A Novel Fibrosis-Integrated Nomogram for Predicting Survival in Oral Squamous Cell Carcinoma Patients with Oral Submucous Fibrosis: A Retrospective Cohort Study.

Differential expression of programmed death-1 and its ligand, programmed death ligand-1 in oral squamous cell carcinoma with and without oral submucous fibrosis

To assess extracellular matrix changes among oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients using special histochemical stains. Twenty biopsy specimens of OSMF and 30 biopsy specimens of OSCC were included in the present study. Among 20 OSMF specimens, 10 were of early OSMF and the remaining 10 were of advanced OSMF. Out of 30 OSCC specimens, 10 cases each were of well-differentiated OSCC, moderately differentiated OSCC and poorly differentiated OSCC. Three sections, each 4 μm thick, were obtained from all specimens. One section was stained with routine H&E staining, whereas the other section was stained with Masson's trichrome (MT) stain for collagen and Verhoeff-Van Gieson (VVG) for elastic fibres. Evaluation of all specimens was performed under the light microscope. The arrangement of collagen fibres and elastic fibres was compared between the OSMF group and OSCC group, in between different grades of OSMF and in between different grades of OSCC. The results were evaluated using SPSS software. Early OSMF cases were associated with fibrosis in the superficial lamina propria, whereas advanced OSMF had fibrosis involving deeper muscle fibres. In all early OSMF cases, elastic fibres were arranged in thin bundles, whereas in advanced OSMF cases, elastic fibres were in thick bundles. In well- and moderately differentiated OSCCs, the collagen fibres were arranged in thick bundles and in poorly-differentiated OSCCs, the collagen fibres appeared to be fragmented. The elastic fibres in well-differentiated OSCC and moderately-differentiated OSCC were thickly arranged, and poorly-differentiated OSCC showed thin fibres and 70% of cases showed the absence of elastic fibres. Changes observed in both collagen and elastic fibres in the extracellular matrix (ECM) can be taken as a study model to further understand the progression of OSMF to OSCC using histochemical stains.

Context: Trace elements such as copper (Cu) and zinc (Zn) are involved in vital biochemical reactions, including different redox reactions and free radical formation and in maintaining cellular homeostasis. Several studies have been carried out on Cu, Zn, and iron level in the serum, plasma, and tissue of oral pre-malignant and malignant lesions. Aim: The aim of this study was the estimation and comparison of serum levels of Cu, Zn, and Cu/Zn ratio in oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients. Subjects and Methods: Sera of OSMF (n = 30) and OSCC (n = 30) patients as also of healthy controls was analyzed for the estimation of Cu and Zn using atomic absorption spectrophotometry. Statistical Analysis: Analysis of variance was used to compare the results of patients of OSMF, OSCC patients, and the controls. Independent sample's t-test was used to compare the mean values between the two groups. Comparison of mean values between different groups was carried out using Student's t-test using appropriate level of significance and degrees of freedom. Results: Sera levels of Cu were found to be increased while those of Zn were decreased in OSMF and OSSC patients as compared to the healthy controls. Conclusion: It could be concluded that altered sera levels of these trace elements can be helpful in early detection, management, and monitoring the efficacy of treatment in OSMF and OSCC patients.

This study investigates nutritional deficiencies as potential markers in the development of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs), including oral submucous fibrosis (OSMF). OSMF, linked to betel nut product use, has been rising in India. This study focuses on assessing iron, vitamin B12, and folate deficiencies in OSMF and OSCC patients as indicators of disease progression and potential markers. Participants from different groups were recruited and examined. Vitamin B12 and folate levels were measured using enzyme-linked immunosorbent (ELISA) assays, whereas serum iron and total iron-binding capacity (TIBC) were analyzed using clinical chemistry techniques. Statistical analyses were performed to compare these markers between groups. Vitamin B12 and folate levels exhibited notable reduction in OSCC and OSMF patients in comparison to controls. Serum iron showed a decreasing trend, with no statistical significance. TIBC also exhibited variation among groups. Vitamin B12, folate, and serum iron deficiencies were observed in OSMF and OSCC patients, potentially indicating their role in disease progression. Collagen metabolism and iron utilization were suggested as mechanisms for these deficiencies. Nutritional deficiencies, particularly vitamin B12 and folate, appear to be associated with OSMF and OSCC, potentially serving as markers for disease progression. This study underscores the importance of assessing these deficiencies as predictive indicators in diagnosing and managing OSCC and OPMDs. Additional investigation is necessary to substantiate and broaden the scope of these findings.

