Summary The Center for the AIDS Program of Research in South Africa (CAPRISA) CASCADE Clinical Trials Network Clinical Research Site, aims to provide clinical trial infrastructure and operational leadership for the conduct of pragmatic clinical trials through the CASCADE Clinical Trials Network. The proposed clinical trial site is strategically located in KwaZulu-Natal (KZN) province, the epicentre of the Human Immunodeficiency Virus (HIV) epidemic in South Africa. Due to the high background HIV prevalence in this setting, KZN province remains a region with a high burden of cervical cancer disease, despite expansion and improved access to antiretroviral treatment (ART). CAPRISA has been undertaking high-impact globally relevant and locally responsive research for nearly two decades. The Ethekwini Clinical Research Site (ECRS) is one of four clinical research sites and is based in the central business district in Ethekwini. This is a well-established research site, with over 15 years’ experience conducting high-quality clinical trials. We have established research infrastructure which supports the conduct of both CAPRISA-led research as well as National Institutes of Health (NIH) network- affiliated trials, primarily recruiting young women for participation in our trials. To date, our core focus of research has been HIV prevention, although we are equally experienced in research involving HIV pathogenesis and clinical management of women living with HIV (WLHIV). Together with previous Human Papilloma Virus (HPV) epidemiological studies undertaken by our team, we have begun preliminary work in cervical cancer screening in an ongoing CAPRISA trial, where we are evaluating HPV point-of-care testing in WLHIV. Through the CASCADE network we aim to support and advance cervical cancer prevention, through participation in clinical trials. Through our relevant clinical trial experience and scientific expertise, we are able to contribute to the four scientific focus areas proposed by the network: increasing screening uptake, improving management of screen positives, facilitating precancer treatment access and optimising precancer treatment for cervical cancer prevention in WLHIV. We have assembled a strong team of investigators to support this program, including a Principal Investigator (PI) and Co-Investigators who have led multiple HIV and COVID-19 clinical trials at a site level and are leading several NIH-funded protocols as national PIs or protocol co-Chairs. The team are able to contribute to protocol development and to provide laboratory, data management and statistical support for trials undertaken through the network. Furthermore, we are able to collaborate with the respective research bases and coordinating centers proposed by the network. Considering CAPRISA’s expertise in HIV research and preliminary work undertaken in HPV epidemiology and HPV diagnostics, we are well-placed to be a strong partner in the CASCADE network.

Project Narrative In South Africa, cervical cancer prevention remains suboptimal in regions such as KwaZulu- Natal province which has a dual burden of high Human Immunodeficiency Virus (HIV) incidence and high cervical cancer incidence. Participation in clinical trials undertaken through the CASCADE Clinical Trials Network will provide an opportunity to advance and support existing cervical cancer prevention programs in this setting. Through the network, we aim to improve on cervical cancer screening strategies and to evaluate novel treatments and interventions for women with premalignant lesions of the cervix, with a view to improve clinical outcomes and to reduce the burden on the health care system.