p53, Cytokeratin 19 Expression in Oral Squamous Cell Carcinoma and Correlation with Histopathologic Grading: An Immunohistochemical Study.

The purpose of this study was to examine the immunohistochemical expression of p53 and cytokeratin 19 (CK19) in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) and their association with histopathological differentiation grade. The secondary goal was to see if there was any correlation between p53 and CK19 expression in NOM and OSCC. A hospital-based retrospective analysis was conducted in which 40 NOM and 45 OSCC samples were acquired from archives and stained with mouse monoclonal antibodies p53 and CK19. For both the NOM and OSCC groups, the proportion of positively stained cells, staining intensity, and staining index were calculated. p53 immunoexpression revealed that 85% of positively stained cells in the NOM basal layer had a low staining index (mean ± SD 1.87 ± 0.34), whereas 66.7% of positively stained cells in the OSCC had a high staining index (mean ± SD 5.63 ± 3.02). When NOM and OSCC were compared, there was a statistically significant difference in staining intensity. However, despite a linear increase in the percentage of positive cells from well to poorly differentiated, the comparison between histopathological grades was non-significant. CK19 exhibited 18.5% positively stained cells in the NOM basal layer with a low staining index (mean ± SD 1.57 ± 0.53), whereas OSCC samples showed 4.44% immunopositivity with a high staining index. p53 is a marker of oral carcinogenesis independent of histological grade and CK19 expression. Further, CK19 is a marker of dysfunctional epithelial differentiation but lacks sensitivity and specificity; however, it demands further multicentric studies with a large sample size to draw definitive conclusions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04092-7.

Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis / Leucoplasia verrugosa proliferativa/leucoplasia multifocalen pacientes con y sin fibrosis submucosa oral

Background: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oralpotentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinicalpractice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF tooutline the clinical behavior and challenges in the management of this high-risk group in clinical practice.Material and Methods: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over aperiod of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, med-ical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits,the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or whensurgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twicedaily was initiated.Results: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesionswere either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional orsystemic metastasis. Despite thorough interventions, the patients died of, or with the disease.Conclusions: The occurrence of two or more oral potentially malignant disorders poses challenges in patient man-agement and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to as-sess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.(AU)

Impact of changing classification systems on prevalence and frequency distribution of odontogenic tumors in tertiary care center of Nagpur.

INTRODUCTION: The classification of odontogenic tumors has been revised from time to time in order to provide unified terminology. This reclassification had considerable impact on their prevalence and frequency distribution. OBJECTIVES: This study was aimed to emphasize impact of changing classification systems on prevalence and relative frequency of odontogenic tumors. The secondary objective was to analyze demographics of various histological types of odontogenic tumors in comparison to published literature. Review of Indian studies (1992-2020) elaborating frequency of odontogenic tumors is summarized in the end. METHODS: This was a hospital-based retrospective study wherein case files of odontogenic tumors diagnosed from 1990 to 2019 period were retrieved. The classification system used originally at the time of diagnosis was retained and prevalence of odontogenic tumors in three different periods (1990-2004, 2005-2016 and 2017-2019) was compared. Further, prevalence, frequency distribution and demographics of all these tumors (1990-2019) were analyzed using latest World Health Organization 2017 classification. RESULTS: A total of 345 odontogenic tumors was diagnosed as per World Health Organization 2017 system of classification from 1990 to 2019. 96.81% tumors were benign and 3.81% constituted malignant odontogenic tumors. However, there was marked increase in prevalence of odontogenic tumors in 2005-2016 (6.2%) period as compared to 1990-2004 (3.87%) and 2017-2019 (3.47%). Ameloblastoma remained the most common tumor in three different periods, whereas keratocystic odontogenic tumor became second commonest tumor in 2005-2016 as compared to odontoma in 1990-2004 and adenomatoid odontogenic tumor in 2017-2019. CONCLUSIONS: The continuous evolving systems of classification may partly be responsible for inconsistency in odontogenic tumors, with inclusion of keratocystic odontogenic tumor,and has marked impact on prevalence and frequency distribution of odontogenic tumors. The geographical variations in demographics of odontogenic tumors might reflect genetic and environment influence; however it requires elucidation by further studies.

Impact of changing classification systems on prevalence and frequency distribution of odontogenic tumors in tertiary care center of Nagpur / Impacto da mudança nos sistemas de classificação sobre a prevalência e a distribuição da frequência de tumores odontogênicos em um centro de atenção terciária de Nagpur

