Circulating Cell-Free DNA-Based Methylation Pattern in Saliva for Early Diagnosis of Head and Neck Cancer

Simple Summary Liquid biopsy represents a promising alternative to standard-of-care tissue biopsies, outperforming the latter in several aspects: invasiveness, cost, spatial limitation to a single region, and time to result. The pursuit of knowledge regarding the detection and analysis of circulating tumor DNA, especially methylation profiling, represents a unique opportunity for real-time detection and monitoring of tumor properties. Despite advances, most head and neck cancer patients are still diagnosed at an advanced stage, resulting in a poor prognosis. This review aims to synthesize our current understanding of DNA methylation changes in squamous cell head and neck cancer as a potential disease biomarker and to identify gaps for further research. Head and neck cancer (HNC) remains one of the leading causes of mortality worldwide due to tumor diagnosis at a late stage, loco-regional aggression, and distant metastases. A standardized diagnostic procedure for HNC is a tissue biopsy that cannot faithfully portray the in-depth tumor dynamics. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for cancer detection and follow-up. A saliva-based liquid biopsy allows convenient, non-invasive, and painless collection of high volumes of this biofluid, with the possibility of repetitive sampling, all enabling real-time monitoring of the disease. No approved clinical test for HNC has yet been established. However, epigenetic changes in saliva circulating cell-free DNA (cfDNA) have the potential for a wide range of clinical applications. Therefore, the aim of this review is to present an overview of cfDNA-based methylation patterns in saliva for early detection of HNC, with particular attention to circulating tumor DNA (ctDNA). Due to advancements in isolation and detection technologies, as well as next- and third-generation sequencing, recent data suggest that salivary biomarkers may be successfully applied for early detection of HNC in the future, but large prospective clinical trials are still warranted.

Automated summary

Liquid biopsy is a promising alternative to tissue biopsies, offering real-time detection and monitoring of tumor properties. It has significant implications for the diagnosis and prognosis of advanced stage head and neck cancer patients.