Plasma HPV cell-free DNA monitoring in advances HPV-associates oropharyngeal cancer
Plasma HPV cell-free DNA monitoring in advances HPV-associates oropharyngeal cancer
复制标题
DOI：
10.1093/annonc/mdy251
复制
发表时间：
2018-09-01
影响因子：
50.5
通讯作者：
Paweletz, C. P.
中科院分区：
文献类型：
--
作者：
Hanna, G. J.;Supplee, J. G.;Paweletz, C. P.
背景：测量血液和组织中的游离 (cf)DNA 作为癌症疾病监测的微创方法具有巨大潜力。发生于口咽部并与人乳头瘤病毒 (HPV) 存在因果关系的癌症代表了检验这些方法的理想模型。患者和方法：我们设计了一种超灵敏定量液滴数字 (dd)PCR 检测方法来检测与口咽癌 (OPC) 相关的五种主要高危 HPV 亚型。我们招募了由 22 名晚期 HPV+ OPC 患者组成的试点观察队列，以评估我们检测的临床实用性，并探索其预测和预后潜力。结果：在该队列规模下，总肿瘤负荷 (TTB) 与 HPV cfDNA 水平密切相关（R = 0.91，P = 23 x10(-6)），并且在大多数情况下，更远的解剖疾病位置预测 HPV cfDNA 水平会增加。在重新分期扫描确认治疗反应或进展之前，所有参与者的 HPV cfONA 水平在平均 16 天（范围 12-38）内均出现相应变化。头颈部局部疾病或仅肺部转移的患者预后较差（P = 0.01）。 TTB 和中位血浆 HPV cfDNA 水平与生存率呈负相关（分别为 R= -0.65，P = 0.01；R=-0.48，P = 0.05）。结论：血浆 HPV cfDNA 监测概括了疾病状态的波动。虽然基于血液的 HPV DNA 监测目前在管理 HPV OPC 方面尚无作用，但这些数据说明了其在精准医疗时代的广泛临床潜力。
Background: Measuring cell-free (cf)DNA in blood and tissues holds significant potential as a minimally invasive method for disease monitoring in cancer. Cancers arising in the oropharynx and causally linked to human papillomavirus (HPV) represent an ideal model in which to interrogate these methods.Patients and methods: We designed an ultrasensitive and quantitative droplet digital (dd)PCR assay to detect the five dominant high-risk HPV subtypes linked to oropharyngeal cancer (OPC). We enrolled a pilot observational cohort of 22 patients with advanced HPV+ OPC to evaluate the clinical utility of our assay and explore its predictive and prognostic potential.Results: Total tumor burden (TTB) strongly correlated with HPV cfDNA levels (R = 0.91, P = 23 x10(-6)) at this cohort size, and in most cases more distant anatomic disease locations predicted increasing HPV cfDNA levels. All participants demonstrated a corresponding change in their HPV cfONA levels at a median of 16 days (range 12-38) before restaging scans confirming treatment response or progression. Patients with locoregional disease in the head and neck or pulmonary-only metastases had worse outcomes (P = 0.01). Both TTB and median plasma HPV cfDNA levels negatively correlated with survival (R= -0.65, P = 0.01; R=-0.48, P = 0.05, respectively).Conclusion(s): Plasma HPV cfDNA monitoring recapitulates fluctuations in disease status. While blood-based HPV DNA monitoring does not currently have a role in managing HPV OPC, these data speak to their broad clinical potential in an era of precision medicine.