Oral squamous cell carcinoma (OSCC) often presents with unsatisfactory survival outcomes, especially in advanced stages. This study aimed to develop and validate a nomogram incorporating demographic, clinicopathologic, and treatment-related factors to improve the prediction of overall survival (OS) in OSCC patients. Data from 15,204 OSCC patients in a US database were retrospectively utilized to construct a prognostic model and generate a nomogram. External validation was performed using an independent cohort of 359 patients from a specialized cancer center in China. Prognostic factors were identified using Cox regression analysis and incorporated into the nomogram. Model performance was evaluated by concordance index (C-index), time-dependent area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). A risk stratification system was developed to classify patients into high- and low-risk groups. Age, sex, primary tumor site, T and N staging, and treatment modalities (including surgery, chemotherapy, and radiotherapy) were found to be independent prognostic factors. The nomogram achieved a C-index of 0.727 in the training set and 0.6845 in the validation set, outperforming the conventional TNM staging system. The nomogram's superior predictive accuracy was confirmed by higher AUC values, better calibration, and improved clinical utility as demonstrated by DCA. Risk stratification, based on the nomogram, distinguished patients into distinct prognostic groups with significant OS differences. This nomogram provides an effective, personalized tool for predicting OS in OSCC. It offers clinicians a valuable aid for treatment decision-making and improves patient management.

The aim of our study was to determine the impact of Th17/Treg imbalance on the progression and malignant transformation of oral submucosal fibrosis (OSF). To assess Th17 and Treg expression, overall 52 peripheral blood samples from OSF, oral squamous cell carcinoma (OSCC) patients, and healthy donors were analyzed by flow cytometry. Thirty normal oral mucosa, 72 OSF, and 90 OSCC samples were analyzed by immunohistochemistry. In peripheral blood samples, in OSCC with OSF, Th17 and Treg expression were significantly higher than those in OSF and OSCC without OSF as confirmed by immunohistochemistry. During OSF progression, Th17 and Th17/Treg ratio showed an increasing trend, while Treg expression showed a decreasing trend. Treg expression was significantly higher in OSCC with OSF than in OSF and OSCC without OSF, whereas the Th17/Treg ratio was significantly lower in OSCC with OSF. Treg expression was significantly correlated with smoking and clinical stage. Th17/Treg ratio was significantly associated with tumor size, lymph node metastasis, and clinical stage. A low Th17/Treg ratio was significantly associated with poor prognosis. Th17/Treg ratio is a potential diagnostic indicator for OSF occurrence and malignant transformation and was an independent prognostic factor for OSCC.

Objectives:Oral Submucous Fibrosis (OSMF) is potentially malignant disorder known to transform into oral cancer. The aim of this study is to determine the degree and pattern of expression of aberrant Ki67 in OSMF, oral squamous cell carcinoma (OSCC) and in normal oral mucosa patients (NOM). The objective is to correlate between Ki67 expression and degree of dysplasia in OSMF patents and also Ki67 expression with clinical and histological grading of OSMF and OSCC patient. Materials and Methods:A prospective cross-sectional study was conducted with purposive sampling technique from Jan 2017 to April 2020.The study groups consist of 35 OSMF cases, 10 cases of each OSCC and NOM. The samples were immunohistochemically analyzed for expression Ki67 antigen using chi-square test (P < 0.05).Results:The expression of Ki67 was significantly higher in OSMF than that of NOM samples, but less than that of OSCC samples. Present study showed correlation between expression of Ki67 with clinical staging and histological grading both in OSMF and OSCC patients. Conclusion:The study demonstrated a high incidence of Ki67 over expression in, OSMF and OSCC. Hence, Ki-67 can be widely used as a proliferation marker to measure growth fraction of cells in OSMF and also for determining the severity of epithelial dysplasia.

