Abstract
ABSTRACTPurposeThe human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response.Experimental DesignSixty-six patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care (SOC) treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma samples were collected at baseline, during weeks 1, 3, and 5 of chemoRT, and 3-4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy.ResultsThe median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared to SOC. HPV cfDNA clearance correlated with better 2-yr RFS (92.9% vs. 30%, log-rank p=0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index (CI) 0.83, which improved when combined with MRI response (CI 0.88).ConclusionsHPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at first follow-up predict RFS, and the therapeutic HPV vaccine was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.
Publisher
Cold Spring Harbor Laboratory