{"entity":{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","aka":[],"tldr":"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.","summary":"Cervical tumours carry HPV DNA that normal cells do not, so a blood test for HPV ctDNA is a near-perfect tumour marker, and this idea would use it to steer therapy. Plasma HPV ctDNA measured by droplet digital PCR or sequencing is detectable in most locally advanced cases, falls during chemoradiation, and predicts relapse months before imaging, as shown by Cabel, Han and others. The hypothesis is that persistent HPV ctDNA at the end of chemoradiation identifies the patients who benefit from adjuvant pembrolizumab, while undetectable ctDNA allows maintenance to be omitted. The rationale is a tumour-specific analyte with zero background measured by cheap PCR, which would make the KEYNOTE-A18 benefit affordable; the test is a ctDNA-stratified randomised trial, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04221945: KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","url":"https://clinicaltrials.gov/study/NCT04221945"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":["keynote-a18"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-a18-os-lancet-2024","paper-keynote-a18-pfs-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"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.","test":"Prospective ctDNA-stratified randomisation of maintenance pembrolizumab after chemoradiation; primary endpoint PFS.","maturity":"early-clinical"},"route":"/ideas/idea-hpv-ctdna-cervical/","neighbours":{"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"early-cervical-cancer","kind":"cancer","name":"Early cervical cancer and fertility-sparing surgery","route":"/cancers/early-cervical-cancer/"},{"id":"locally-advanced-cervical-cancer","kind":"cancer","name":"Locally advanced cervical cancer","route":"/cancers/locally-advanced-cervical-cancer/"},{"id":"recurrent-metastatic-cervical-cancer","kind":"cancer","name":"Recurrent or metastatic cervical cancer","route":"/cancers/recurrent-metastatic-cervical-cancer/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"keynote-a18","kind":"trial","name":"KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","route":"/trials/keynote-a18/"}],"paper":[{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","route":"/key-papers/paper-keynote-a18-os-lancet-2024/"},{"id":"paper-keynote-a18-pfs-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)","route":"/key-papers/paper-keynote-a18-pfs-lancet-2024/"}]}}