Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies

Abstract

The 5-year relative survival for patients with head and neck cancer, the seventh most common form of cancer worldwide, was reported as 67% in developed countries in the second decade of the new millennium. Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Recently, liquid biopsy monitoring of the molecular fingerprint of head and neck squamous cell carcinoma has been proposed and investigated as a strategy for longitudinal patient care. These innovative methods offer rapid, safe, and highly informative genetic analysis that can identify small tumors not yet visible by advanced imaging techniques, thus potentially shortening the time to treatment and improving survival outcomes. In this review, we provide insights into the available evidence that the molecular tumor fingerprint can be used in the surveillance of head and neck squamous cell carcinoma. Challenges to overcome, prior to clinical implementation, are also discussed.

Keywords: head and neck squamous cell carcinoma; liquid biopsy; minimal residual disease; relapse; surveillance.

Figure 1

Liquid biopsy profile versus imaging/clinical surveillance. Hypothetical patient surveillance curves using one or several liquid biopsy markers as discussed (black line). Dotted lines indicate the threshold levels which would allow imaging/clinical or liquid biopsy-based surveillance to trigger the suspicion of recurrence. Indicated is the hypothetical time gained using liquid biopsy-based surveillance, allowing faster clinical interventions.

Figure 2

Liquid biopsy surveillance strategies for head and neck squamous cell carcinoma (HNSCC). Summary of liquid biopsy-based surveillance strategies as discussed throughout this review. Although several choices are indicated (i.e., viral- or non-viral-driven tumors), it should be noted that a combination of strategies/surveillance options would probably offer the optimal path forward. RNA-based options are scarcely represented in the literature but are indicated as an option in this diagram.