Purpose: The 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 Design: Sixty-six patients with locally advanced cervical cancer were enrolled between 2017 and 2023. 49 received standard-of-care (SOC) treatment and 17 participated in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3-4 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. 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 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). Conclusions: HPV cfDNA levels change dynamically during chemoRT. HPV cfDNA at follow-up predicts RFS. 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.

中文翻译：

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人瘤病毒循环游离 DNA 动力学在接受根治性放化疗的宫颈癌患者中的作用


目的：人瘤病毒 （HPV） 是宫颈癌的重要原因。我们假设在放化疗 （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。实验设计： 2017 年至 2023 年间纳入了 66 例局部晚期宫颈癌患者。49 例接受了标准护理 （SOC） 治疗，17 例参加了结合治疗性 HPV 疫苗的临床试验 （PDS0101;IMMUNOCERV）。在基线、化疗 1 、 3 和 第 5 周以及化疗后 3-4 个月收集血浆。使用靶向 13 种高危型 HPV E6/E7 癌基因的液滴数字 PCR 对 HPV cfDNA 进行定量。在基线和近距离放射治疗前进行 MRI 检查。结果： 中位随访时间为 23 个月，2 年无复发生存率 （RFS） 为 78.4%。基线淋巴结疾病范围与 HPV cfDNA 水平相关。HPV cfDNA 水平在放疗第 1 周达到峰值，并通过治疗降低。与 SOC 相比，接受 PDS0101 疫苗的患者检测不到 HPV 16 型 cfDNA 的比率更高。HPV cfDNA 清除率与更好的 2 年 RFS 相关 （92.9% vs. 30%，对数秩 p=0.0067）。RFS 的最强预测因子是随访中 HPV cfDNA 清除率达到一致指数 （CI） 0.83，当与 MRI 反应联合时 （CI 0.88） 有所改善。结论： HPV cfDNA 水平在化疗过程中动态变化。随访时 HPV cfDNA 可预测 RFS。使用 chemoRT 递送治疗性 HPV 疫苗与 HPV cfDNA 的快速下降有关。化疗期间和化疗后监测 HPV cfDNA 可指导个体化治疗的定制。