Grading Systems For Oral Epithelial Dysplasia Research Articles

Calibration improves the agreement in grading oral epithelial dysplasia-Findings from a National Workshop in Malaysia.

A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems. A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems. A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise. This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.

Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems Versus S100A7 Immunohistochemical Signature-based Grading.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

Grading systems of oral cavity pre-malignancy: a systematic review and meta-analysis.

Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18-15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386-0.723) and 12.7% (95% CI - 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640-0.740) and 0.388 (95% CI 0.195-0.552), respectively. Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guidemanagement (watchful waiting vs. excision) of these OPMDs.

GLUT-1 Expression: An Aid in Complementing the WHO Oral Epithelial Dysplasia Grading System

The clinicopathologic parameters alone are not sufficient to precisely predict if oral potentially malignant disorders (OPMDs) remain unchanged, i.e., without any malignant changes, regress, or advance to oral squamous cell carcinomas (OSCC). Few of the OPMDs, with or without epithelial dysplasia, may transform to frank OSCC. Discovering various molecular markers that can predict OSCC transformation is essential to develop effective therapeutic strategies. GLUT-1 is one of the hypoxia as well as metabolic indicator markers that have been used to study the metabolic activity of the cells. Hence, given by the World Health Organization (WHO), GLUT-1 expression was studied in various grades of dysplasia to see whether it complements the WHO grading system (mild, moderate, and severe). The study was carried out on paraffin-embedded tissues of 10 normal oral mucosa and 30 OPMD cases. OPMD cases were classified into hyperkeratosis, mild dysplasia, moderate dysplasia, and severe dysplasia groups. Immunohistochemistry was carried out to evaluate the expression of GLUT-1 antigen. According to the WHO grading system of dysplasia, 11 (36.66%) cases were classified as hyperkeratosis, 9 (30%) cases were classified as mild dysplasia, 6 (20%) cases as moderate dysplasia, and 4 (13.33%) cases as severe dysplasia. There was a significant increase in GLUT-1 expression from normal to mild, moderate, and severe dysplasia (p value = 0.00). The expression of GLUT-1 marker complements the WHO grading system of oral epithelial dysplasia. GLUT-1 expression can be used to complement the WHO grading system to grade epithelial dysplasia.

Inter-examiner variability in grading oral epithelial dysplasia may result in suboptimal management of oral potentially malignant disorders

Oral epithelial dysplasia (OED) grading determines the management guidelines for oral potentially malignant disorders (OPMDs). The subjectivity of OED grading considerably impacts its reliability. Objective: This study aimed to assess the reproducibility of and variability in diagnosing and grading OED by oral and medical pathologists, using the conventional WHO 2005 classification. Material & methods: Five oral pathologists and one medical pathologist individually examined 200 hematoxylin and eosin-stained histological slides diagnosed as OED from oral pathology archives at the University of Peradeniya. The most experienced examiner’s diagnoses represented the standard for evaluating inter-examiner variability using the unweighted Cohen’s kappa coefficient. Results: OED grading among all oral pathologists revealed moderate agreement (kappa value, 0.42–0.50), whereas the medical pathologist showed poor agreement (kappa value, 0.034). The accepted OED diagnoses were mild, 33%; moderate, 24.9%; severe, 32.4%; and no dysplasia, 9.7%. However, 86.5% of the diagnoses by the medical pathologist were mild-no dysplasia. Diagnoses of moderate and severe dysplasia had lesser reproducibility than those of no dysplasia. Conclusions: OED grading was only moderately reproducible among oral pathologists and poorly reproducible with regard to the medical pathologist. A more reliable OED grading system is required to improve reproducibility for optimal OPMD management and assessment.

PROGNOSTIC CLASSIfiER FOR ORAL POTENTIALLY MALIGNANT DISORDERS: AN INTEGRATED HISTOPATHOLOGICAL AND MOLECULAR APPROACH

Objectives Oral squamous cell carcinoma (OSCC) is associated with a high degree of morbidity and mortality. OS-CCs are often preceded by oral potentially malignant disorders (OPMD) which have a higher propensity to undergo malignant transformation (MT) compared to clinically normal oral mucosa. Currently there is no reliable method to determine which OPMD cases will undergo MT. This study was performed to construct a prognostic classifier for patients with OPMD by integrating clinical, histopathological and molecular factors and to discover a gene expression signature that characterises OPMD with a high risk of undergoing MT. Findings Statistical analysis of an OPMD patient cohort (23 MT vs. 25 with no MT) showed that site of initial OPMD (p = 0.043), binary oral epithelial dysplasia (OED) grading (p = 0.009) and loss of heterozygosity at 3p/9p/17p (p = 0.026) were statistically significant. Other demographic factors, clinical features and the WHO 3-tiered OED grading system were not statistically significant. Gene expression experiments revealed several genes that were differentially expressed between OPMD that underwent MT and those that did not [false discovery rate of Conclusions Our findings show that a classifier combining histopathological and molecular factors outperforms conventional methods for prognosticating clinical outcome in patients with OPMD. We have also shown that formalin-fixed paraffin-embedded tissue can be used to generate a molecular classification with clinical utility.

