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HPV circulating tumour DNA to guide cervical cancer therapy

Because cervical tumours carry viral DNA that normal cells do not, a blood test for HPV DNA is a near-perfect tumour marker for tracking response and relapse.

Plasma HPV ctDNA (droplet digital PCR or NGS) is detectable in most locally advanced cases, falls with chemoradiation, and predicts relapse months before imaging (Cabel, Han, and others). Analogous to HPV ctDNA in oropharyngeal cancer, where commercial assays exist.

Hypothesis
Persistent HPV ctDNA at the end of chemoradiation identifies patients who benefit from adjuvant immunotherapy, and undetectable ctDNA allows omission of pembrolizumab maintenance.
Rationale
Tumour-specific analyte with essentially zero background; cheap PCR; would make KEYNOTE-A18's benefit affordable by targeting it.
What would test it
Prospective ctDNA-stratified randomisation of maintenance pembrolizumab after chemoradiation; primary endpoint PFS.
Maturity
early clinical

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