Yin Zhuomin, Feng Tao, Xu Qing, Dai Wumin, Ni Maowei, Ni Juan, Lou Hanmei
Department of Gynecologic Radiation Oncology, (Zhejiang Key Laboratory of Radiation Oncology), Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Elife. 2025 Sep 17;13:RP101887. doi: 10.7554/eLife.101887.
Monitoring circulating HPV cell-free DNA (cfDNA) offers a minimally invasive method for surveillance in HPV-associated cancers, particularly cervical cancer. However, the role of dynamic HPV cfDNA monitoring in guiding clinical treatment decisions for recurrent or metastatic cervical cancer remains underexplored.
In this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV-positive cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker.
HPV cfDNA was detected in all 28 patients. Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern observed in individual patients (p=0.019). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3-16.9 months) prior to evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (p=0.004, 95% confidence interval (CI), 0-0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (p=0.014, 95% CI, 0.022-0.621).
Our study demonstrates that HPV cfDNA is a promising tumor marker for monitoring of recurrent or metastatic HPV-positive cervical cancer.
This work was supported by the Key R&D Program of Zhejiang (2022C04001), the Zhejiang Province Medicine and Health Science and Technology Program (2020KY454), the Zhejiang Science and Technology Department Public Welfare Project (LGF22H160075).
监测循环中的人乳头瘤病毒游离DNA（cfDNA）为HPV相关癌症，尤其是宫颈癌的监测提供了一种微创方法。然而，动态HPV cfDNA监测在指导复发性或转移性宫颈癌的临床治疗决策中的作用仍未得到充分探索。
在这项前瞻性试点观察研究中，通过数字液滴聚合酶链反应测量了28例复发性或转移性HPV阳性宫颈癌患者血清样本中的HPV cfDNA水平。将HPV cfDNA水平的结果与临床结果以及鳞状细胞癌抗原（SCC-Ag）的血清水平相匹配，以评估HPV cfDNA作为肿瘤标志物的临床潜力。
在所有28例患者中均检测到HPV cfDNA。值得注意的是，根据个体患者观察到的转移模式，基线HPV cfDNA水平中位数有所不同（p=0.019）。在评估治疗反应或疾病进展之前的中位监测期2个月（范围0.3-16.9个月）内，所有参与者的HPV cfDNA水平均有变化。在最初诊断为鳞状细胞宫颈癌的26例患者中，HPV cfDNA的阳性率为100%，SCC-Ag的阳性率为69.2%（p=0.004，95%置信区间（CI），0-0.391）。在20例接受鳞状细胞宫颈癌纵向监测的患者中，HPV cfDNA与疾病状态变化的一致性为90%，SCC-Ag为50%（p=0.014，95%CI，0.022-0.621）。
我们的研究表明，HPV cfDNA是监测复发性或转移性HPV阳性宫颈癌的一种有前景的肿瘤标志物。
本研究得到浙江省重点研发计划（2022C04001）、浙江省医药卫生科技计划（2020KY454）、浙江省科技厅公益项目（LGF22H160075）的支持。
