Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Tumours of the Oral Cavity and Mobile Tongue.

The fifth chapter of the upcoming fifth edition of the 2022 World Health Organization Classification of Tumours of the Head and Neck titled Tumours of the oral cavity and mobile tongue, has had some modifications from the 2017 fourth edition. A new section "Non-neoplastic Lesions", introduces two new entries: necrotizing sialometaplasia and melanoacanthoma. The combined Oral potentially malignant disorders and Oral epithelial dysplasia section in the 2015 WHO has now been separated and submucous fibrosis and HPV-associated dysplasia are also discussed in separate sections. Carcinoma cuniculatum and verrucous carcinoma are described in dedicated sections, reflecting that the oral cavity is the most common location in the head and neck for both these entities which have distinct clinical and histologic features from conventional squamous cell carcinoma. This review summarizes the changes in Chapter 5 with special reference to new additions, deletions, and sections that reflect current clinical, histological, and molecular advances.

Oral submucous fibrosis: An overview of a challenging entity.

The oral cavity is considered to be a mirror of the body's health, as it reflects the manifestations of various systemic disorders. Most of the oral mucosa is derived embryologically from an invagination of ectoderm and thus, like other similar orifices, it may become involved in the disorders that are primarily associated with the skin. Oral submucous fibrosis is one of the commonest precancerous conditions of the oral mucosa involving any part of the oral cavity resulting in tissue scarring, dysphagia and trismus. It is a collagen-related disorder characterized by excessive fibrosis in the oral submucosa, hyalinization and degenerative changes in the muscles. This disease has become a challenging entity for dermatologists due to resemblance of its features to various mucocutaneous conditions. An improper diagnosis can lead to wrong treatment and additional complications. Dermatologists need to be aware of the characteristic features of this disease which can distinguish it from other similar conditions. This review aims to focus on the detailed aspects of oral submucous fibrosis including its historical background, etiological factors, pathogenesis, clinical features, differential diagnosis, investigations, management and future perspectives.

TFM classification and staging of oral submucous fibrosis: A new proposal.

BACKGROUND: We have evaluated the rationale of existing grading and staging schemes of oral submucous fibrosis (OSMF) based on how they are categorized. A novel classification and staging scheme is proposed. METHODS: A total of 300 OSMF patients were evaluated for agreement between functional, clinical, and histopathological staging. Bilateral biopsies were assessed in 25 patients to evaluate for any differences in histopathological staging of OSMF in the same mouth. Extent of clinician agreement for categorized staging data was evaluated using Cohen's weighted kappa analysis. Cross-tabulation was performed on categorical grading data to understand the intercorrelation, and the unweighted kappa analysis was used to assess the bilateral grade agreement. Probabilities of less than 0.05 were considered significant. Data were analyzed using SPSS Statistics (version 25.0, IBM, USA). RESULTS: A low agreement was found between all the stages depicting the independent nature of trismus, clinical features, and histopathological components (K = 0.312, 0.167, 0.152) in OSMF. Following analysis, a three-component classification scheme (TFM classification) was developed that describes the severity of each independently, grouping them using a novel three-tier staging scheme as a guide to the treatment plan. CONCLUSION: The proposed classification and staging could be useful for effective communication, categorization, and for recording data and prognosis, and for guiding treatment plans. Furthermore, the classification considers OSMF malignant transformation in detail.

Estimation of copper in saliva and areca nut products and its correlation with histological grades of oral submucous fibrosis.

BACKGROUND: The purpose of this study was to estimate the copper levels in saliva of patients with oral submucous fibrosis (OSF) and different areca nut products and its correlation with different histological grades of OSF. METHODS: The study comprised 60 individuals, 30 OSF patients and 30 non-OSF individuals. Unstimulated whole saliva was collected, and copper analysis was performed using colorimetric method. The commercial areca nut products used by the patients were acquired and subjected to copper analysis through the atomic absorption spectrophotometer method. Oral biopsies were performed for OSF patients for histopathological correlation. RESULTS: The mean salivary copper level was 27.023 µg/dl in OSF patients when compared with 8.393 µg/dl in non-OSF individuals (P < 0.005). The mean copper content in different areca nut products was 13.313 ppm (P < 0.005). Comparison of copper content in different areca nut products with salivary copper levels of OSF patients showed negative correlation (P < 0.853). Comparison of salivary copper levels between different histological grades of OSF yielded a statistically significant association between grades I and III (P < 0.005) and grades II and III OSF (P < 0.019). Comparison of copper content in areca nut products and different histological grades of OSF yielded weak negative statistical correlation (r = -0.116). CONCLUSION: Despite high copper content in areca nut products, the observations yielded a negative correlation with different histological grades of OSF. This further raises a doubt about the copper content in areca nut as an etiological factor for this crippling disease.