Abstract Introduction The classification of odontogenic tumors has been revised from time to time in order to provide unified terminology. This reclassification had considerable impact on their prevalence and frequency distribution. Objectives This study was aimed to emphasize impact of changing classification systems on prevalence and relative frequency of odontogenic tumors. The secondary objective was to analyze demographics of various histological types of odontogenic tumors in comparison to published literature. Review of Indian studies (1992-2020) elaborating frequency of odontogenic tumors is summarized in the end. Methods This was a hospital-based retrospective study wherein case files of odontogenic tumors diagnosed from 1990 to 2019 period were retrieved. The classification system used originally at the time of diagnosis was retained and prevalence of odontogenic tumors in three different periods (1990-2004, 2005-2016 and 2017-2019) was compared. Further, prevalence, frequency distribution and demographics of all these tumors (1990-2019) were analyzed using latest World Health Organization 2017 classification. Results A total of 345 odontogenic tumors was diagnosed as per World Health Organization 2017 system of classification from 1990 to 2019. 96.81% tumors were benign and 3.81% constituted malignant odontogenic tumors. However, there was marked increase in prevalence of odontogenic tumors in 2005-2016 (6.2%) period as compared to 1990-2004 (3.87%) and 2017-2019 (3.47%). Ameloblastoma remained the most common tumor in three different periods, whereas keratocystic odontogenic tumor became second commonest tumor in 2005-2016 as compared to odontoma in 1990-2004 and adenomatoid odontogenic tumor in 2017-2019. Conclusions The continuous evolving systems of classification may partly be responsible for inconsistency in odontogenic tumors, with inclusion of keratocystic odontogenic tumor,and has marked impact on prevalence and frequency distribution of odontogenic tumors. The geographical variations in demographics of odontogenic tumors might reflect genetic and environment influence; however it requires elucidation by further studies.

Resumo Introdução A classificação dos tumores odontogênicos é revisada de tempos em tempos para fornecer uma terminologia unificada. Essas revisões tiveram um impacto considerável na prevalência e distribuição da frequência desses tumores. Objetivo Enfatizar o impacto da mudança dos sistemas de classificação na prevalência e frequência relativa dos tumores odontogênicos. O objetivo secundário foi analisar os dados demográficos de vários tipos histológicos de tumores odontogênicos em comparação com a literatura publicada. A revisão dos estudos indianos (1992-2020) sobre a frequência dos tumores odontogênicos é resumida no fim. Método Este foi um estudo retrospectivo com base em registro hospitalar de casos de tumores odontogênicos diagnosticados de 1990‐2019 que foram revisados. O sistema de classificação usado originalmente no momento do diagnóstico foi mantido e a prevalência de tumores odontogênicos em três períodos (1990-2004, 2005-2016 e 2017-2019) foi comparada. Além disso, a prevalência, a distribuição da frequência e os dados demográficos de todos esses tumores (1990-2019) foram analisados com a classificação mais recente da OMS de 2017. Resultados Foram diagnosticados 345 tumores odontogênicos de acordo com o sistema de classificação da OMS (2017) de 1990-2019. A ocorrência de tumores odontogênicos benignos e malignos foi de 96,81% e 3,81%, respectivamente. Contudo, houve um aumento acentuado na prevalência de tumores odontogênicos de 2005‐2016 (6,2%), comparado aos períodos de 1990‐2004 (3,87%) e 2017‐2019 (3,47%). O ameloblastoma permaneceu como o tumor mais comum em três períodos, enquanto o tumor odontogênico ceratocístico passou a ser o segundo tumor mais comum em 2005‐2016, comparado ao odontoma em 1990‐2004 e ao tumor odontogênico adenomatoide em 2017‐2019. Conclusões Os sistemas de classificação em evolução contínua podem, em parte, atribuir uma inconsistência à classificação dos tumores odontogênicos com a inclusão do tumor odontogênico ceratocístico e causar um impacto marcante na prevalência e distribuição da frequência dos tumores odontogênicos. As variações geográficas na demografia dos tumores odontogênicos podem refletir influências genéticas e ambientais, mas requerem elucidação por estudos futuros.

Intra-observer and inter-observer variability in two grading systems for oral epithelial dysplasia: A multi-centre study in India.

BACKGROUND: The presence and grading of oral epithelial dysplasia (OED) are considered the gold standard for predicting the malignant risk of oral potentially malignant disorders. However, inter-observer and intra-observer agreement in the context of reporting on OED grading has been reputedly considered unreliable. METHODS: We undertook a multi-centre study of six Indian oral pathologists to assess variations in reporting OED using the World Health Organization (WHO; 2005) system and also the recently introduced binary system. The observer variability was assessed with the use of kappa statistics. RESULTS: The weighted kappa intra-observer agreement scores improved (κw  = 0.5012) on grouping by two grades as no and mild dysplasia versus moderate and severe dysplasia compared to binary grading system (κ = 0.1563) and WHO grading system (κw  = 0.4297). Poor to fair inter-observer agreement scores were seen between the principal investigator (PI) and the other five observers using the WHO grading system (κ = 0.051-0.231; κw  = 0.145 to 0.361; 35% to 46%) and binary grading system (κ = 0.049 to 0.326; 50 to 65%). CONCLUSIONS: There is considerable room for improvement in the assessment of OED using either system to help in standardised reporting. The professional pathology organisations in India should take steps to provide external quality assessment in reporting OED among oral and general pathologists who are engaged in routine reporting of head and neck specimens.

