Does circulating tumor DNA apply as a reliable biomarker for the diagnosis and prognosis of head and neck squamous cell carcinoma?

Oral cavity cancer is the most common type of head and neck cancer. There is no definitive standard diagnosis, prognosis, or treatment response biomarker panel based on simple, specific, non-invasive, and reliable methods for head and neck squamous cell carcinoma (HNSCC) patients. On the other hand, the frequent post-treatment biopsies make it challenging to discriminate residual disease or recurrent tumors following postoperative reparative and post-radiation changes. Saliva, blood plasma, and serum samples were commonly used to monitor HNSCC through liquid biopsies. Based on the evidence, the most prominent molecular-based fluid biomarker, such as circulating tumor DNA (ctDNA), has potential applications for early cancer diagnosis, screening, patient management, and surveillance. ctDNA showed genomic and epigenomic changes and the status of human papillomavirus (HPV) with the real-time monitoring of tumor status through cancer therapy. Due to the intra and inter-tumor heterogeneity of tumor cells like cancer stem cells (CSCs) and tumor microenvironment (TME) in HNSCC, the tiny tissue biopsy cannot reflect all genomic and transcriptomic abnormality. Most liquid biopsies are applied to detect circulating molecular biomarkers consisting of cell-free DNA (cfDNA), ctDNA, microRNA, mRNA, and exosome for monitoring tumor progression. Based on the results of previous studies, liquid biopsy can be applied for comprehensive multi-omic discovery by assessing the predictive value of ctDNA in both early and advanced cancers. Liquid biopsy can be used to evaluate molecular signature profiles in HNSCC patients, with great potential to help in early diagnosis, prognosis, surveillance, and treatment monitoring of tumors. These happen by designing longitudinal extensive cohort studies and the utility of organoid technology that promotes the context of personalized and precision cancer medicine.