PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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). CONCLUSION 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.

中文翻译：

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血浆循环肿瘤 HPV DNA 用于监测 HPV 相关口咽癌的癌症复发

目的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) 的敏感且特异的生物标志物。我们研究了治疗后监测期间 ctHPVDNA 的纵向监测是否能够准确检测临床疾病复发。方法和材料 在非转移性 HPV 相关（p16 阳性）OPSCC 患者中进行了一项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）治疗。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（第 1-2 年）、然后每 6 个月（第 3-5 年）进行一次临床评估。每 6 个月进行一次胸部影像学检查。每 6-9 个月收集一次血液样本，使用多分析物数字聚合酶链反应测定法对血浆 ctHPVDNA 进行分析。主要终点是估计 ctHPVDNA 监测的阴性预测值 (NPV) 和阳性预测值 (PPV)。结果 纳入了 115 名患者，分析了 1,006 份血液样本。中位随访时间为 23 个月（范围为 6.1-54.7 个月）后，15 名患者（13%）出现疾病复发。87 名患者在治疗后的所有时间点都检测不到 ctHPVDNA，并且没有人出现复发（NPV，100%；95% CI，96% 至 100%）。28 名患者在治疗后监测中 ctHPVDNA 呈阳性，其中 15 名患者经活检证实复发。16 名患者连续 2 次 ctHPVDNA 血液检测呈阳性，其中 15 名患者出现活检证实复发。连续两次 ctHPVDNA 血液检测呈阳性，PPV 为 94%（95% CI，70% 至 99%）。ctHPVDNA 阳性与活检证实复发之间的中位时间为 3.9 个月（范围为 0.37-12.9 个月）。结论 在治疗后监测期间检测两个连续血浆样本中的 ctHPVDNA 具有较高的 PPV 和 NPV，可用于识别 HPV 相关口咽癌患者的疾病复发，并可能有助于更早开始挽救治疗。