{
    "abstract": "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.\nA total of 66 patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3 to 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.\nThe 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 with those who received standard-of-care therapy. HPV cfDNA clearance correlated with better 2-year 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 score of 0.83, which improved when combined with MRI response (concordance index, 0.88).\nHPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at follow-up predict RFS, and delivery of therapeutic HPV vaccine with chemoRT was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.",
    "authors": [
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Aaron",
            "initials": "A",
            "lastname": "Seo"
        },
        {
            "affiliation": "Thoracic/Head and Neck Medical Oncology Department, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Weihong",
            "initials": "W",
            "lastname": "Xiao"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Olsi",
            "initials": "O",
            "lastname": "Gjyshi"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Kyoko",
            "initials": "K",
            "lastname": "Yoshida-Court"
        },
        {
            "affiliation": "Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Peng",
            "initials": "P",
            "lastname": "Wei"
        },
        {
            "affiliation": "Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "David",
            "initials": "D",
            "lastname": "Swanson"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Tatiana",
            "initials": "T",
            "lastname": "Cisneros Napravnik"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Adam",
            "initials": "A",
            "lastname": "Grippin"
        },
        {
            "affiliation": "Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Aradhana M",
            "initials": "AM",
            "lastname": "Venkatesan"
        },
        {
            "affiliation": "Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Megan C",
            "initials": "MC",
            "lastname": "Jacobsen"
        },
        {
            "affiliation": "Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "David T",
            "initials": "DT",
            "lastname": "Fuentes"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Erica",
            "initials": "E",
            "lastname": "Lynn"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Julie",
            "initials": "J",
            "lastname": "Sammouri"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Anuja",
            "initials": "A",
            "lastname": "Jhingran"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Melissa",
            "initials": "M",
            "lastname": "Joyner"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Lilie L",
            "initials": "LL",
            "lastname": "Lin"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Lauren E",
            "initials": "LE",
            "lastname": "Colbert"
        },
        {
            "affiliation": null,
            "firstname": "Maura L",
            "initials": "ML",
            "lastname": "Gillison"
        },
        {
            "affiliation": "Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.",
            "firstname": "Ann H",
            "initials": "AH",
            "lastname": "Klopp"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a92024 American Association for Cancer Research.",
    "doi": "10.1158/1078-0432.CCR-24-2343",
    "journal": "Clinical cancer research : an official journal of the American Association for Cancer Research",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-12-16",
    "pubmed_id": "39680029",
    "results": "The 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 with those who received standard-of-care therapy. HPV cfDNA clearance correlated with better 2-year 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 score of 0.83, which improved when combined with MRI response (concordance index, 0.88).",
    "title": "Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Patients with Cervical Cancer Undergoing Definitive Chemoradiation.",
    "xml": "<Element 'PubmedArticle' at 0x7885046b69d0>"
}