Oral submucous fibrosis--a treatment protocol based on clinical study of 100 patients in central India.

PURPOSE: Oral submucous fibrosis till date is a very poorly understood and unsatisfactorily treated disease with variable signs and symptoms. In this paper, we have classified the disease in different groups according to the clinical signs, radiological assessment, histopathological confirmation, progress, and severity of disease and proposed a treatment algorithm for effective treatment of the disease in 100 patients. MATERIAL AND METHOD: In our study, we randomly selected 100 patients of oral submucous fibrosis and classified them in to five groups based on clinical symptoms and radiological and histopathological parameters. We have given specific treatment for each group and followed them up for 2 years regularly. RESULTS: We found that almost all patients got symptomatic relief from the disease. Patient's interincisal mouth opening increased significantly. All patients can take regular diet. Progressive malignant transformation can be detected earlier to avoid future morbidity and mortality. CONCLUSION: Oral submucous fibrosis (OSMF) scoring index is very effective to decide the severity of disease and progress. Based on this scoring and grouping we can give definite prompt treatment to the patients with satisfactory results. Such a way this proposed scoring and staging can play major role in controlling and treating this widespread global disease.

Betel nut chewing behaviour and its association with oral mucosal lesions and conditions in Ghaziabad, India.

PURPOSE: To assess the practices and behaviour among Betel nut users in Ghaziabad and to detect the clinically associated oral mucosal lesions and conditions. MATERIALS AND METHODS: A community-based survey was conducted in Ghaziabad among 332 betel nut users. Data on betel nut use was obtained through a self-administered questionnaire. Oral mucosal lesions and conditions were recorded using WHO criteria. RESULTS: Out of 332 betel nut users, 32.8% consumed Gutkha. 62.3% users used betel nut with tobacco. Most of the study population started chewing betel nut because of peer pressure and the habit started at the workplace or school. A majority found that there was no physical discomfort due to the habit. The significant oral diseases detected were oral leukoplakia in 11.7% and oral submucous fibrosis in 6.1% of individuals. CONCLUSION: The findings of the present study revealed that 74.7% of the participants were current chewers. 30.4% of all participants had oral mucosal lesions and conditions.

Morphometric evaluation of soft palate in oral submucous fibrosis--a digital cephalometric study.

The Present study was carried out to evaluate the morphology of soft palate in Oral Submucous Fibrosis (OSF) patients using digital lateral cephalogram. A total number of 70 patients were included in the study (Control group had 35 patients and Study group had 35 OSF patients) were evaluated for soft palate by digital lateral cephalogram. The anterio-posterior length and superior-inferior length of soft palate were measured. The morphology of soft palate was categorized as type 1, to type 6. Different types of soft palate were compared with stages of OSF. Among the Study group (35 patients) 62.9% had Stage 2 OSF. Leaf shaped (Type 1) soft palate was seen commonly in stage 2 OSF whereas butt shaped (Type 3) in stage 3 OSF. In the present study there was statistically significant difference in length (anterio-posterior) of Type 1 soft palate of OSF patients. In the present study as the OSF progressed to advanced stage there was gradual change from Type 1 and Type 2 variety of Soft palate to Type 3 and Type 6 variety of soft palate. The study observed that there was gradual reduction in the length of soft palate in anterior-posterior direction in OSF patients.

Estimation of serum copper and zinc levels in oral submucous fibrosis: an atomic absorption spectroscopic study.

