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

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PROJECT SUMMARY This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 21-033. The COVID-19 pandemic dramatically and rapidly altered the delivery of cancer care globally, providing a compelling opportunity to empirically study how the pandemic and subsequent practice changes impacted patients and treatment pathways. Cervical cancer is one of the most common female cancers worldwide with over 600,000 new cases and 340,000 deaths estimated in 2020. The vast majority of incident cases and deaths occur in low- and middle-income countries (LMICs), particularly those with high rates of human immunodeficiency virus (HIV) as cervical cancer is an HIV-associated and acquired immunodeficiency syndrome (AIDS)-defining malignancy. In Botswana, a Sub-Saharan African country that is burdened with high rates of cervical cancer (incidence rate of 34.4 per 100,000) and HIV (18.5% prevalence), advanced stage at diagnosis and poor treatment completion contribute to high rates of mortality (20.1 per 100,000) in both HIV-positive and HIV-negative women. Despite this substantial burden, very few studies have focused on understanding modifiable drivers of treatment delays in Botswana. Furthermore, little is known regarding which interventions may be most impactful and sustainable to improve timeliness of care in LMICs before, during, or after the pandemic. As such, there is a critical need to identify effective strategies to ensure timely initiation and completion of treatment, and to understand contextual factors that may shape response to interventions. Prior to the COVID- 19 pandemic, our quantitative and qualitative data from an existing cohort of over 1,000 women receiving treatment for advanced cervical cancer in Botswana documented substantial delays in diagnostic testing and treatment initiation, driven by myriad challenges including patient knowledge and awareness, geographic and structural barriers, and limited healthcare resources. Expanding upon this prior work, the objective of this project is to: 1) quantitatively evaluate patterns of treatment initiation and completion for cervical cancer during the COVID-19 pandemic using an existing cohort of patients receiving care for advanced cervical cancer at Princess Marina Hospital in Gaborone, Botswana; and 2) qualitatively assess contextual determinants (e.g., patient fear, social distancing policies, shifts to telemedicine) contributing to experiences and timeliness of care and identify intervention strategies to target contextual determinants using the Expert Recommendations for Implementing Change (ERIC) framework. The results of this project will provide empirical data on how the COVID-19 pandemic impacted cervical cancer care and provide scientific knowledge on how different delivery approaches may have shaped outcomes for patients in Botswana. This project will also identify contextually-aligned interventions to be tested in a future implementation trial and generate fundamental evidence needed to mitigate impact of future pandemics on cancer control. The long-term goal of this project is to decrease cervical cancer mortality in LMICs by developing effective interventions that can be feasibly implemented and sustained in low-resource settings.