Liquid Biopsy in Head and Neck Cancer: Promises and Challenges

Abstract

Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Keywords: biomarker; circulating tumor DNA; circulating tumor cell; exosomal miRNA; saliva-exosomics; salivary diagnostics.

Figure 1.

Circulating biomarkers in head and neck cancer. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs are complementary biomarkers present in plasma and/or saliva. Apoptotic tumor cells release ctDNA into blood, whereas necrotic tumor cells shed ctDNA into saliva. Tumor cells release exosomal miRNAs into blood and saliva. Primary tumor and metastatic lesions release CTCs into blood.

Figure 2.

Potential clinical applications of circulating biomarkers in the treatment of head and neck cancer. (A) Schematic time course of disease management and tumor size in head and neck cancer patients undergoing chemotherapy (or immunotherapy) and surgery. Plasma circulating tumor DNA (ctDNA) analysis allows early detection, monitoring treatment response, monitoring minimal residual disease (MRD), and predicting metastasis. Circulating tumor cell (CTC) analysis can assist the selection of targeted therapies. Exosomal miRNAs currently offer limited insight into clinical applications. Salivary ctDNA analysis can provide complementary information. (B) Use of plasma and salivary ctDNA in combination allows higher detection of cancer than use of plasma ctDNA alone. A spike in ctDNA level reflects transient tumor cell death by systemic therapy.