New Insights Into Oral Squamous Cell Carcinoma: From Clinical Aspects to Molecular Tumorigenesis

Abstract

Oral squamous cell carcinoma (SCC) is a prevalent malignant disease worldwide, especially so in Taiwan. Early- or even preclinical-stage detection is critical for reducing morbidity and mortality from oral SCC. Epidemiological and genome association studies are useful for identifying clinicopathological risk factors for preventive, diagnostic, and therapeutic approaches of oral SCC. For advanced oral SCC, effective treatments are critical to prolonging survival and enhancing quality of life. As oral SCC is characteristic of regional invasion with lymph node metastases, understanding the aggressive features of oral SCC, particularly in lymphangiogenesis, is essential for determining effective treatments. Emerging evidence has demonstrated that the tumor microenvironment (TME) plays a pivotal role in tumor growth, invasion, and metastases. Recent clinical successes in immune checkpoint inhibitors either alone or combined with chemotherapy have also supported the therapeutic value of immunotherapy in oral SCC. This review summarizes critical advances in basic knowledge of oral SCC from the perspective of clinicopathological risk factors, molecular tumorigenesis, and the TME. We also highlight our recent investigations on the microbiome, genome association studies, lymphangiogenesis, and immunomodulation in oral SCC. This review may provide new insights for oral SCC treatment by systematically interpreting emerging evidence from various preclinical and clinical studies.

The Impact of m1A Methylation Modification Patterns on Tumor Immune Microenvironment and Prognosis in Oral Squamous Cell Carcinoma

“…It is generally accepted that upregulation of immune-checkpoint molecules can be induced by tumors, leading to a prominent immune evasion mechanism [ 47 ]. CTLA-4 , PD-1 , PD-L1 , LAG3 , TIGIT , and GITR have been reported as immunosuppressive molecules that help in maintaining the host tolerance by attenuating T cell functions [ 48 ]. Our study verified that the expression of CTLA-4 , PD-1 , and TIGIT is positively associated with m1A regulator expression, immune infiltration, and ssGSEA scores in m1A modification patterns, m1A gene clusters, and m1A score clusters.…”

m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Cell-Infiltration Characterization in Head and Neck Cancer

“…Recent studies suggest that PD-1/PD-L1 blockade immunotherapy exhibited more satisfactory curative effects with fewer undesirable adverse effects compared with traditional therapies for patients with head and neck cancer in advanced stages (Ferris et al, 2016;Seiwert et al, 2016;Addeo et al, 2019;Cohen et al, 2019). Mounting evidence has elucidated that besides tumor cells, the TME also plays a considerable role in tumor progression (Chen et al, 2021). TME is a complex composed of tumor cells and stromal cells including infiltrating immune cells (effector or regulatory T cells, M1/M2 macrophages, N1/N2 neutrophils, and natural killer cells), myeloid-derived suppressor cells (MDSCs), new blood vessels, and secreted factors such as cytokines and chemokines.…”

Advances in the Diagnosis, Monitoring, and Progression of Oral Cancer through Saliva: An Update

“…Tobacco use, alcohol consumption, and overinfection with some oncogenic papillomavirus (HPV) serotypes have been shown to be the main risk factors for developing oral cancer. In addition, other factors such as sun exposure and chronic mucosal irritation are also considered factors that may increase the risk of developing oral cancer [ 2 ]. Moreover, diet has also been suggested as a protective or risk factor for oral cancer according to Rodríguez-Molinero et al [ 3 ].…”