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.

项目概要 HPV 介导的口咽鳞状细胞癌 (HPVmOPSCC) 的患病率正在上升，超过了宫颈癌 癌症是美国目前最常见的 HPV 介导的恶性肿瘤。 HPVmOPSCC 导致显着的长期发病率和生活质量下降，因为 HPVmOPSCC 患者较多。 与“传统”致癌物诱发的 OPSCC 相比，对治疗的反应更灵敏，因此治疗后的预期寿命更长 治愈后，人们的兴趣集中在去强化治疗以改善功能结果，包括使用手术作为治疗方法 单一模式方法的一个主要障碍是目前治疗方法的不精确性。 诊断和监测以下疾病： 1) 不能纵向进行，否则会造成重大不便 患者，2) 取决于用户，导致敏感性和特异性不同，3) 成本高，4) 可以 此外，所有现有方法都无法确定微观残留疾病的存在，并且具有侵入性。 术后个体化预后能力较差，液体活检方法无法进行非侵入性、 对分析物进行快速、纵向监测，在癌症治疗前、治疗后和诊断中具有巨大潜力。 在本提案中，我们将测试循环肿瘤 HPV DNA (ctHPVDNA) 可用于准确检测这一假设。 预测诊断时和手术后的疾病状态为了检验这一假设。 已经建立了 HPVmOPSCC 生物样本库的多机构合作以及正在进行的前瞻性研究 我们将：(1) 确定 ctHPVDNA 在诊断 HPVmOPSCC 时的临床效用。 金标准和 2) 确定 ctHPVDNA 在手术环境中的动力学并定义之间的关系 ctHPVDNA 和复发的临床病理学危险因素在此过程中，我们将填补该领域的关键空白，建立。 必要的协作基础设施，并生成启动前瞻性评估所需的初步数据 ctHPVDNA 在随后的 R01 应用中作为手术后的决策工具。 通过实现个性化去强化治疗，HPVmOPSCC 的管理范式发生转变， 对患有这种疾病的患者有显着的益处。