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

摘要 宫颈癌是全球女性最常见的癌症，中低位患者负担最高。 收入国家(LMIC)。局部晚期宫颈癌的治疗包括放疗和同期 化疗(CRT)。然而，高复发率和复发率仍然是一个重大问题，尽管 推荐的治疗方法，特别是在LMICs中。因此，确定治疗失败的高危患者 复发是发展个性化管理和对这些患者进行跟踪的关键的第一步 病人。本申请中提出的调查路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下对宫颈癌患者进行个体化治疗。 我们相信，量化人类乳头瘤病毒(HPV)感染的负担将是有价值的 宫颈癌患者个体化管理的预后工具。更准确地说，我们假设 对HPV总负担和亚型特定负担的量化将预测治疗反应和 宫颈癌复发，使临床医生能够在最初诊断和早期对高危患者进行分层 治疗阶段。此外，定量HPV病毒载量比目前更容易获得，也更具成本效益 推荐的个性化癌症治疗方法，使其非常适合在资源有限的情况下使用 设置。在这份K08提案中，Surbhi Grover博士是一位训练有素的放射肿瘤学家，在研究宫颈方面经验丰富 LMICs中的癌症队列，将决定总HPV病毒载量和亚型特异性HPV病毒载量作为 博茨瓦纳接受CRT治疗的宫颈癌患者的治疗反应和复发的预测因子。 格罗弗博士的整个职业目标是成为一名宫颈癌翻译的独立调查员 研究和临床试验，并确定将指导所研究的个性化干预的预后因素 在未来的临床试验中，以改善LMICs中宫颈癌患者的预后。得到了来自 宾夕法尼亚大学(UPenn)放射肿瘤学系 博茨瓦纳在过去的三年里一直致力于治疗宫颈癌患者。格罗弗博士和她的多学科 导师团队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，并使 她需要获得成为一名领先的宫颈癌翻译研究人员所需的技能，专注于 LMIC的临床试验。LMICs临床试验、高级生物统计学和分子方法方面的培训 HPV检测和量化将加强她在放射肿瘤学和公共卫生方面的培训。这个 K08拨款的拟议研究将嵌套在正在进行的博茨瓦纳大学和宾夕法尼亚大学U54 格罗弗博士目前在财团拨款方面发挥了重要作用。在K08的过程中，她将 继续以博茨瓦纳为基地实施这项研究。她将继续有常规的视频- 与她的导师举行电话会议和面对面的会议，他们将确保她在 执行这个K08项目，实现她的培训目标，推进她的整体职业目标。

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.