Prognostic value of quantitative HPV viral load in determining cervical cancer treatment response and recurrence

定量 HPV 病毒载量在确定宫颈癌治疗反应和复发方面的预后价值

• 批准号: 10399421
• 负责人: Surbhi Grover
• 金额: $ 25.04万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399421
• 关键词: Acquired Immunodeficiency Syndrome; Aftercare; Biometry; Biopsy; Botswana; Cancer Patient; Cervical; Cessation of life; Chemotherapy and/or radiation; Clinical; Clinical Trials; Clinical assessments; Cohort Studies; Combination Drug Therapy; Detection; Development; Diagnosis; Early identification; Early treatment; Enrollment; Ensure; Evaluation; Foundations; Future; Goals; Grant; HIV; HIV Infections; High Prevalence; Human; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Image; Immunologic Deficiency Syndromes; In complete remission; Intervention; Intervention Studies; Investigation; Lesion; Malaria; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Mentors; Methodology; Methods; Modeling; Molecular; Monitor; Natural History; Outcome; Parents; Patient-Focused Outcomes; Patients; Pennsylvania; Performance; Persons; Play; Polymerase Chain Reaction; Prediction of Response to Therapy; Prognostic Factor; Public Health; Radiation; Radiation Oncologist; Radiation Oncology; Recurrence; Recurrent disease; Regimen; Relapse; Research; Research Personnel; Research Project Grants; Resource-limited setting; Role; Salvage Therapy; Swab; Testing; Time; Tissues; Training; Training and Infrastructure; Treatment Failure; Tuberculosis; Tumor Burden; Universities; Videoconferencing; Viral Load result; Visit; Woman; Work; base; cancer therapy; career; chemotherapy; clinical care; co-infection; cohort; cost; cost effective; experience; follow-up; global health; high risk; improved; improved outcome; individualized medicine; innovation; low and middle-income countries; meetings; mortality; multidisciplinary; parent grant; personalized approach; personalized intervention; personalized management; personalized medicine; prognostic tool; prognostic value; programs; risk stratification; screening; skills; therapeutic vaccine; tool; translational cancer research; translational scientist; treatment response; tumor

ABSTRACT Cervical cancer is the most common cancer in women worldwide, with the highest burden in low- and middle- income countries (LMICs). Treatment of locally advanced cervical cancer includes radiation and concurrent chemotherapy (CRT). However, high rates of relapse and recurrence remain a significant problem, despite recommended treatment, particularly in LMICs. Therefore, identifying patients at high risk for treatment failure and recurrence is a critical initial step in the development of individualized management and follow-up of those patients. The overarching goal of the line of investigation proposed in this application is to allow for individualized treatment of cervical cancer patients in resource-limited settings using risk stratification models. We believe that quantification of the burden of human papillomavirus (HPV) infection will be a valuable prognostic tool for the individualized management of cervical cancer patients. More precisely, we hypothesize that quantification of the total and subtype-specific burden of HPV will predict treatment response and recurrence of cervical cancer, allowing clinicians to stratify high-risk patients at initial diagnosis and early stages of treatment. Further, quantitative HPV viral load is more accessible and cost-effective than currently recommended approaches for individualized cancer treatment, making it ideal for use in resource-limited settings. In this K08 proposal, Dr. Surbhi Grover, a trained radiation oncologist experienced in studying cervical cancer cohorts in LMICs, will determine the performance of total and subtype-specific HPV viral load as a predictor of treatment response and recurrence in cervical cancer patients treated with CRT in Botswana. Dr. Grover's overall career goal is to became an independent investigator in cervical cancer translational research and clinical trials, and to identify prognostic factors that will guide personalized interventions studied in future clinical trials to improve outcomes of cervical cancer patients in LMICs. With support from the Department of Radiation Oncology at the University of Pennsylvania (UPenn), she has been based in Botswana for the past three years working with cervical cancer patients. Dr. Grover and her multi-disciplinary team of mentors have developed a training plan that will leverage our ongoing studies in Botswana and enable her to acquire the skills needed to become a leading cervical cancer translational researcher focusing on clinical trials in LMICs. Training in clinical trials in LMICs, advanced biostatistics, and molecular methods of HPV detection and quantification will augment her training in radiation oncology and public health. The proposed study for the K08 grant will be nested in an ongoing University of Botswana and UPenn U54 consortia grant on which Dr. Grover currently plays a major role. During the course of the K08, she will continue to be based in Botswana to implement this study. She will continue to have regular video- conferencing calls and face-to-face meetings with her mentors, who will ensure that she is successful in carrying out this K08 project, in achieving her training goals, and in advancing her overall career goals.

摘要 宫颈癌是世界范围内女性最常见的癌症，中低收入人群的负担最高， 低收入国家（LMIC）。局部晚期子宫颈癌的治疗包括放射治疗和同时 化疗（CRT）。然而，高复发率和复发率仍然是一个重大问题，尽管 推荐治疗，特别是在中低收入国家。因此，识别治疗失败的高风险患者 复发是发展个体化管理和随访的关键初始步骤， 患者本申请中提出的调查路线的首要目标是允许 在资源有限的情况下，使用风险分层模型对宫颈癌患者进行个性化治疗。 我们认为，量化人乳头瘤病毒（HPV）感染的负担将是一个有价值的， 子宫颈癌患者的个体化管理的预后工具。更准确地说，我们假设 HPV的总负荷和亚型特异性负荷的定量将预测治疗反应， 宫颈癌复发，使临床医生能够在初步诊断和早期诊断时对高风险患者进行分层 治疗阶段。此外，定量HPV病毒载量比目前更容易获得且更具成本效益 推荐的个性化癌症治疗方法，使其成为资源有限的 设置.在这个K 08提案中，Surbhi Grover博士，一位在研究宫颈癌方面经验丰富的训练有素的放射肿瘤学家， 癌症队列中的LMIC，将确定总的和亚型特异性HPV病毒载量的性能， 博茨瓦纳接受CRT治疗的宫颈癌患者治疗反应和复发的预测因子。 博士格罗弗的总体职业目标是成为宫颈癌转化的独立研究者。 研究和临床试验，并确定预后因素，将指导个性化的干预研究 在未来的临床试验，以改善宫颈癌患者在LMIC的结果。的支持下 宾夕法尼亚大学（UPenn）放射肿瘤学系，她一直在 博茨瓦纳在过去三年中与宫颈癌患者一起工作。格罗弗医生和她的多学科 一组导师制定了一项培训计划，将利用我们在博茨瓦纳正在进行的研究， 她获得成为领先的宫颈癌转化研究人员所需的技能，专注于 LMICs的临床试验。LMIC临床试验培训，先进的生物统计学和分子方法 HPV检测和定量将加强她在放射肿瘤学和公共卫生方面的培训。的 K 08赠款的拟议研究将嵌套在博茨瓦纳大学和宾夕法尼亚大学U 54正在进行的研究中 格罗弗博士目前在财团赠款中发挥着重要作用。在K 08的过程中，她将 继续在博茨瓦纳开展这项研究。她将继续定期视频- 会议电话和面对面的会议与她的导师，谁将确保她是成功的， 她在执行这个K 08项目，实现她的培训目标，并在推进她的整体职业目标。