In a study reported in the Journal of Clinical Oncology, Han et al found that persistent human papillomavirus (HPV) circulating tumor DNA (ctDNA) after chemoradiation was associated with poorer outcomes in patients with cervical cancer. Patients at high risk of poorer outcomes could also be identified with early detection of ctDNA.
Study Details
The study involved data from 70 evaluable patients with stage IB to IVA cervical cancer treated with chemoradiation between 2017 and 2022 at four Canadian centers. Patients underwent phlebotomy at baseline, end of chemoradiation, 4 to 6 weeks postchemoradiation, and 3 months postchemoradiation for assessment of HPV ctDNA levels. Plasma HPV genotype-specific DNA levels were measured using both digital polymerase chain reaction (dPCR) and a next-generation sequencing approach (HPV-seq). The primary outcome measure was 2-year progression-free survival.
Key Findings
Median follow-up was 2.2 years (range = 0.5–5.5 years).
Progression-free survival at 2 years was significantly worse among patients with detectable HPV ctDNA on dPCR at the end of chemoradiation (51% vs 77%, P = .03), 4 to 6 weeks postchemoradiation (15% vs 82%, P < .001), and 3 months postchemoradiation (24% vs 82%, P < .001) vs those without detectable HPV ctDNA.
HPV-seq produced results similar to dPCR; progression-free survival at 2 years was significantly worse among patients with detectable HPV ctDNA at the end of chemoradiation (53% vs 87%, P = .009), 4 to 6 weeks postchemoradiation (39% vs 79%, P < .001), and 3 months postchemoradiation (26% vs 85%, P < .001) vs those without detectable HPV ctDNA.
On multivariate analysis, detectable HPV ctDNA on dPCR and HPV-seq, respectively, remained independently associated with poorer progression-free survival with detection at the end of chemoradiation (hazard ratio [HR] = 2.44, P = .045; HR = 4.13, P = .010), 4 to 6 weeks postchemoradiation (HR = 6.79, P < .001; HR = 3.86, P = .002), and 3 months postchemoradiation (HR = 5.50, P < .001; HR = 7.78, P < .001).
The investigators concluded, “Persistent HPV ctDNA after chemoradiation is independently associated with inferior progression-free survival. HPV ctDNA testing can identify, as early as at the end of chemoradiation, patients at high risk of recurrence for future treatment intensification trials.”
Kathy Han, MD, MSc, of the Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Cancer Research Society, Princess Margaret Hospital Foundation, and Ontario Institute for Cancer Research. For full disclosures of the study authors, visit ascopubs.org.