BACKGROUND AND OBJECTIVES: Biochemical derangements of microelements although reported in oral cancer is poorly understood in oral submucous fbrosis (OSMF). Hence, the present study was carried out to estimate and compare the serum copper and zinc levels among different histopathological stages of OSMF with that of healthy controls. MATERIALS AND METHODS: Thirty histopathologically diagnosed cases of OSMF and 30 healthy controls reporting to MS Ramaiah Dental College and Hospital (MSRDCH), Bengaluru, were included in the study. The histopathological staging of OSMF was done as per criteria given by Pindborg and Sirsat (1966). Blood samples were collected and the serum copper and zinc levels were estimated using atomic absorption spectroscopy. The results were statistically analyzed using independent t-test and Kruskal-Wallis test. RESULTS: The mean serum copper levels were increased (p < 0.0005) and zinc levels were decreased (p < 0.01) in OSMF patients when compared to that of controls. The mean serum copper levels showed an increasing trend from stage I to IV (p = 0.004) while zinc levels showed a decreasing trend from stage I to IV (p = 0.04) in OSMF patients. CONCLUSION: The serum copper and zinc levels in OSMF showed a signifcant difference in comparison to that of controls and between the histopathological stages. These fndings indicate that serum copper and zinc may have a contributory role in the etiopathogenesis of OSMF. CLINICAL RELEVANCE: Although the role of the trace elements as etiological factors is minor, derangements noted in the serum copper and zinc levels could be correlated with diseased progression and possibly explain the transformation of OSMF into malignancy. Thus, they can be used as prognostic markers and can be of value for proactive intervention.

Use of buccal fat pad for treatment of oral submucous fibrosis.

PURPOSE: The aim of this study was to clinically evaluate the application of pedicled buccal fat pad (BFP) in the surgical management of stage III and IV oral submucous fibrosis (OSMF). MATERIALS AND METHODS: Twenty-eight cases of clinically and histologically diagnosed cases of OSMF were divided into 2 groups: group I (n = 15) and group II (n = 13), corresponding to clinical stage III and stage IV, respectively. All the patients underwent incision of fibrotic bands and coverage of the buccal defect with a pedicled BFP flap. Both groups were analyzed separately for mouth opening (interincisal distance in millimeters) preoperatively and 1 year postoperatively, time taken for epithelialization of BFP, time taken for establishment of normal contour, and changes in symptoms (painful ulcerations, burning sensation, and intolerance to spices) 1 year after grafting. RESULTS: The mean preoperative mouth opening was 19.6 mm (SD, 2.43) in group I and 12.92 mm (SD, 1.21) in group II. The mean postoperative mouth opening after 1 year was 35 mm in group I (SD, 1.96) and 31.76 mm in group II (SD, 1.97). The time taken for epithelialization of BFP was 4 weeks in group I and 5 weeks in group II. The mean time taken for establishment of normal contour after grafting was 12.25 weeks (SD, 1.42) in group I and 15.07 weeks (SD, 1.26) in group II. In 2 cases in group II, there was remission of painful ulcerations, burning sensation, and intolerance to spices. CONCLUSION: BFP is reliable for the treatment of OSMF.

Statistical analysis of textural features for improved classification of oral histopathological images.

The objective of this paper is to provide an improved technique, which can assist oncopathologists in correct screening of oral precancerous conditions specially oral submucous fibrosis (OSF) with significant accuracy on the basis of collagen fibres in the sub-epithelial connective tissue. The proposed scheme is composed of collagen fibres segmentation, its textural feature extraction and selection, screening perfomance enhancement under Gaussian transformation and finally classification. In this study, collagen fibres are segmented on R,G,B color channels using back-probagation neural network from 60 normal and 59 OSF histological images followed by histogram specification for reducing the stain intensity variation. Henceforth, textural features of collgen area are extracted using fractal approaches viz., differential box counting and brownian motion curve . Feature selection is done using Kullback-Leibler (KL) divergence criterion and the screening performance is evaluated based on various statistical tests to conform Gaussian nature. Here, the screening performance is enhanced under Gaussian transformation of the non-Gaussian features using hybrid distribution. Moreover, the routine screening is designed based on two statistical classifiers viz., Bayesian classification and support vector machines (SVM) to classify normal and OSF. It is observed that SVM with linear kernel function provides better classification accuracy (91.64%) as compared to Bayesian classifier. The addition of fractal features of collagen under Gaussian transformation improves Bayesian classifier's performance from 80.69% to 90.75%. Results are here studied and discussed.

Proposed clinical classification for oral submucous fibrosis.

