Epigenetic Abnormalities and Head and Neck Cancer

Abstract

Staging and pathological grading systems are useful, but imperfect systems for predicting recurrence in patients with HNSCC. Molecular classification of HNSCCs is required to obtain prognostic as well as mechanistic information to improve patient care and outcomes. When normal cells are exposed to environmental carcinogens (e.g., chemical carcinogens and oncogenic viruses), DNA methyltransferase (DNMT) catalyzes enhances DNA methylation. Elevated levels of 5mC at tumor suppressor gene (TSG) promoters lead to TSG silencing and functional inactivation, ultimately contributing to tumor initiation or progression. Loss of TET (Ten-eleven translocation) activation through promoter methylation occurs in tumor cells, successively increasing the 5mC levels and promoting TSG inactivation. Enzymes of the TET family catalyze stepwise oxidation of 5mC in DNA to 5hmC and further oxidation products, not only generating new epigenetic markers but also triggering active or passive demethylation pathways.

HPV-related oropharyngeal carcinomas belong to an independent tumor type with regard to the cellular, biological, and clinical features. The HPV status, smoking status, tumor stage, and lymph node status are important factors that can be used to classify patients with low-, intermediate-, and high-risk of death. However, the optimal classification for patients with low-, intermediate-, and high-risk disease remains to be determined. Our findings support the use of methylation markers in patient selection for adjuvant therapy following primary treatment by surgery and oropharyngeal cancer surveillance programs.

Recently, the potential usefulness of cfDNA as a biomarker was shown. Liquid biopsy utilizing tumor DNA in the circulating blood could address many limitations of tissue biopsies, while also opening up innovative paradigms in cancer care. Analyses using DNA methylation-based strategies for detection of cfDNA have suggested that such approaches may pave the way for new advances for early cancer diagnosis.