Circulating Human Papillomavirus DNA as a Biomarker of Response in Patients With Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation
Circulating Human Papillomavirus DNA as a Biomarker of Response in Patients With Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation
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DOI：
10.1200/po.18.00152
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发表时间：
2018-09-13
影响因子：
4.6
通讯作者：
Bratman, Scott, V
中科院分区：
文献类型：
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作者：
Han, Kathy;Leung, Eric;Bratman, Scott, V
目的探讨血浆人乳头瘤病毒(HPV)DNA在局部晚期宫颈癌复发前的诊断价值，并与3个月期的氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)进行比较。结果19例HPV阳性宫颈癌患者中，IB期占32%，IIB期占58%，IIIB/IVA期占10%。中位随访期为24个月(18~30个月)。所有患者治疗前均可检测到血浆HPVDNA。6名患者在CRT结束时可检测到血浆HPVDNA，其中3名患者在3个月时出现转移。到目前为止，在13名CRT结束时无法检测到血浆HPVDNA的患者中，只有一人复发。到目前为止，这13名患者中有6名在3个月的FDG-PET检查中呈阳性，在随后的影像或临床检查中没有明确的残留疾病，这6名患者中有4名在3个月时检测不到血浆HPVDNA。CRT结束时未检测到血浆HPV DNA的患者的18个月无进展生存率显著高于可检测到血浆HPV DNA的患者(92%vs50%；P=0.02)。3个月血浆HPV DNA和3个月FDG-PET显像预测18个月复发的受试者工作特征曲线下面积分别为77%和60%(P=0.008)。结论CRT结束时可检测到的血浆HPV DNA早于临床诊断转移，并与较差的无进展生存率相关。此外，3个月血浆HPVDNA水平比3个月FDG-PET显像在检测残留病方面更准确。血浆HPVDNA检测对指导辅助/挽救治疗的临床价值有待于进一步研究。(C)2018年美国临床肿瘤学会
Purpose To determine whether plasma human papillomavirus (HPV) DNA predates clinical recurrence and compare its accuracy with 3-month fluorodeoxyglucose positron emission tomography (FDG-PET) in locally advanced cervical cancer.Methods This prospective multicenter study accrued 23 women with stage IB to IVA cervical cancer planned for definitive chemoradiation therapy (CRT). Plasma HPV DNA was measured serially by digital polymerase chain reaction, and FDG-PET was performed at 3 months post-CRT.Results Of the 19 women with HPV+ cervical cancer included in this analysis, 32% were stage IB, 58% IIB, and 10% IIIB/IVA. Median follow-up was 24 months (range, 18 to 30 months). All patients had detectable plasma HPV DNA before treatment. Six patients had detectable plasma HPV DNA at the end of CRT, and three of them developed metastases at 3 months. Of the 13 patients with undetectable plasma HPV DNA at end of CRT, to date, only one has developed recurrence. Six of those 13 patients had a positive 3-month FDG-PET with no definite residual disease on subsequent imaging or clinical examination to date, and four of these six had undetectable plasma HPV DNA at 3 months. Patients with undetectable plasma HPV DNA at end of CRT had significantly higher 18-month progression-free survival than those with detectable plasma HPV DNA (92% v 50%; P = .02). The area under the receiver operating characteristic curve (accuracy) of 3-month plasma HPV DNA and 3-month FDG-PET imaging for predicting recurrence at 18 months were 77% and 60%, respectively (P = .008).Conclusion Detectable plasma HPV DNA at end of CRT predates the clinical diagnosis of metastases and is associated with inferior progression-free survival. Moreover, 3-month plasma HPV DNA level is more accurate than 3-month FDG-PET imaging in detecting residual disease. The clinical utility of plasma HPV DNA detection for guiding adjuvant/salvage therapy should be evaluated in future studies. (C) 2018 by American Society of Clinical Oncology