The American Head and Neck Society has reviewed the state of circulating tumour DNA in head and neck cancer, covering both tumour-derived DNA and oncogenic viral DNA, and surveying the trials now running.
The strongest case is in the virus-associated cancers, where the target is clean: HPV DNA in oropharyngeal cancer and Epstein-Barr virus DNA in nasopharyngeal cancer. In those settings, a liquid biopsy has a defined sequence to look for rather than a patient-specific mutation panel to build, which is why it has moved fastest there. The review sets out the proposed uses - diagnosis, surveillance, monitoring treatment response, and detecting minimal residual disease to adapt treatment.
It also states the problems plainly, and these are the part to carry away. Assays vary between laboratories, and the consequences of an inaccurate result are asymmetric: a false positive sends a patient who is well into imaging and anxiety, while a false negative offers reassurance that is not earned. Trial designs to answer whether acting on ctDNA improves outcomes are still being optimised, which is a careful way of saying no one has shown that it does. For a surgeon in India, where Epstein-Barr virus-associated nasopharyngeal cancer is concentrated in the north-east and HPV-associated oropharyngeal disease is rising, the practical position is that this is a test to follow rather than to order - and that a commercially offered liquid biopsy is not yet a surveillance strategy.
- Do not substitute circulating tumour DNA for clinical and imaging surveillance - no trial has shown that acting on it improves outcomes
- Where a patient has had a commercial liquid biopsy done elsewhere, interpret a positive result cautiously and do not start treatment on it alone
- Note the distinction that matters: viral DNA in HPV and Epstein-Barr virus-associated cancers is a cleaner target than tumour-specific ctDNA
- Ask which assay was used and at which laboratory - between-assay variability is one of the review's central concerns
- Consider trial enrolment where available rather than off-protocol use
Why it matters
It names the gap between a biomarker being detectable and a biomarker being usable, at the point where commercial tests are already being sold.
Don't overread it
This is a narrative review of an evolving field, not an evidence synthesis with pooled performance figures.
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