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.
Cervical cancer is a leading cause of mortality for women in low- and middle-income countries, despite receiving appropriate treatment. Our study will help develop a low-cost quantitative method based on total and subtype-specific HPV viral load to stratify women who are at a high risk of treatment failure and to guide personalized management for such patients to improve their outcomes. Findings from this study will establish a strong foundation for future studies focused on validating the clinical utility of this risk stratification model on clinical outcomes and on studying other interventions to improve outcomes of patients with cervical cancer through clinical trials.