Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC.
Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC.
J Clin Oncol. 2020 Apr 1;38(10):1050-1058. doi: 10.1200/JCO.19.02444. Epub 2020 Feb 4.
Plasma 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.
A 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.
One 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).
Detection 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.
血浆循环肿瘤人乳头瘤病毒 DNA（ctHPVDNA）是一种敏感和特异的人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）的生物标志物。我们研究了在治疗后监测期间纵向监测 ctHPVDNA 是否能准确检测临床疾病复发。
一项针对非转移性 HPV 相关（p16 阳性）OPSCC 患者的前瞻性生物标志物临床试验。所有患者均接受根治性放化疗（CRT）。患者在 CRT 后 3 个月行正电子发射断层扫描/计算机断层扫描（PET/CT）扫描，此后每 2-4 个月（第 1-2 年），然后每 6 个月（第 3-5 年）进行临床评估。每 6 个月进行胸部影像学检查。每 6-9 个月采集血液标本，采用多分析物数字聚合酶链反应（PCR）检测分析血浆 ctHPVDNA。主要终点是估计 ctHPVDNA 监测的阴性预测值（NPV）和阳性预测值（PPV）。
共纳入 115 例患者，分析了 1006 份血样。中位随访时间为 23 个月（范围为 6.1-54.7 个月），15 例（13%）患者发生疾病复发。87 例患者在所有治疗后时间点均未检测到 ctHPVDNA，且均未发生复发（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 例经活检证实复发。16 例患者连续两次 ctHPVDNA 血检阳性，其中 15 例经活检证实复发。两次连续 ctHPVDNA 血检阳性的阳性预测值（PPV）为 94%（95%CI，70%至 99%）。ctHPVDNA 阳性与活检证实复发之间的中位领先时间为 3.9 个月（范围为 0.37-12.9 个月）。
在治疗后监测期间连续两次检测血浆 ctHPVDNA 对 HPV 相关口咽癌患者疾病复发具有较高的 PPV 和 NPV，可能有助于更早开始挽救性治疗。
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