DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a term collectively used to describe all cancers that develop in the oral and nasal cavities, the paranasal sinuses, the salivary glands, the pharynx, and the larynx. The majority (75%) of all newly diagnosed cases are observed in patients with locally advanced and aggressive disease, associated with significant relapse rates (30%) and poor prognostic outcomes, despite advances in multimodal treatment. Consequently, there is an unmet need for the identification and application of tools that would enable diagnosis at the earliest possible stage, accurately predict prognostic outcomes, contribute to the timely detection of relapses, and aid in the decision for therapy selection. Recent evidence suggests that DNA methylation can alter the expression of genes in a way that it favors tumorigenesis and tumor progression in HNSCC, and therefore represents a potential source for biomarker identification. This study summarizes the current knowledge on how abnormally methylated DNA profiles in HNSCC patients may contribute to the pathogenesis of HNSCC and designate the methylation patterns that have the potential to constitute clinically valuable biomarkers for achieving significant advances in the management of the disease and for improving survival outcomes in these patients.

Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer

“…Known contributors to OPSCC such as tobacco, alcohol abuse, and HPV positivity confer increased risk through epigenetic changes such as DNA methylation [176][177][178]. DNA methylation occurs through the addition of a methyl group to a carbon of cytosine, forming 5-methylcytosine [177]. This change in DNA structure leads to a change in the activity of transcription factors and the mobility of various proteins [179].…”

SP1 Gene Methylation in Head and Neck Squamous Cell Cancer in HPV-Negative Patients

“…In cases where DNA methylation is concentrated in the promoter region, it usually results in gene silencing. In contrast, when DNA methylation affects the core region of a gene, the result is usually an increase in gene expression [ 10 ]. To date, an increasing number of researchers tend to believe that malignant transformation of cells is preceded by a “breakdown” of the cell genome, consisting in the suppression of a tumor suppressor gene and/or activation of a pro-oncogene, to which epigenetic changes may lead.…”

Diagnóstico de câncer oral através de biomarcadores, uma proposta não invasiva

“…No Brasil, a ocorrência de casos é maior quando comparados com outros países, na estimativa realizada a cada treino (2020)(2021)(2022) O tipo mais comum de malignidade da cavidade oral é o carcinoma epidermóide (CEB), representando 90%. Este câncer pode atingir várias estruturas anatômicas, como língua, lábios, gengivas, superfície abaixo da língua, seios paranasais, glândulas salivares, faringe e laringe e entre outros, com grande potencial de malignidade (Liouta et al, 2023) Para realizar o diagnóstico desse câncer normalmente utilizam exame clínico completo da cavidade oral, na presença de lesão é realizada uma biópsia. Entretanto, o exame oral convencional não identifica alterações iniciais, o que impede o diagnóstico precoce.…”