Oral Submucous Fibrosis (OSMF) is a chronic, progressive, scarring disease, that predominantly affects people of South Asia and South-East Asia, where chewing of arecanut and its commercial preparation is high. Presence of fibrous bands is the main characteristic feature of OSMF. Based on clinical and/or histopathological features of OSMF, various classifications have been put forth till date. But the advantages and drawbacks of these classification supersedes each other, leading to perplexity. Our various studies and clinical experience in the field of OSMF have initiated us to propose/introduce the new clinical classification which could assist the clinician in the categorization of this potentially malignant disorder according to its biological behaviour and hence its subsequent medical and surgical management.

Textural characterization of histopathological images for oral sub-mucous fibrosis detection.

In the field of quantitative microscopy, textural information plays a significant role very often in tissue characterization and diagnosis, in addition to morphology and intensity. The aim of this work is to improve the classification accuracy based on textural features for the development of a computer assisted screening of oral sub-mucous fibrosis (OSF). In fact, a systematic approach is introduced in order to grade the histopathological tissue sections into normal, OSF without dysplasia and OSF with dysplasia, which would help the oral onco-pathologists to screen the subjects rapidly. In totality, 71 textural features are extracted from epithelial region of the tissue sections using various wavelet families, Gabor-wavelet, local binary pattern, fractal dimension and Brownian motion curve, followed by preprocessing and segmentation. Wavelet families contribute a common set of 9 features, out of which 8 are significant and other 61 out of 62 obtained from the rest of the extractors are also statistically significant (p<0.05) in discriminating the three stages. Based on mean distance criteria, the best wavelet family (i.e., biorthogonal3.1 (bior3.1)) is selected for classifier design. support vector machine (SVM) is trained by 146 samples based on 69 textural features and its classification accuracy is computed for each of the combinations of wavelet family and rest of the extractors. Finally, it has been investigated that bior3.1 wavelet coefficients leads to higher accuracy (88.38%) in combination with LBP and Gabor wavelet features through three-fold cross validation. Results are shown and discussed in detail. It is shown that combining more than one texture measure instead of using just one might improve the overall accuracy.

Correlation of salivary and serum IgG, IgA levels with total protein in oral submucous fibrosis.

Oral submucous fibrosis (OSMF) is a disabling, potentially malignant condition of the oral cavity. The aetiology of OSMF is multifactorial but remains obscure. Although arecanut is considered to be the most important causative agent, responses observed in individuals using arecanut vary in relation to quantity and duration. It is considered that an immunological process is responsible for the pathogenesis of disease. We correlated salivary immunoglobulin A (IgA), salivary immunoglobulin G (IgG) and serum immunoglobulin A (IgA), serum immunoglobulin G (IgG), levels by turbidometric immunoassay. We estimated the levels of total serum protein (TSP) and haemoglobin (Hb) to determine the role of nutritional deficiency. The study population comprised 30 cases of OSMF and 10 controls. Five milliliters of blood and 2 ml of saliva were collected. Quantitative analysis of serum and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hb were estimated by Biuret and cyanmethaemoglobin methods, respectively. All patients showed significant (P < 0.01) increase in serum and salivary IgG, IgA levels as compared to controls. TSP patients showed significant (P < 0.01) decrease as compared to controls. Results of Hb in patients were not significant. The estimation of immunoglobulin levels is important to support the concept of autoimmune basis. Estimation of TSP and Hb suggests that nutrition has a definite role in OSMF.

Evaluation of myofibroblasts in oral submucous fibrosis: correlation with disease severity.

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a premalignant condition of the oral cavity characterized by generalized submucosal fibrosis. Myofibroblasts are contractile cells expressing α-smooth muscle actin (α-SMA) and are considered primary producers of extracellular matrix after injury. Their accumulation has been established as a marker of progressive fibrosis in organs like lungs, liver, kidney and skin. This study aims to evaluate the presence of myofibroblasts in various histological stages of OSMF. MATERIALS AND METHOD: Seventy cases of OSMF, which were further categorized histologically into early (35 cases) and advanced (35 cases), were subjected to immunohistochemistry using α-SMA antibody for detection of myofibroblasts. Fifteen normal oral mucosa specimens were also stained as controls. RESULTS: The number of α-SMA-stained myofibroblasts in OSMF was significantly increased when compared to that of the normal controls (P<0.001). Additionally, a statistically significant increase in the myofibroblasts population between early and advanced stages was observed (P=0.000). CONCLUSIONS: Our results corroborate the possibility that OSMF actually represents an abnormal healing process in response to chronic mechanical and chemical irritation because of areca nut chewing as demonstrated by the increased incidence of myofibroblasts in this disease. Furthermore, the progressive increase in myofibroblasts from early to advanced stages suggests their potential use as markers for evaluating the severity of OSMF.

