Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.
Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.
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DOI：
10.1158/1078-0432.ccr-17-1553
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发表时间：
2017-11-15
期刊：
影响因子：
--
通讯作者：
Cao L
中科院分区：
文献类型：
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作者：
Kang Z;Stevanović S;Hinrichs CS;Cao L
循环无细胞（ccf）人乳头瘤病毒（HPV）DNA可能作为HPV相关恶性肿瘤（包括宫颈癌）的独特肿瘤标志物。我们开发了一种方法，对HPV 16或HPV 18阳性转移性宫颈癌患者的循环HPV DNA进行基因分型和定量，用于潜在疾病监测和治疗相关决策。在这项回顾性研究中，通过双重数字液滴PCR（ddPCR）测量了来自19名转移性宫颈癌患者的血清样品中的HPV ccfDNA。9例患者接受了肿瘤浸润淋巴细胞（TIL）免疫治疗。ccfDNA数据与肿瘤HPV基因型、药物治疗和临床结果一致。在盲法试验中，19例HPV阳性转移性宫颈癌患者中有19例（100%）检测到HPV ccfDNA，但45名健康献血者中没有任何一名检测到。在来自9名接受TIL免疫治疗的患者的87份连续患者血清样本中，87份（100%）正确鉴定了患者肿瘤中的HPV基因型。在TIL治疗后经历客观癌症消退的三名患者中，在TIL输注后2-3天检测到瞬时HPV ccfDNA峰。此外，仅在两名在TIL免疫治疗后经历完全应答（CR）的患者中观察到HPV ccfDNA的持续清除。HPV ccfDNA代表了一种有前途的非侵入性HPV基因分型的肿瘤标志物，可用于选择HPV类型特异性T细胞免疫治疗的患者。它也可能在检测治疗药物的抗肿瘤活性和缓解期宫颈癌患者的长期随访中具有价值。
Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making. In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet PCR (ddPCR). Nine patients had received tumor-infiltrating lymphocyte (TIL) immunotherapy. ccfDNA data were aligned with the tumor HPV genotype, drug treatment, and clinical outcome. In blinded tests, HPV ccfDNA was detected in 19 of 19 (100%) patients with HPV-positive metastatic cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients’ tumors was correctly identified in 87 of 87 (100%) sequential patient serum samples from 9 patients who received TIL immunotherapy. In three patients who experienced objective cancer regression after TIL treatment, a transient HPV ccfDNA peak was detected 2–3 days after TIL infusion. Furthermore, persistent clearance of HPV ccfDNA was only observed in two patients who experienced complete response (CR) after TIL immunotherapy. HPV ccfDNA represents a promising tumor marker for noninvasive HPV genotyping and may be used in selecting patients for HPV type–specific T-cell-based immunotherapies. It may also have value in detecting antitumor activity of therapeutic agents and in the long-term follow-up of cervical cancer patients in remission.