Seo Aaron, Xiao Weihong, Gjyshi Olsi, Yoshida-Court Kyoko, Wei Peng, Swanson David, Cisneros Napravnik Tatiana, Grippin Adam, Venkatesan Aradhana M, Jacobsen Megan C, Fuentes David T, Lynn Erica, Sammouri Julie, Jhingran Anuja, Joyner Melissa, Lin Lilie L, Colbert Lauren E, Gillison Maura L, Klopp Ann H
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Thoracic/Head and Neck Medical Oncology Department, University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2025 Feb 17;31(4):697-706. doi: 10.1158/1078-0432.CCR-24-2343.
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.
A 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.
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).
HPV 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.
人乳头瘤病毒（HPV）是宫颈癌的一个重要病因。我们推测，在放化疗（chemoRT）之前、期间和之后检测病毒游离HPV DNA（cfDNA），可以深入了解疾病范围、临床分期和治疗反应。
2017年至2023年期间，共招募了66例局部晚期宫颈癌患者，其中49例接受标准治疗，17例参与一项联合治疗性HPV疫苗（PDS0101；IMMUNOCERV）的临床试验。在基线、chemoRT的第1、3和5周以及chemoRT后3至4个月采集血浆。使用针对13种高危型HPV E6/E7癌基因的液滴数字PCR对HPV cfDNA进行定量。在基线和近距离放疗前进行MRI检查。
中位随访时间为23个月，2年无复发生存率（RFS）为78.4%。基线时淋巴结疾病范围与HPV cfDNA水平相关。HPV cfDNA水平在放疗第1周达到峰值，并在治疗过程中下降。与接受标准治疗的患者相比，接受PDS0101疫苗的患者检测不到HPV 16型cfDNA的比例更高。HPV cfDNA清除与更好的2年RFS相关（92.9%对30%，对数秩检验；P = 0.0067）。RFS的最强预测因素是随访时HPV cfDNA清除，一致性指数评分为0.83，与MRI反应联合时有所改善（一致性指数，0.88）。
HPV cfDNA水平在chemoRT期间动态变化。随访时的HPV cfDNA水平可预测RFS，治疗性HPV疫苗与chemoRT联合使用与HPV cfDNA快速下降有关。在chemoRT期间和之后监测HPV cfDNA可能有助于指导个性化治疗的调整。
