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; five 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.


Funding Opportunity Announcement for Clinical Sites to join the ‘CASCADE’ Network

Through the Funding Opportunity Announcement (FOA) RFA-CA-22-051, NCI will be soliciting applications from institutions/organizations to participate as international and domestic Clinical Sites for the HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network. The ‘CASCADE’ Network was launched in Fiscal Year 2022 with three organizational components through individual FOAs: the Network Coordinating Center (funded through RFA-CA-21-045), Research Bases (three organizations funded through RFA-CA-21-046), and Clinical Sites (three organizations funded through RFA-CA-21-047).

The FOA RFA-CA-22-051 (re-issue of RFA-CA-21-047) will support five additional UG1-Cooperative Agreement-funded Clinical Sites (anticipated to be two domestic and three international sites) to join the ‘CASCADE’ Network.

Applicants for UG1 Clinical Sites in RFA-CA-22-051 are expected to provide a pluripotent infrastructure for accruing participants to ‘CASCADE’ network clinical trials, interface with the Research Bases during concept and protocol development to provide insights and input on clinical significance and study feasibility, and provide on-site operational leadership for the successful conduct of the network clinical trials.

UG1 Clinical Sites applicant institutions may be located in low- and middle-income countries (LMICs)—to be led either by LMIC PI(s) or co-led by LMIC and US-based PI(s)—or can be located in regions of healthcare disparities in the US—to be led by US PI(s).

The UG1 Clinical Sites are expected to have supportive infrastructure and experience in at least three of the four scientific focus areas of the ‘CASCADE’ Network, as well as experience in providing clinical care and cancer prevention services to patients and/or communities in underserved regions and in less organized or fragmented health care systems.

Key Dates

  • Pre-application Webinar 
    November 2, 2022
  • (Optional) Letter of Intent Due Date: November 28, 2022
  • Application Due Date: December 28, 2022
  • Scientific Merit Review: March 2023
  • Advisory Council Review: May 2023
  • Earliest Start Date: July 2023

For more information, please contact

‘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

*Note: Applications for five additional Clinical Sites—both from LMICs as well as from the US—are being invited via RFA-CA-22-051 (application deadline: December 28, 2022).

More about the CASCADE Organizational Units

Frequently Asked Questions (FAQs)

Answers about:

  • Eligibility
  • Network Activities
  • Budget

Read the FAQs


Pre-application Webinar CASCADE Clinical Sites (RFA-CA-22-051)

View the recording Download slides (PDF, 1.23 MB)