Clinical aspects of oral cancer and potentially malignant disorders in South and Southeast Asia.

BACKGROUND: Oral cancer and Oral Potentially Malignant Disorders (OPMD) are major health problems in South and Southeast Asia. AIMS: To describe and discuss the clinical aspects of Oral Cancer and OPMD in South and Southeast Asia. MATERIALS AND METHODS: Literature review of concepts and data over the last four decades. DISCUSSION: Asian countries account for about two-thirds of new cases of oral cancer (OC) globally, with the highest burden in the South and Southeast Asian countries, including Pakistan and India. Habits, dietary patterns, socioeconomic status, and access to routine dental care play a crucial role in defining the demographics and clinical presentation of OC in these regions and significantly influence the morbidity and mortality of the disease. This region sees the use of different types of tobacco with or without areca nut (AN), such as pan masala, gutka, gul, snuff, mawa, and mishri. Tobacco use is high among men in Sri Lanka, Myanmar, Maldives, Bangladesh, Nepal, India and Bhutan. Areca nut is the fourth most common addictive substance globally and is frequently used in South and Southeast Asian countries, including Southeast China, Hainan Island, India, Taiwan, and the Pacific Islands, and immigrants from these regions in Africa, Europe, and North America. The use of these products results in mucosal alterations with varied clinical presentation of Oral Potentially Malignant Disorders (OPMDs) and OC. We discuss here the different types of OPMD and OC, the diagnostic aids and their relevance in clinical practice, and factors that influence their prognosis.

Expression of CD44 in Head and Neck Squamous Cell Carcinoma-An In-Silico Study.

Introduction CD44, a multistructural and multifunctional transmembrane glycoprotein, is a promising cancer stem cell (CSC) marker that regulates the properties of CSCs, including self-renewal, tumor initiation, and metastasis, and confers resistance to chemotherapy and radiotherapy. The aim of the present study was to evaluate the gene and protein expression of CD44 and explore its prognostic value in head and neck squamous cell carcinoma (HNSCC). Methodology The present observational study employs computational tools for analysis. The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma dataset (520 primary HNSCC and 44 normal tissues) from the University of Alabama at Birmingham Cancer platform was used to study the association of CD44 mRNA transcript levels with various clinicopathological characteristics of HNSCC including age, gender, tumor grade, tumor stage, human papillomavirus (HPV) status, p53 mutation status, and overall survival. The CD44 protein expression in HNSCC and normal tissues was ascertained using the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium Head-and-Neck cancer dataset (108 primary HNSCC and 71 normal tissues). Results CD44 mRNA transcript and protein expression levels were significantly higher in HNSCC tissues than in normal tissues, and high CD44 expression was correlated with poor survival. CD44 was upregulated in Stage 1 and Grade 2 HNSCC compared with other stages and grades. Overexpression of CD44 was observed in HPV-negative and TP53-positive mutant status in HNSCC. Conclusion The pleiotropic roles of CD44 in tumorigenesis urge the need to explore its differential expression in HNSCC. The study concludes that CD44 can be a potential diagnostic and prognostic biomarker for HNSCC and offer new molecular targets for CD44-targeted therapy for cancer management.

Immunohistochemical biomarkers in oral submucous fibrosis: A scoping review.

INTRODUCTION: This scoping review was done to study the immunohistochemical biomarkers involved in the pathogenesis and malignant transformation of oral submucous fibrosis (OSF), in literature published from 2010 to 2021. METHOD: The protocol was adapted from the Joanna Briggs Institute Reviewer's Manual (2017), and reported according to the PRISMA guidelines for Scoping Reviews. RESULTS: Eighty-six studies included in this review reported 84 immunohistochemical (IHC) biomarkers in OSF: 10 epithelial markers, 28 connective tissue markers, 22 proliferative markers, and 24 other biomarkers that are transcription factors, cancer stem cell markers, cell signaling markers, proteins, and enzymes. The commonly reported IHC biomarkers were alpha-smooth muscle actin (α-SMA) and E-cadherin (seven articles each) followed by vascular endothelial growth factor (VEGF) and CD34 (six articles each), p53, p63, and Ki67 (five articles each). α-SMA, Ki67, CD105, and hTERT were significantly increased in oral squamous cell carcinoma arising in a background of OSF (OSCC-OSF) compared with OSF and normal subjects. CONCLUSION: The identified surrogate IHC biomarkers reported in OSF in this scoping review require validation with long-term prospective studies to facilitate early diagnosis, for use in risk assessment, and plan appropriate treatment for OSF in clinical practice. Open Science Framework ID: osf.io/epwra.

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.

Oral epithelial dysplasia: Classifications and clinical relevance in risk assessment of oral potentially malignant disorders.

After more than a decade, the World Health Organization (WHO) published the revised grading system for oral epithelial dysplasia in 2017. The revised classification has changes reflecting our evolution of understanding of the dysplastic process. Although the WHO 2017 three-tier grading system is the gold standard for histological diagnosis of oral potentially malignant disorders, it has certain limitations. Suggestions to overcome these limitations include the use of clinical determinants and molecular markers to supplement the grading system. It has also been suggested that a two-tier system may be more reproducible and clinically translatable for better management. These advances in the understanding of epithelial dysplasia are very important globally and for us in the Indian subcontinent, given the prevalence of habits (tobacco/areca nut) and burden of oral cancer in this part of the world. The following review traces the evolution of the grading system of dysplasia, its relevance and clinical utility.

Association among interleukin-6 gene polymorphisms, type 2 diabetes mellitus, and chronic periodontitis: a pilot study.

AIM: The purpose of this pilot study was to determine the association between single nucleotide polymorphisms (-174 G>C) in the interleukin-6 (IL-6) gene with chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM) in south Indian population. METHODS: Genomic DNA was obtained from the white blood cells of 30 patients with T2DM, 30 patients with CP, 30 patients with T2DM with CP, and 30 controls. DNA was amplified using polymerase chain reaction with specific primers flanking the locus -174 of the IL-6 gene and further genotyped using the restriction fragment length polymorphism method. The genotype distribution and allele frequencies between the study groups were determined using χ2 -test. The relative risk was estimated with a 95% confidence interval. RESULTS: The CP group (26.7%) displayed a greater percentage of GC genotype (P = 0.026) when compared to the control group (3.3%). A statistically-significant difference in the allele frequencies was found between the control and CP group with the C-allele frequency being greater (0.13) in the CP group than normal controls (0.02). CONCLUSION: The GC genotype was found to be the risk genotype and the C allele was found to be the risk allele for the development of CP.