Cell free HPV DNA detection in the diagnostic and surgical settings

诊断和手术环境中的无细胞 HPV DNA 检测

• 批准号: 10373210
• 负责人: Daniel Faden
• 金额: $ 16.8万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373210
• 关键词: Biological Assay; Blood; Body Fluids; Cancer Diagnostics; Cancer Etiology; Carcinogens; Caring; Cells; Clinical; Collaborations; Collection; Data; Decision Making; Detection; Diagnosis; Diagnostic; Disease; Drops; Environment; Evaluation; Excision; Gold; Head and Neck Cancer; Hour; Human Papillomavirus; Immunohistochemistry; Infrastructure; Kinetics; Lead; Life Expectancy; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Mediating; Messenger RNA; Methods; Microscopic; Modality; Monitor; Morbidity - disease rate; Nature; Operative Surgical Procedures; Oropharyngeal Squamous Cell Carcinoma; Patients; Plasma; Postoperative Period; Prevalence; Prospective cohort; Quality of life; Recurrence; Research; Residual Tumors; Retrospective cohort; Risk; Risk Factors; Saliva; Sensitivity and Specificity; Specificity; Testing; Time; United States; Viral; Virus; Work; barrier to care; base; biobank; cancer cell; cancer type; cohort; cost; cost effective; diagnostic strategy; digital; experience; functional outcomes; genome sequencing; high risk; improved; innovation; interest; liquid biopsy; personalized medicine; prognostic; prospective; standard of care; tool; tumor; tumor DNA; viral DNA; whole genome

PROJECT SUMMARY HPV mediated Oropharyngeal Squamous Cell Carcinoma (HPVmOPSCC) is increasing in prevalence, surpassing cervical cancer as the most common HPV mediated malignancy in the United States. Current treatment approaches for HPVmOPSCC result in significant long-term morbidity and decreased quality of life. As HPVmOPSCC patients are more responsive to treatment than “traditional” carcinogen induced OPSCC, and thus experience longer life expectancy after cure, interest is focused on de-intensifying treatment to improve functional outcomes, including the use of surgery as a single modality approach. A major barrier to treatment de-intensification is the imprecise nature of current methods for diagnosing and monitoring disease which: 1) cannot be performed longitudinally without significant inconvenience to the patient, 2) are user dependent resulting in variable sensitivity and specificity, 3) have high costs, and 4) can be invasive. Further, all existing approaches are unable to determine the presence of microscopic residual disease and have poor individualized prognostic capacity in the post-operative period. Liquid biopsy approaches allow non-invasive, rapid, longitudinal monitoring of analytes and hold enormous potential in the pre-, post- and diagnostic cancer settings. In this proposal we will test the hypothesis that circulating tumor HPV DNA (ctHPVDNA) can be used to accurately predict disease status at the time of diagnosis and in the immediate post-operative period. To test this hypothesis, we have established a multi-institutional collaboration of HPVmOPSCC biorepositories as well as ongoing prospective collection. We will: (1) determine the clinical utility of ctHPVDNA at the time of diagnosis with HPVmOPSCC compared to the gold standard and 2) determine the kinetics of ctHPVDNA in the surgical setting and define the relationship between ctHPVDNA and clinicopathologic risk factors for recurrence. In doing so, we will fill critical gaps in the field, build necessary collaborative infrastructure, and generate preliminary data needed to launch a prospective evaluation of ctHPVDNA as a decision-making tool following surgery in a subsequent R01 application. Such an advance would lead to a paradigm shift in the management of HPVmOPSCC by enabling personalized treatment de-intensification, with significant benefit to patients suffering from this disease.

项目总结 人乳头瘤病毒介导的口咽鳞状细胞癌(HPVmOPSCC)的发病率正在上升，超过宫颈 癌症是美国最常见的HPV介导的恶性肿瘤。目前的治疗方法是 HPVmOPSCC会导致显著的长期发病率和生活质量下降。随着HPVmOPSCC患者越来越多 对治疗的反应比传统的致癌物质诱发的OPSCC更好，因此经历了更长的预期寿命 治疗方面，人们的兴趣集中在去强化治疗以改善功能结果，包括使用手术作为 单通道方法。治疗去强化的一个主要障碍是当前方法的不精确性质 诊断和监测疾病：1)不能在不给以下方面带来极大不便的情况下纵向执行 患者，2)依赖于用户，导致不同敏感性和特异性，3)具有高成本，以及4)可以 侵入性的。此外，所有现有的方法都不能确定是否存在微小的残留病，并且已经 术后个体化预后能力差。液体活组织检查方法允许无创、 快速、纵向监测分析物，并在癌症前、后和诊断环境中拥有巨大的潜力。 在这项提案中，我们将检验循环中的肿瘤HPV DNA(CtHPVDNA)可以准确地用于 在诊断时和手术后立即预测疾病状态。为了检验这一假设，我们 已经建立了HPVmOPSCC生物库的多机构协作，以及正在进行的前景 收集。我们将：(1)在诊断为HPVmOPSCC时确定ctHPVDNA的临床实用性。 金标准和2)确定ctHPVDNA在手术环境中的动力学，并定义 CtHPVDNA与复发的临床病理危险因素在这样做的过程中，我们将填补该领域的关键空白，建立 必要的协作基础设施，并生成启动预期评估所需的初步数据 在随后的R01应用中，ctHPVDNA作为手术后的决策工具。这样的进步将导致 通过实现个性化治疗去强化，实现HPVmOPSCC管理的范式转变， 对患有这种疾病的患者有显著的好处。