To investigate the predictive value of serum soluble T-cell immunoglobulin and mucin domain-3 (sTIM-3), transforming growth factor-beta 1 (TGF-β1), and vasohibin-1 in the lymphatic metastasis of oral squamous cell carcinoma (OSCC). A total of 220 OSCC patients admitted to Shanxi Provincial Cancer Hospital between January 2022 and December 2024 were included in this retrospective study. The patients were divided into training and validation sets at a 7:3 ratio (154 and 66 patients, respectively). Baseline characteristics, blood test results, and tumor marker levels were compared between the two groups. Predictors were screened, and column-line graphical models were constructed using Least Absolute and Residual Selection Operator (LASSO) regression and multifactorial logistic regression. The performance of the model was then evaluated using ROC curves, calibration curves, and decision curve analysis. LASSO regression identified the following variables as predictors: clinical stage, tumor diameter, squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen, sTIM-3, TGF-β1, and vasohibin-1. Multifactorial logistic regression analysis revealed that clinical stage, SCC-Ag, sTIM-3, TGF-β1, and vasohibin-1 were independent predictors of lymphatic metastasis. The AUC of the nomogram model was 0.868 in the training set and 0.863 in the validation set, indicating strong discriminatory ability. Calibration curves showed good agreement between predicted and actual values, with p-values for goodness of fit of 0.865 (training set) and 0.872 (validation set). Decision curve analysis demonstrated significant clinical benefit, with maximum benefit rates of 39.41% in the training set and 37.80% in the validation set. sTIM-3, TGF-β1, and vasohibin-1, along with clinical stage and SCC-Ag, are independent predictors of lymph node metastasis in OSCC patients. The risk prediction model based on these variables demonstrates strong predictive ability.

Background and Objectives: Unusual dermatoglyphics may indicate genetic or chromosomal aberrations consistent with numerous diseases. The aim of the present study was to relate dermatoglyphic patterns in oral leucoplakia, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients. Aim: The aim of the present study was to analyse the qualitative and quantitative variations in digital and palmar dermatoglyphics amongst the patients diagnosed with oral leucoplakia, OSMF and OSCC. Materials and Methods: A cross-sectional study comprising 225 patients, of which 75 patients were diagnosed with oral leucoplakia and OSMF, 75 patients were diagnosed with OSCC whereas 75 high-risk individuals with habits but without active lesions, was carried out. Finger and palmar prints were collected and analysed qualitatively and quantitatively. Results: In oral leucoplakia, OSMF and OSCC patients, loops were found to be the predominant finger ridge patterns whereas whorls were predominant in the control group. Conclusion: The study concluded that dermatoglyphics might serve as a potential tool in the early detection of the various oral pre-malignant and malignant lesions.

Context:Oral submucous fibrosis (OSF) is strongly associated with areca nut usage; the existence of OSF in patients with oral squamous cell carcinoma (OSCC) is an indicator of areca nut-induced carcinogenesis. As areca nut follows a discrete molecular path for oral carcinogenesis, this could be the basis why OSCC patients with OSF are different and are currently projected to constitute a distinct clinicopathologic entity.Aim:This study aims to analyze and compare the demographics, risk factors and clinicopathologic features of OSCC patients with and without OSF.Materials and Methods:A retrospective review of OSCC cases treated in the institution from 2008 to 2013 was done. Sixty OSCC of buccal mucosa were selected, of which 30 were with concomitant OSF and 30 without OSF. Demographics, risk factors and clinicopathological features were studied. The data were analyzed by SPSS-20 software, using the Pearson Chi-square, Fisher's exact and Mann–Whitney U-tests.Results:OSCC cases with OSF were younger (mean age 40.5 vs. 54 years) compared to those without OSF (P < 0.05). Risk factors and other clinicopathological parameters did not differ between the two groups. There was significant difference in the two groups with regard to tumor differentiation (P = 0.000). Tumors in OSCC with OSF were more likely to be well differentiated.Conclusion:Although majority of OSCC patients with OSF were young with a better grade of tumor differentiation, other clinicopathologic features having prognostic significance did not differ significantly between the two groups. Therefore, OSCC arising in background OSF as a distinct entity is uncertain.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in Southern and Southeastern Asia, and in the Hunan region of China, where betel nut chewing is prevalent. The prognosis of OSCC with oral submucous fibrosis (OSF), caused by areca nut use, remains debated. This study aimed to determine whether OSCC associated with OSF exhibits distinct tumor biological behaviors compared to OSCC without OSF, and to explore the tumor immune microenvironment, specifically focusing on the expression of Th17/Treg cells and the PD-1/PD-L1 axis. OSCC patients with and without OSF (Jan 2013-Oct 2023) were recruited from Xiangya Stomatological Hospital, grouped by history and clinical features. Patients were followed every 3months for recurrence and complications. SPSS 27 was used for descriptive and inferential statistics (Kaplan-Meier, Cox regression, χ2-test); survival/log survival/hazard functions were plotted to compare survival probabilities, stratified by sex, age, tumor location, stage (early/advanced, TNM), and habits (betel quid, smoking, alcohol). A subgroup of 88 patients (44 each) had immunohistochemical analysis for Th17/Treg and PD-1/PD-L1 expression. OSCC with OSF primarily affected the tongue and buccal mucosa, occurring in younger patients (median age 48 vs. 55years). Recurrence was higher in OSF-associated OSCC (27.56% vs. 19.73%). Overall Survival (OS) rates for OSCC with OSF were 94.25% (1-year OS), 49.82% (3-year OS), and 41.23% (5-year OS), compared to 94.82% (1-year OS), 56.58% (3-year OS), and 47.92% (5-year OS) in non-OSF cases. A subgroup of 88 patients (44 each) had immunohistochemical analysis for the expression of IL-17 (a marker of Th17 cells) and Foxp3 (a marker of Treg cells), as well as PD-1/PD-L. Immune profiling showed elevated IL-17, Treg cells, PD-L1, and PD-1 in OSF-associated OSCC. OSCC with OSF displays more aggressive tumor biological behavior and worse prognosis, which contributed by a more suppressive immune microenvironment marked by elevated levels of IL-17, Treg cells, and PD-1/PD-L1 expression. These results highlight the need for tailored treatment approaches in managing OSCC in patients with OSF.

