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.

抽象的 宫颈癌是全世界女性最常见的癌症 收入国家（LMIC）。局部晚期宫颈癌的治疗包括辐射和并发 化学疗法（CRT）。但是，尽管 推荐治疗，特别是在LMIC中。因此，识别患有高风险治疗失败风险的患者 复发是开发个性化管理和随访的关键第一步 患者。本申请中提出的调查线的总体目标是允许 使用风险分层模型在资源有限的环境中对宫颈癌患者的个性化治疗。 我们认为，人类乳头瘤病毒负担（HPV）感染的量化将是有价值的 用于宫颈癌患者个性化管理的预后工具。更确切地说，我们假设 量化HPV的总和亚型特异性负担将预测治疗反应和 宫颈癌的复发，使临床医生能够在初始诊断和早期对高危患者进行分层 治疗阶段。此外，定量HPV病毒负载比目前更容易获得和成本效益 推荐的个性化癌症治疗方法，非常适合用于资源限制 设置。在这个K08的提案中，训练有素的辐射肿瘤学家Surbhi Grover博士在研究宫颈 LMIC中的癌症队列将确定总和亚型特异性HPV病毒负载的性能 预测博茨瓦纳CRT治疗的宫颈癌患者的治疗反应和复发因子。 格罗弗博士的整体职业目标是成为宫颈癌翻译的独立研究者 研究和临床试验，并确定将指导所研究的个性化干预措施的预后因素 在将来的临床试验中，以改善LMIC中宫颈癌患者的预后。在 宾夕法尼亚大学（UPENN）辐射肿瘤学系，她一直在 博茨瓦纳过去三年与宫颈癌患者一起工作。格罗弗博士和她的多学科 导师团队已经制定了一项培训计划，该计划将利用我们在博茨瓦纳正在进行的研究，并启用 她要获得成为领先的宫颈癌转化研究人员所需的技能 LMIC的临床试验。在LMIC，高级生物统计学和分子方法的临床试验中培训的培训 HPV检测和量化将增加她在放射肿瘤学和公共卫生方面的培训。这 K08赠款的拟议研究将嵌套在正在进行的博茨瓦纳大学和Upenn U54 Grover博士目前扮演重要角色的财团Grant。在K08过程中，她将 继续在博茨瓦纳实施这项研究。她将继续定期视频 - 与她的导师会议和面对面的会议，他们将确保她成功 执行这个K08项目，实现她的训练目标，并促进她的整体职业目标。