Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer
Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer
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DOI：
10.1200/jco.19.02444
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发表时间：
2020-04-01
影响因子：
45.3
通讯作者：
Gupta, Gaorav P.
中科院分区：
文献类型：
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作者：
Chera, Bhishamjit S.;Kumar, Sunil;Gupta, Gaorav P.
血浆循环肿瘤人乳头瘤病毒DNA（ctHPVDNA）是人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）的敏感、特异的生物标志物。我们调查是否在治疗后监测ctHPVDNA纵向监测可以准确地检测临床疾病recursion.METHODS和absorpALSA前瞻性生物标志物的临床试验中进行非转移性HPV相关（p16阳性）OPSCC患者。所有患者均接受治疗性放化疗（CRT）。患者接受CRT后3个月的正电子发射断层扫描/计算机断层扫描，此后每2-4个月（1-2年）进行一次临床评价，然后每6个月（3-5年）进行一次临床评价。每6个月进行一次胸部影像学检查。每6-9个月采集一次血液标本，采用多分析物数字聚合酶链反应测定法分析血浆ctHPVDNA。主要终点是评估ctHPVDNA监测的阴性预测值（NPV）和阳性预测值（PPV）。中位随访时间为23个月（范围：6.1-54.7个月）后，15例患者（13%）出现疾病复发。87例患者在所有治疗后时间点均检测不到ctHPVDNA，无复发（NPV，100%; 95%CI，96%至100%）。28例患者在治疗后监测期间出现ctHPVDNA阳性，其中15例被诊断为活检证实复发。16例患者连续2次ctHPVDNA检测阳性，其中15例经活检证实复发。两次连续阳性ctHPVDNA血液检测的PPV为94%（95% CI，70%至99%）。ctHPVDNA阳性和活检证实的复发之间的中位提前时间为3.9个月（范围，0.37-12.9个月）。CONCLUSION治疗后监测期间连续两个血浆样本中ctHPVDNA的检测具有较高的PPV和NPV，用于识别HPV相关口咽癌患者的疾病复发，并可能有助于早期启动挽救治疗。(c)2020年美国临床肿瘤学会
PURPOSEPlasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.METHODS AND MATERIALSA prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.RESULTSOne hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months).CONCLUSIONDetection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy. (c) 2020 by American Society of Clinical Oncology