Genetic Alterations and Microbial Dysbiosis Underlie Lymph Node Metastasis in Tongue Cancer

Oral cancer presents a significant clinical challenge due to the presence of hidden lymph node metastases, which greatly influence treatment decisions. Advances in detection techniques, novel therapeutic regimens, and patient classification are being developed based on our understanding of the genetic and molecular factors associated with metastasis. Furthermore, the microbial community within the oral cavity plays a crucial role in tumor development and metastasis. Human papillomavirus (HPV) is a major risk factor for head and neck cancers, particularly oropharyngeal cancer, and its prevalence impacts the landscape of genetic alteration. The process of nodal metastasis formation in oral cancer is influenced by a combination of external and internal elements. Molecular profiling has revealed distinctive features of nodal metastases, including abnormalities in genes associated with the non-homologous end-joining (NHEJ) and homologous recombination (HR) pathways, hotspot mutations in genes such as TP53 and CASP8, and the potential utility of MMP10 as a biomarker. Additionally, microbial signatures, such as the 30-feature bacterial signature in oral cancer and miRNA signatures related to Fusobacterium nucleatum in tongue cancer, hold promise for patient classification. However, comprehensive evaluation of these genetic and pathogenic components in a large sample cohort is necessary to translate these findings into therapeutic decision-making. Early and accurate detection of nodal metastasis would enable appropriate lymph node removal and improve clinical prognosis. A comprehensive understanding of these characteristics and their association with the biology of oral cancer may also unveil therapeutic opportunities for patients lacking access to FDA-approved targeted medications.