Salivary HPV DNA informs locoregional disease status in advanced HPV-associated oropharyngeal cancer
Salivary HPV DNA informs locoregional disease status in advanced HPV-associated oropharyngeal cancer
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DOI：
10.1016/j.oraloncology.2019.06.019
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发表时间：
2019-08-01
期刊：
影响因子：
4.8
通讯作者：
Paweletz, Cloud P.
中科院分区：
文献类型：
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作者：
Hanna, Glenn J.;Lau, Christie J.;Paweletz, Cloud P.
目的：定量组织和血液循环中的肿瘤DNA可以实现高质量的分子监测，以检测和跟踪癌症的进展。评估人乳头瘤病毒（HPV）相关口咽癌（OPC）患者血液和唾液中的肿瘤DNA可为实时疾病检测提供一种无创且临床可行的方法。方法：我们之前验证了一种针对与OPC有因果关系的主要高危HPV亚型的超灵敏滴数（dd） PCR检测。在这里，我们招募了一个观察性队列来评估21例晚期HPV+OPC患者配对血浆-唾液肿瘤DNA的预测和预后潜力。结果：在复发、持续性局部区域（LR）疾病的患者中，标准化唾液HPV DNA的中位基线为10.9拷贝/ng总DNA，比仅远处疾病的患者高出近20倍（p=0.01）。5拷贝/ng的临界值准确预测LR疾病的敏感性为87%，特异性为67%。LR疾病患者的总肿瘤负荷与唾液HPV DNA水平密切相关（R=0.83, p=0.02）。唾液HPV DNA的上升和下降分别预测了所有LR疾病患者的治疗失败和反应，以及之前的影像学发现。在配对的唾液-血浆（无细胞）cfDNA样本中，只有较高的血浆HPV cfDNA水平与不良结果相关(p
Objectives: Quantifying tumor DNA in tissue and circulating in blood permits high-quality molecular monitoring to detect and track cancer progression. Evaluating tumor DNA in both blood and saliva in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) could provide a non-invasive and clinically actionable method for real-time disease detection.Methods: We previously validated an ultrasensitive droplet-digital (dd) PCR assay targeting the dominant high-risk HPV subtypes causally linked to OPC. Here we enrolled an observational cohort to evaluate the predictive and prognostic potential of paired plasma-salivary tumor DNA among 21 patients with advanced HPV+OPC.Results: In patients with recurrent, persistent locoregional (LR) disease, median baseline normalized salivary HPV DNA was 10.9 copies/ng total DNA, nearly 20x higher compared with those with distant disease only (p=0.01). A cutoff of 5 copies/ng yielded 87% sensitivity and 67% specificity for accurately predicting LR disease. Total tumor burden among those with LR disease strongly correlated with salivary HPV DNA levels (R=0.83, p=0.02). The rise and fall of salivary HPV DNA predicted treatment failure and response, respectively, in all patients with LR disease, and predated imaging findings. Among paired salivary-plasma (cell-free) cfDNA samples, only higher plasma HPV cfDNA levels were associated with poor outcomes (p