Circulating Tumour Cell Biomarkers in Head and Neck Cancer: Current Progress and Future Prospects

Abstract

Head and neck cancer (HNC) continues to carry a significant burden of disease both for patients and health services. Facilitating biomarker-led treatment decisions is critical to improve outcomes in this group and deliver therapy tailored to the individual tumour biological profile. One solution to develop such biomarkers is a liquid biopsy analysing circulating tumour cells (CTCs)-providing a non-invasive and dynamic assessment of tumour specific alterations in 'real-time'. A major obstacle to implementing such a test is the standardisation of CTC isolation methods and subsequent down-stream analysis. Several options are available, with a recent shift in vogue from positive-selection marker-dependent isolation systems to marker-independent negative-selection techniques. HNC single-CTC characterisation, including single-cell sequencing, to identify actionable mutations and gene-expression signatures has the potential to both guide the understanding of patient tumour heterogeneity and support the adoption of personalised medicine strategies. Microfluidic approaches for isolating CTCs and cell clusters are emerging as novel technologies which can be incorporated with computational platforms to complement current diagnostic and prognostic strategies. We review the current literature to assess progress regarding CTC biomarkers in HNC and potential avenues for future translational research and clinical implementation.

Keywords: biomarker; circulating tumour cell; head and neck cancer.

Figure 1

Diagrammatic representation of the relationship between circulating tumour cell (CTC) isolation strategies, biomarker outputs and clinical applications.

Figure 2

An example of CTC enrichment using a microfluidic device: (a) the Parsortix™ (Angle Plc) system, (b) diagram of microfluidic flow and cell sorting within the isolation cassette, (c) Close-up of the isolation cassette demonstrating tiered multi-channel design, (d) head and neck squamous cell carcinoma cells (FaDu cell line) isolated from spiked blood sample using Parsortix™ and stained with pan-cytokeratin antibody (Parsortix™ enriches CTCs ≈ 1000-fold, however anti-CD45 staining is also required to negatively select the contaminating white blood cell population or deplete CD45+ve cells to provide a pure CTC population) at 20× magnification.