.001), and significantly higher UW-QOL scores (P < 0.001) compared to the control group. These differences persisted at subsequent assessment points. CONCLUSION: Initiating mouth opening exercises in the second week post-surgery (before radiotherapy) can significantly improve mouth opening, reduce pain, and enhance the quality of life in postoperative radiotherapy patients with oral cancer. This provides important evidence for clinical practice, although further research is needed to verify the long-term effects.