Sivars Lars, Jylhä Cecilia, Crona Guterstam Ylva, Zupancic Mark, Lindqvist Britta, Nordenskjöld Magnus, Tham Emma, Hellman Kristina
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Clin Cancer Res. 2024 Jul 1;30(13):2764-2771. doi: 10.1158/1078-0432.CCR-23-3941.
Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC).
A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type-specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics.
Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1-2 months after end-of-treatment), or tumor evaluation (3-4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time.
ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.
人乳头瘤病毒（HPV）是大多数宫颈癌病例的病因，并且已显示其作为游离细胞肿瘤DNA（ctHPV DNA）释放到循环系统中。在此，我们分析ctHPV DNA是否可用作预后生物标志物和/或在局部晚期宫颈癌（LACC）中比传统方法更早地检测复发。
共纳入74例LACC患者；在基于磁珠的肿瘤活检样本检测中，74例中有66例13种高危HPV类型呈阳性。开发了HPV型特异性数字液滴PCR检测方法。然后对每位患者经活检验证的HPV类型进行纵向血浆样本分析。总共分析了418份血浆样本。对患者进行了中位37个月的随访。结果与肿瘤和临床特征相关。
治疗前血浆样本中，92.4%的样本ctHPV DNA呈阳性。与未检测到ctHPV DNA相比，治疗结束时、早期随访（治疗结束后1 - 2个月）或肿瘤评估（治疗结束后3 - 4个月）血浆中持续存在的ctHPV DNA与无进展生存期较差相关（P < 0.001）。早期随访时ctHPV状态预测疾病进展的阳性预测值为87.5%，阴性预测值为89.3%。在所有经治疗获得完全临床缓解后复发的患者（n = 10）中，在通过放射学诊断复发之前，血浆中均检测到ctHPV DNA，中位提前期为315天。
随访血浆中的ctHPV DNA是LACC患者中有前景的预后生物标志物，有助于分析治疗反应和早期检测复发。