Matrix metalloproteinases-3 gene-promoter polymorphism as a risk factor in oral submucous fibrosis in an Indian population: a pilot study.

AIM: Host-related factors could be important to the fundamental understanding of oral diseases. One such factor is matrix metalloproteinases (MMP). MMP3 (stromelysin 1) is crucial in connective tissue remodeling. Promoter regions are specific segments of DNA that control the rate of mRNA synthesis. Thus, polymorphism in the (5A/6A) promoter region of the MMP3 gene results in different transcriptional activities and is related to susceptibility in diseases. The aim of the present study was to detect polymorphism in the MMP3 gene-promoter region in oral submucous fibrosis patients (OSF), oral squamous cell carcinoma patients (OSCC), and normal individuals with tobacco and areca nut habit and without lesions, and to correlate the genotype as a risk factor in these diseases. METHOD: Genomic DNA from blood of OSF (n = 5), OSCC (n = 5), and normal individuals with tobacco and areca nut habit (n = 5) and without (n = 5) were subjected to polymerase chain reaction of the MMP3 gene-promoter region and DNA sequencing. RESULTS: The 5A allele in the MMP3 gene-promoter region was observed more frequently in the OSF group than the control groups. No significant difference was noted between OSCC and the control groups on the 5A allele. CONCLUSION: The results indicated that the 5A allele of the MMP3 gene-promoter region could be associated with OSF risk factor, but not OSCC, in an Indian population.

Detection of Porphyromonas gingivalis and Treponema denticola in chronic and aggressive periodontitis patients: A comparative polymerase chain reaction study.

BACKGROUND: The detection frequency of Porphyromonas gingivalis and Treponema denticola in chronic periodontitis (CP) and aggressive periodontitis (AgP) is not explored well in Indian population. AIM: The study was undertaken to detect P. gingivalis and T. denticola in CP as well as in AgP patients using polymerase chain reaction (PCR), and to determine the relationship between the frequency of these two microorganisms and the severity of clinical periodontal parameters. MATERIALS AND METHODS: Subgingival plaque samples were collected from ninety participants (thirty CP patients, thirty AgP patients, and thirty healthy participants) and the aforementioned two microorganisms were detected using PCR. RESULTS: However, when CP and AgP were compared for the detection frequency of two microorganisms, no statistically significant difference was noted. A statistically significant increase in the number of bacteria-positive sites increased as the score of plaque index (PI), gingival index (GI), and clinical attachment level of CP and AgP patients increased. Coexistence of P. gingivalis and T. denticola was frequently observed in deep periodontal pockets. CONCLUSIONS: Study findings suggest that P. gingivalis and T. denticola are significantly associated with the severity of periodontal tissue destruction. Statistically significant association exists between clinical periodontal parameters such as PI, GI, periodontal pocket depth (PPD), and clinical attachment loss and presence of both the microorganisms.

Exophytic Verrucous Hyperplasia of the Oral Cavity ­ Application of Standardized Criteria for Diagnosis from a Consensus Report

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the 'First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity' held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named 'Exophytic Verrucous Hyperplasia'. Previously described clinical features of OVH such as the 'blunt' or 'sharp' variants; and the 'mass' or 'plaque' variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of 'Exophytic Verrucous Hyperplasia' as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

A randomized control trial measuring the effectiveness of a mouth-exercising device for mucosal burning in oral submucous fibrosis.

OBJECTIVES: To evaluate effect of ice-cream stick exercise regimen with or without a mouth-exercising device (MED) on mucosal burning sensation in oral submucous fibrosis. STUDY DESIGN: In total, 282 patients with oral submucous fibrosis were treated with topical corticosteroid and oral antioxidant and the ice-cream stick exercise regimen. Patients in subgroups A1, A2, and A3 were additionally given a new MED. Patients in subgroups A1 and B1 patients with interincisal distance (IID) of 20 to 35 mm were managed without any additional therapy; patients in subgroups A2 and B2 with IID of 20 to 35 mm were additionally managed with intralesional injections; and those in subgroups A3 and B3 with IID less than 20 mm were managed surgically. Subjective evaluation of decrease in the oral mucosal burning was measured on a visual analogue scale (VAS). Analysis of variance and Tukey's multiple post hoc analysis were carried out to present the results. RESULTS: Patients using the MED, that is, subgroups A1, A2, and A3, showed reduction in burning sensation in the range of 64.8% to 71.1% and 27.8% to 30.9%, whereas in subgroups B1, B2, and B3, reduction in burning sensation ranged from 64.7% to 69.9% and from 29.3% to 38.6% after 6 months. The wo-way analysis of variance indicated statistically significant results in changes in initial VAS scores to 6-monthly VAS scores between MED users and non-MED users. CONCLUSIONS: The MED helps to enhance the rate of reduction of mucosal burning sensation, in addition to the conventional ice-cream stick regimen, as an adjunct to local and surgical treatment.