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.

项目摘要 HPV介导的口咽鳞状细胞癌（HPVMOPSCC）的患病率正在增加，超过宫颈 癌症是美国最常见的HPV介导的恶性肿瘤。当前的治疗方法 HPVMOPSCC导致长期的长期发病率和改善的生活质量。随着HPVMOPSCC患​​者的更多 对治疗的反应比“传统的”致癌物诱导的OPSCC，因此经历了更长的预期寿命 治愈，兴趣的重点是去强化治疗以改善功能结果，包括将手术用作一种 单态方法。治疗去启动的主要障碍是当前方法的暗示性质 诊断和监测疾病：1）在没有明显不便的情况下纵向执行 患者2）是用户依赖的，导致敏感性和特异性，3）成本高，4）可以是 侵入性。此外，所有现有方法均无法确定微观残留疾病的存在，并具有 在术后期间，个性化的预后能力差。液体活检方法允许无创， 快速，纵向监测分析物，并在癌症前和诊断性癌症环境中具有巨大的潜力。 在此提案中，我们将检验以下假设：循环肿瘤HPV DNA（CTHPVDNA）可用于准确 在诊断时和术后直接诊断时预测疾病状况。为了检验这一假设，我们 已经建立了HPVMOPSCC生物座席的多机构合作以及正在进行的潜在 收藏。我们将：（1）确定在HPVMOPSCC诊断时CTHPVDNA的临床实用性 金标准和2）确定手术环境中cthpvdna的动力学，并定义 复发的CTHPVDNA和临床病理风险因素。这样，我们将填补现场的关键空白，构建 必要的协作基础架构，并生成必要的初步数据，以启动对 在随后的R01应用中，CTHPVDNA作为手术后的决策工具。这样的进步会导致 通过启用个性化治疗，范式转移HPVMOPSCC的管理，并通过 对患有这种疾病的患者的重大好处。