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.

Keywords: IL-1β; lymphangiogenesis; microRNA; microbiota; mitochondrion; oral squamous cell carcinoma; tumor microenvironment.

Figure 1

Major factors involving the formation of oral cancer. New insights into preventive, diagnostic and therapeutic strategies for oral cancer may be derived through integrative investigations on these factors.

Figure 2

Schematic representation of IL-1β and mitochondrial Lon’s regulation of an immunosuppressive TME. Red arrow indicates overexpression; black arrow indicates activation or promotion. Abbreviations: CCL22 = C-C motif chemokine ligand 22, CCR4 = C-C chemokine receptor type 4, IRF3/7 = IFN regulatory factor-3 and 7, ROS = reactive oxygen species, mtDNA = mitochondrial DNA.