HIV/Cervical Cancer Prevention ‘CASCADE’ Clinical Trials Network


NCI’s HIV/Cervical Cancer Prevention ‘CASCADE’ Clinical Trials Network (‘CASCADE’) is a cooperative agreement-funded program focused on pragmatic clinical trials to optimize the cervical cancer screening, management, and precancer treatment cascade for women living with HIV.

‘CASCADE’ network clinical trials focus on evaluating the clinical effectiveness of prevention interventions in intended-use environments while gathering crucial information to inform implementation and scale-up.

The ‘CASCADE’ network is composed of three types of organizational units working collaboratively and in partnership with the NCI to design and conduct pragmatic clinical trials with hybrid effectiveness-implementation designs, both in resource-constrained settings in low- and middle-income countries (LMICs) as well as in areas of healthcare disparities within the United States.

  • One U24 CASCADE Network Coordinating Center (CNCC) (funded via RFA-CA-21-045 in 2022)
  • Three UG1 Research Bases (RB) (funded via RFA-CA-21-046 in 2022)
  • Eight UG1 Clinical Sites (CS) (three sites funded via RFA-CA-21-047 in 2022; six additional sites to be funded via RFA-CA-22-051 in 2023)

‘CASCADE’ network clinical trials emphasize the following four scientific areas of focus for cervical cancer prevention in women living with HIV:

  • Increasing screening uptake
  • Improving management of screen positives
  • Facilitating precancer treatment access
  • Optimizing precancer treatment access

The ‘CASCADE’ Network involves collaborative development and implementation of clinical trial protocols, with shared decision making through the Network Steering Committee and complementary responsibilities in all steps from trial conceptualization to conduct.

  • Research Base investigators propose concepts that are reviewed by the ‘CASCADE’ Network Steering Committee for feasibility and recommendations for participation by individual Clinical Sites.
  • Protocol Teams composed of Research Base and Clinical Site investigators then collaboratively design the clinical trial protocols that require approval by the Network Steering Committee and an NCI Oversight Committee.
  • Protocols are activated and implemented in participating Clinical Sites after securing setting-specific ethics and regulatory approvals.
  • The Network Coordinating Center facilitates coordination, scientific review, data management, and independent risk-appropriate auditing of network clinical trials.

The ‘CASCADE’ Network Steering Committee includes representation from each of the network organizational units and the NCI.

Prioritization of clinical trial concepts and matching of Research Bases with Clinical Sites for specific protocols involves balancing competing considerations around scientific focus, availability of infrastructure, access to appropriate study populations, geographic distribution of studies across the network, trial accrual targets, protocol implementation complexity, and strategic partnership opportunities.

The ‘CASCADE’ network is expected to contribute evidence to inform clinical practice guidelines and improve implementation of cervical cancer prevention and control programs globally for women living with HIV.

‘CASCADE’ Network Organizational Units

CASCADE Network Coordinating Center (CNCC)

  • Frontier Science, with University of Wisconsin and University of California, Los Angeles

Research Bases (RB)

  • RB1: University of Washington, with Fred Hutchinson Cancer Research Center
  • RB2: Weill Medical College of Cornell University, with Moffitt Cancer Center and University of North Carolina at Chapel Hill
  • RB3: University of North Carolina at Chapel Hill

Clinical Sites (CS)

  • CS1: Uganda: Makerere University Walter Reed Project, with US Military HIV Research Program and Uganda Cancer Institute
  • CS2: Kenya: Emory University, with Coptic Hope Center for Infectious Diseases and Kenyatta National Hospital
  • CS3: Botswana: Brigham and Women's Hospital, with Botswana Harvard AIDS Institute Partnership

More about the CASCADE Organizational Units

'CASCADE' Program Guidelines

Download the 'CASCADE' Program Guidelines (PDF, 1.06 MB)

Cover page of the 'CASCADE' Program Guidelines