Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
Robert and Renée Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, USA.
Oral Oncol. 2019 Aug;95:120-126. doi: 10.1016/j.oraloncology.2019.06.019. Epub 2019 Jun 20.
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.
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.
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 < 0.01), suggesting that each bodily fluid provides unique information about HPV disease status.
Salivary HPV DNA provides valuable information about tumor burden and predicts treatment response in advanced HPV+OPC. Paired blood-saliva samples could be used to monitor HPV DNA with broad applications to inform diagnosis, prognosis, and surveillance in HPV-associated diseases.
量化组织中的肿瘤 DNA 和血液中的循环肿瘤 DNA，可实现高质量的分子监测，以检测和跟踪癌症进展。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非侵入性的、具有临床操作性的方法。
我们之前验证了一种针对与 OPC 因果相关的优势高危 HPV 亚型的超灵敏液滴数字（dd）PCR 检测方法。在这里，我们招募了一个观察队列，以评估 21 例晚期 HPV+OPC 患者的配对血浆-唾液肿瘤 DNA 的预测和预后潜力。
在复发、持续性局部区域（LR）疾病患者中，基线时中位正常化唾液 HPV DNA 为 10.9 拷贝/ng 总 DNA，与仅有远处疾病的患者相比，几乎高 20 倍（p=0.01）。5 拷贝/ng 的截断值可准确预测 LR 疾病，灵敏度为 87%，特异性为 67%。LR 疾病患者的总肿瘤负担与唾液 HPV DNA 水平强烈相关（R=0.83，p=0.02）。所有 LR 疾病患者的唾液 HPV DNA 升高和下降分别预测了治疗失败和反应，且早于影像学发现。在配对的唾液-血浆（无细胞）cfDNA 样本中，只有较高的血浆 HPV cfDNA 水平与不良结局相关（p<0.01），表明每种体液都提供了有关 HPV 疾病状态的独特信息。
唾液 HPV DNA 可提供有关肿瘤负担的有价值信息，并可预测晚期 HPV+OPC 的治疗反应。配对的血液-唾液样本可用于监测 HPV DNA，广泛应用于 HPV 相关疾病的诊断、预后和监测。