Oxidative stress is a recognized factor that poses a significant risk for the development of Oral Squamous Cell Carcinoma (OSCC) and Oral Submucous Fibrosis (OSMF), as it leads to the generation of Reactive Oxygen Species. In recent years, there has been significant research on the enzymes MDA (malondialdehyde) and SOD (superoxide dismutase), investigating their potential role in the development of OPMD and OSCC. These enzymes have emerged as promising biomarkers due to their ability to provide a less invasive, cost-effective, and objective diagnostic method. Furthermore, they can be used to monitor disease progression and assess the effectiveness of therapy. The aim of this study was to assess the levels of MDA and SOD in the serum of patients diagnosed with OSCC and OSMF. Study group comprised of 60 patients, out of which 20 cases of clinically diagnosed OSCC patients and 20 cases of OSMF and 20 cases pf control comprising of healthy patients were recruited. Estimation MDA and SOD was done by ELISA. The statistical analysis was done using SPSS analysis. When comparing the levels of MDA and SOD between the OSCC and OSMF groups and the control group, statistically significant findings indicated elevated levels of malondialdehyde and reduced levels of superoxide dismutase in both the OSCC and OSMF groups. In this study, the assessment of lipid peroxidation through MDA levels revealed elevated concentrations in both the OSCC and OSMF groups when compared to the control group. Specifically, the order of MDA levels was observed as OSCC > OSMF > Control. Conversely, antioxidant enzyme levels, such as SOD, exhibited decreased concentrations in the OSCC and OSMF groups compared to the control group, with the order of SOD levels being Control > OSMF > OSCC. Consequently, the findings suggest that MDA and SOD can be considered potential biomarkers for identifying and monitoring OSCC and OSMF diseases.

Nodal involvement in Oral Squamous Cell Carcinoma (SCC) patients with and without Oral Sub Mucous Fibrosis (OSMF): A Comparative Study

Susceptibility associations of HLA class II gene polymorphisms in oral submucous fibrosis derived oral squamous cell carcinoma.

Oral submucous fibrosis (OSMF) is one of the common oral potentially malignant disorders characterized by reduced mouth opening and burning sensation. Complete clinical examination in patients with OSMF is challenging due to insufficient mouth opening, leading to incomplete diagnosis and subsequently erroneous treatment execution. This study aimed to assess the incidence of oral squamous cell carcinoma (OSCC) in OSMF patients and to determine the need of an imaging modality like contrast-enhanced computed tomography (CECT) scan for a complete diagnosis of known OSMF patients with any hidden malignant lesion. The primary outcome was incidence of OSCC in patients of OSMF. The secondary outcomes were age, gender, grading of OSMF and presence of any associated other premalignant lesion and lymph node status. A p value < 0.05 was considered as significant. Out of the 230 OSMF patients screened, 150 patients fulfilled the criteria and underwent CECT scan. The incidence of OSCC in OSMF patients was found to be 14.7% (n = 22). The authors conclude that it is essential to recognize that a significant number of OSCC cases (n = 22) may be concealed under the pretext of OSMF, thus highlighting the importance of CECT scan in patients of OSMF for early diagnosis and prompt treatment.