Ki67, CD105, and α-SMA expressions better relate the binary oral epithelial dysplasia grading system of World Health Organization.

The binary system of oral epithelial dysplasia (OED) has never been investigated with reference to the carcinogenesis-related biomarkers. Hence, Ki67, CD105, and α-SMA immune-expressions were studied in oral potentially malignant disorders (OPMDs) to assess their relationship with the binary OED grading system of World Health Organization. The study was carried out on paraffin-embedded tissues of 30 normal oral mucosa (NOM) and 140 OPMD cases. OPMD cases were classified into two groups "no/questionable/hyperkeratosis/mild"=low-risk epithelial dysplasia (LRED) and "moderate or severe"=high-risk epithelial dysplasia (HRED). The immunohistochemistry was carried out to evaluate the expression of Ki67, CD 105, and α-SMA antigen. According to the binary grading system of WHO, 69 (49.28%) cases were LRED, while 71 (50.71%) case showed HRED. There was significant increase in Ki67 labeling index (LI) from NOM to LRED to HRED (P=.000). Similarly, mean vascular density (MVD) also increased significantly from NOM to LRED to HRED (P=.000). The α-SMA expression was significantly higher in HERD compared to LRED and NOM (P=.000). A positive correlation was noted among Ki67 LI, MVD, and α-SMA expressions in NOM, LRED, and HRED (P=.000). The expressions of ki67, CD105, and α-SMA markers compliment binary grading system of OED in OPMDS, thus justifying its use in clinical practice.

Inter- and intra-observer variability in three grading systems for oral epithelial dysplasia.

Background and Objectives:Management of oral premalignant lesions depends on clinical assessment and grading of oral epithelial dysplasia (OED), which remains one of the most important predictors of malignant potential. Numerous grading systems for OED exists with varying sets of assessing criteria and are largely considered subjective. The present study attempted to assess the inter- and intra-observer variability in three grading systems: Binary system, WHO (2005) and Ljubljana systems.Methodology:Histopathological grading of 63 cases of leukoplakia was performed by two oral pathologists and one general pathologist, who were blinded, using all the three grading systems at different time intervals and was repeated twice. Inter- and intra-observer variability was then evaluated by multivariate kappa analysis.Results:Inter-observer agreement in the two set of observations was found to be “slight” in WHO (k = 0.001 and 0.039), “slight” and “poor” in binary (k = 0.108 and −0.007), “poor” and “slight” in Ljubljana's (k = −0.027 and 0.106) grading systems. Intra-observer agreement ranged from “slight” to “fair” (k = 0.128 and 0.295) in WHO, “fair” to “moderate” (k = 0.224 and 0.420) in binary and “slight” to “fair” (k = 0.161 and −0.353) in Ljubljana's grading systems.Conclusions:The binary system of classification proved to have an overall better inter- and intra-observer agreement. This study also showed better intra-observer agreement in all the grading systems as well as in individual histopathological parameters. Defining the individual parameters more objectively with the reproducible structuring of the grading systems and training of the pathologists would help reduce the variability in diagnosing dysplasia.

Malignant transformation of oral epithelial dysplasia: a real-world evaluation of histopathologic grading

This study describes the predictive value of oral epithelial dysplasia (OED) grading as an indicator for malignant transformation and progression. The records of an Australian-based pathology laboratory were searched for oral mucosal biopsies with a dysplastic or malignant diagnosis. Examination for an association with progression and malignant transformation without reinterpretation was performed. Analysis was undertaken using hazard ratios and the Fisher exact test. A total of 368 patients with a diagnosis of OED were included. Twenty-six patients (7.1%) underwent progression or malignant transformation; the annual malignant transformation rate was 1%. No other characteristics were associated with a heightened risk of progression or transformation. The severity of OED was not associated with risk of malignant transformation, suggesting that the current OED grading system is not useful for predicting patient outcomes or for determining management strategies. Definitive treatment of all OED is recommended, until a more reliable progression/transformation system is developed.