Esophageal changes in oral submucous fibrosis using fiber-optic endoscopy.

AIM: The aim of this study was to determine the extent of esophageal involvement and the association between the clinical and functional stages of oral submucous fibrosis and esophageal changes in oral submucous fibrosis patients. METHODS: Thirty of 35 biopsied patients with proven oral submucous fibrosis, and 20 patients with no evidence of disease, underwent upper gastrointestinal endoscopy. Biopsies were taken from upper third, middle third, and lower third of the esophagus and sent for histopathological evaluation. The esophageal changes in the clinical and functional stages were studied both endoscopically and histopathologically. RESULTS: We found that most patients had blanching in clinical stage 2, functional stage B, and functional stage C. In most patients, blanching was found in the upper third of the esophagus, followed by the middle third and lower third. Fibrosis in the middle third of the esophagus was found in most patients. CONCLUSION: The present study concludes that oral submucous fibrosis is not only confined to the oral cavity, but also extends to the esophagus. We found that there is an inverse relationship between the opening of the mouth and esophageal involvement.

[Potentially malignant disorders of the oral mucosa: terminology and classification]. / Affections potentiellement malignes de la muqueuse buccale: nomenclature et classification.

The last WHO expert workgroup recommended abandoning the distinction between potentially malignant lesions and conditions. The term to use is "potentially malignant disorders". Leukoplakia is the most common of these disorders, while erythroplakia is rather rare. The diagnosis is still made by excluding other documented white or red lesions. Despite progress in molecular biology, no marker allows predicting malignant transformation. These lesions are treated surgically with or without dysplasia. It is unknown if this surgery can really prevent transformation into squamous cell carcinoma. The potential malignancy of oral lichen planus is still debated. The risk of malignant transformation is lower than that of leukoplakia. No treatment may prevent this. Other potentially malignant conditions such as oral submucous fibrosis, actinic cheilitis, lupus, and immunodeficiency are rare.

Survivin as a potential early marker in the carcinogenesis of oral submucous fibrosis.

OBJECTIVE: Oral submucous fibrosis (OSF) is a chronic precancerous condition. Survivin is one of the inhibitors of apoptosis protein, and is focused on owing to its unique therapeutic and prognostic potential. STUDY DESIGN: To determine the potential involvement of survivin in the carcinogenesis of OSF, we analyzed the relationship between the survivin and clinical characteristic. RESULTS: Immunohistochemistry was used to show that survivin expression levels were significantly higher in the oral squamous cell carcinoma transformed from OSF group compared with normal group (P < .01) and OSF group (P < .01). In the different stages of OSF, survivin expression exhibited difference as well. Furthermore, Western blotting and reverse-transcription polymerase chain reaction analysis confirmed the increased expression of survivin in the carcinogenesis of OSF. CONCLUSION: These results suggest that survivin plays an important role during the malignant transformation of OSF and may provide an indication to early prevention and diagnosis in the progression of OSF.

Automated classification of cells in sub-epithelial connective tissue of oral sub-mucous fibrosis-an SVM based approach.

Quantitative evaluation of histopathological features is not only vital for precise characterization of any precancerous condition but also crucial in developing automated computer aided diagnostic system. In this study segmentation and classification of sub-epithelial connective tissue (SECT) cells except endothelial cells in oral mucosa of normal and OSF conditions has been reported. Segmentation has been carried out using multi-level thresholding and subsequently the cell population has been classified using support vector machine (SVM) based classifier. Moreover, the geometric features used here have been observed to be statistically significant, which enhance the statistical learning potential and classification accuracy of the classifier. Automated classification of SECT cells characterizes this precancerous condition very precisely in a quantitative manner and unveils the opportunity to understand OSF related changes in cell population having definite geometric properties. The paper presents an automated classification method for understanding the deviation of normal structural profile of oral mucosa during precancerous changes.