Liquid Biopsies in Head and Neck Cancers: Recent Developments Across Biofluids, Analytes, and Molecular Features

Head and neck cancers (HNCs) are too often diagnosed at advanced stages when outcomes are poor. Additionally, robust tools for the early detection of recurrence remain elusive. These gaps drive interest in so-called liquid biopsy approaches for HNC detection, prognostication, and surveillance. Molecular heterogeneity presents challenges to liquid biopsy testing, but emerging approaches provide promising avenues toward clinical utility.

We review the latest developments in HNC liquid biopsies, provide perspectives on viral-associated and nonviral-associated cancers, and assess various biofluids, analytes, and molecular profiling approaches.

Liquid biopsy assays targeting viral DNA from peripheral blood plasma have established clinical performance, and utility studies are ongoing, serving as a blueprint for other emerging assays.

The use of multiple biofluid sources and analytes may improve detection sensitivity and clinical applicability. Standardization and harmonization of analysis methods will be critical for enhancing biomarker discovery and enabling reliable clinical implementation.