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: 10584473
• 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/10584473
• 关键词: Biological Assay; Blood; Body Fluids; Cancer Diagnostics; Cancer Etiology; Carcinogens; Caring; Cells; Clinical; Collaborations; Collection; DNA; Data; Decision Making; Detection; Diagnosis; Diagnostic; Disease; Drops; Environment; Evaluation; Excision; Head and Neck Cancer; Hour; Human Papillomavirus; Immunohistochemistry; Infrastructure; Institution; Kinetics; 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; Papillomavirus Transforming Protein E6; Patients; Plasma; Postoperative Period; Prevalence; Prospective cohort; Qualifying; Quality of life; Recurrence; Research; Residual Neoplasm; Retrospective cohort; Risk; Risk Factors; Saliva; Sensitivity and Specificity; Specificity; Testing; Time; United States; Viral; Virus; Work; barrier to care; biobank; cancer cell; cancer type; chemoradiation; cohort; cost; cost effective; diagnostic strategy; digital; experience; functional improvement; genome sequencing; high risk; improved; innovation; interest; liquid biopsy; oral HPV-positive head and neck cancers; personalized medicine; prognostic; prospective; standard of care; tool; treatment response; 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。 癌症是美国最常见的HPV介导的恶性肿瘤。目前的治疗方法 HPVmOPSCC导致显著的长期发病率和生活质量下降。由于HPVmOPSCC患者更多 对治疗的反应比“传统”致癌物诱导的OPSCC更快，因此在治疗后的预期寿命更长。 治愈，兴趣集中在去强化治疗，以改善功能的结果，包括使用手术作为一种治疗方法。 单一模式方法。治疗去强化的一个主要障碍是目前用于治疗的方法的不精确性。 诊断和监测疾病：1）不能纵向进行而没有明显的不便， 患者，2）依赖于用户，导致可变灵敏度和特异性，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显微镜残留疾病的存在，并且不能确定是否存在显微镜残留疾病。 术后个体化预后能力差。液体活检方法允许非侵入性， 快速、纵向监测分析物，在癌症诊断前、诊断后和诊断环境中具有巨大的潜力。 在这项提案中，我们将测试循环肿瘤HPV DNA（ctHPVDNA）可以用于准确检测 预测诊断时和术后即刻的疾病状态。为了验证这个假设，我们 已经建立了HPVmOPSCC生物储存库的多机构合作以及正在进行的前瞻性研究， 收藏.我们将：（1）确定诊断HPVmOPSCC时ctHPVDNA的临床应用， 金标准和2）确定ctHPVDNA在手术环境中的动力学，并确定 ctHPVDNA和复发的临床病理危险因素。通过这样做，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作为后续R01应用中手术后的决策工具。这样的进步将导致 HPVmOPSCC管理的范式转变，实现个性化治疗去强化， 对患有这种疾病的患者有很大的好处。

项目成果

Detection of circulating tumor human papillomavirus DNA before diagnosis of HPV-positive head and neck cancer.

在诊断 HPV 阳性头颈癌之前检测循环肿瘤人乳头瘤病毒 DNA。

• DOI: 10.1002/ijc.33996
• 发表时间: 2022
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Rettig,EleniM;Faden,DanielL;Sandhu,Shaiba;Wong,Kristine;Faquin,WilliamC;Warinner,Chloe;Stephens,Phil;Kumar,Sunil;Kuperwasser,Charlotte;Richmon,JeremyD;Uppaluri,Ravindra;Varvares,Mark;Sethi,Rosh;Hanna,GlennJ;Sroussi,Herve
• 通讯作者: Sroussi,Herve

Liquid biopsy for the diagnosis of HPV-associated head and neck cancer.

用于诊断与HPV相关的头颈癌的液体活检。

• DOI: 10.1002/cncy.22497
• 发表时间: 2022-01
• 期刊: CANCER CYTOPATHOLOGY
• 影响因子: 3.4
• 作者: Faden, Daniel L.

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

• DOI: 10.1002/cncr.34109
• 发表时间: 2022-06-01
• 期刊: Cancer
• 影响因子: 6.2