microRNAs in oral cancer: Moving from bench to bed as next generation medicine.

Oral cancer is the thirteenth most common cancer in the world, with India contributing to 33% of the global burden. Lack of specific non-invasive markers, non-improvement in patient survival and tumor recurrence remain a major clinical challenge in oral cancer. Epigenetic regulation in the form of microRNAs (miRs) that act as tumor suppressor miRs or oncomiRs has gained significant momentum with the advancement in the field, suggesting the potential for clinical application of miRs in oral cancer. The current review of literature identified miR-21, miR-27a(-3p), miR-31, miR-93, miR-134, miR-146, miR-155, miR-196a, miR-196b, miR-211, miR-218, miR-222, miR-372 and miR-373 to be up-regulated and let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, miR-26a, miR-99a-5p, miR-137, miR-139-5p, miR-143-3p, miR-184 and miR-375 to be down-regulated in oral cancer. Mechanistic studies have uncovered several miRs that are deregulated at varying levels and in different stages of oral cancer progression, thus providing clinical utility in better diagnosis as well as usefulness in prognosis by identifying patients with poor prognosis or stratifying patients based on responsiveness to chemo- and radio-therapy. Lastly, exogenous modulation of miR expression using miRNA-based drugs in combination with first-line agents may be adopted as a new therapeutic modality to treat oral cancer. Knowledge of miRs and their involvement in key molecular processes, clinical association, responsiveness to therapy and clinical advancement may highlight additional avenues in order to improve patient morbidity and mortality. Furthermore, combinatorial approaches with miR-therapy may be efficacious in oral cancer.

High-Risk Human Papillomavirus in Oral Cancer: Clinical Implications.

Oral cancer is the eleventh most common cancer globally, with well-established major risk factors of tobacco, areca nut, alcohol, and high-risk human papillomavirus (HR-HPV) types 16 and 18. HR-HPV16/18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. HPV-associated oropharyngeal and oral cancers show better prognosis and response to therapy. However, the picture of HR-HPV16/18 and the clinical implications of oral cancers are not clear with the majority of reports combining oral cancer data with head and neck cancers. The current review compiles the global prevalence of HR-HPV16/18 in oral cancers, highlighting the unique clinical and molecular pathologic features, prognosis and therapeutic strategies in the prevention and management of HPV-positive oral cancers. The potential for the use of de-intensified therapy and prophylactic prevention in HPV-positive oral cancer patients is highlighted.

OMICS, Oral Cancer Molecular Landscapes, and Clinical Practice.

Molecular pathogenesis of oral cancers continues to be researched by omics systems science biotechnologies. Oral cancers rank as the 13th most common cancer globally. Notably, the burden of oral cancers from the Asian continent is 56.21%, with 26% of the burden contributed by India. Despite easy accessibility of the oral cavity and hence early detection of oral cancers, majority are diagnosed in advanced stages in the Asian countries. Innovation in oral cancer diagnostics, as well as theranostics for precision medicine, would aid their early diagnosis, prognosis, and treatment, not to mention discovery of novel molecular targets for drug development. This expert review offers an analysis of oral cancer biomarkers, including somatic mutations, deregulated expression, epigenetic regulation, and genomic variants associated with oral cancer. We also discuss the implications of the current and emerging oral cancer biomarkers with a view to clinical practice, global health, and make suggestions for the ways forward.

Multiple single nucleotide polymorphism analysis and association of specific genotypes in FHIT, SAMD4A, and ANKRD17 in Indian patients with oral cancer.

BACKGROUND: Oral cancer has a high incidence primarily because of tobacco chewing habits. However, a small proportion of habitués develop oral cancer, implying a role for genomic variants in its susceptibility. METHODS: Thirteen single nucleotide polymorphisms (SNPs) in an Indian cohort comprising patients with oral cancer (n = 500) and healthy controls (n = 500) were genotyped using allelic discrimination real-time polymerase chain reaction (PCR). RESULTS: Prevalence of SNPs rs11130760, rs1957358, rs2306058, rs4883543, rs12637722, rs1457115, rs2353292, rs709821, rs2194861, rs4789378, rs3827538, rs2667552, and rs2886093 was determined in the Indian cohort. A significant association of rs11130760 GG (odds ratio [OR] 1.41; 95% confidence interval [CI] 1.08-1.84) and rs1957358 TT (OR 1.44; 95% CI 1.10-1.90) indicated increased risk; whereas rs1957358 TC (OR 0.67; 95% CI 0.53-0.87) and rs2306058 CT (OR 0.72; 95% CI 0.56-0.93) reflected decreased risk. The SNP rs11130760 wild-type (WT) allele G indicated an increased risk for oral cancer (OR 1.38; 95% CI 1.09-1.73), whereas SNP allele T indicated a decreased risk (OR 0.73; 95% CI 0.58-0.92) for oral cancer. CONCLUSION: Our study identified SNPs with susceptibility to oral cancer in high-risk populations.

Clinical implications of epigenetic regulation in oral cancer.

Oral cancer is a high incidence cancer which is of major public health concern in India being the most common cancer in males and fifth most common cancer in females in India, contributing to 26% of the global oral cancer burden. The major risk factors of oral cancer are tobacco, alcohol and high risk Human Papilloma Virus type 16/18. However, only 3-12% of the high risk individuals with dysplasia develop oral cancer. Thus, individual genomic variants representing the genomic constitution and epigenetic alterations play a critical role in the development of oral cancer. Extensive epigenetic studies on the molecular lesions including oncogenes, tumor suppressor genes, genes associated with apoptosis, DNA damage repair have been reported. The current review highlights epigenetic regulation with a focus on molecular biomarkers and epidrug therapy in oral cancer. Epigenetic regulation by hypermethylation, histone modifications and specific microRNAs are often associated with early events and advanced stages in oral cancer, and thus indicate epidrug therapy for intervention. The presence of epigenetic marks in oral lesions, cancers and tumor associated mucosa emphasizes indications as biomarkers and epidrugs with therapeutic potential for better patient management.