The global economic toll of cancer is >$1 trillion annually, greater than for any other disease. Worldwide, >70% of cancer cases occur in LMICs, where cancer causes more deaths than HIV, tuberculosis, and malaria combined. Additionally, >2 million lives could be saved each year in LMICs with appropriate investments in cancer control. However, there is no large scale international effort to address cancer in LMICs that is remotely comparable to what has been accomplished for HIV through the Global Fund, PEPFAR, or other initiatives, with respect to funding levels, prioritization, coordination, or implementation. In Malawi, basic cancer control elements remain either absent or severely limited, and the country suffers from only four pathologists, three oncologists, no radiotherapy, non existent early detection, and erratic supply of essential medicines for treatment and palliation. Moreover, given competing priorities and funding sources for various cancer types, and diverse opportunities for intervention (prevention, early detection, treatment, palliation), there is no implementation framework to guide the optimal translation of what is known, with defined deliverables and metrics for evaluation, toward an effective and comprehensive cancer control strategy that best serves the Malawian people. Our proposal will leverage the national cancer research program we have built in Malawi, to develop a parallel implementation framework, informing and catalyzing future PEPFAR like initiatives to address global cancer burden.
Annual health expenditure per capita is $29 in Malawi (versus $9,403 in the US). By adding ~$1 per capita per year ($100 million over six years and 17.5 million Malawians), we will achieve unprecedented '50 50 50 50' targets for cancer control: (1) 50% decrease in incidence for preventable cancers; (2) 50% increase in proportion of cancers diagnosed at early stages; (3) 50% increase in proportion of patients with curable cancers alive in remission at two years; (4) 50% increase in proportion of patients with incurable cancers who receive effective palliation. The '50 50 50 50' metrics will be assessed across the five commonest cancers in Malawi: Kaposi sarcoma, cervical cancer, esophageal cancer, breast cancer, and lymphoma. Relative to alternative solutions, our approach addresses the lack of coordination, inefficiencies, and skewed prioritization resulting from piecemeal cancer control efforts, driven by diverse funders, focused on various cancers, and subject to diverse political pressures. We will accomplish our solution by developing and implementing a coordinated national package of cancer control interventions, informed by scientific, technical, and programmatic assistance from within and outside Malawi, focused on achievability and translating proven strategies to a population level. Effects will be sustained for decades by creating a stable, multilateral, coordinated research translation framework for cancer with high level Malawian ownership, training and capacity building to allow eventual handover to Malawi partners, sustained benefits from focused interventions on specific cancer types, operational insights provided to other LMIC cancer control programs, and economic impact data provided to donors making commitments for cancer control in LMICs.
Evidence of Effectiveness
There has been no comparably ambitious attempt to solve cancer at a national scale in LMICs. However, each component intervention is proven. Analogously, HIV treatment was proven before LMIC implementation, but implementation in LMICs itself required evidence to dissuade skeptics. For target 1, human papillomavirus causes >90% of cervical cancer worldwide. Vaccination prevents pre cancers and cancers, and has been accepted by patients in small Malawi pilot studies. Additionally, cervical cancer screening using visual inspection and acetic acid (VIA) is effective to find and ablate pre cancers, reducing disease specific mortality. For target 2, early cancer detection in LMICs leads to tumor down staging with improved outcomes, doubling rates of early breast cancer diagnosis for example. Additionally, pathology models appropriate for LMICs, including remote virtual microscopy, are achievable and reduce waiting times to cancer diagnosis. For target 3, evidence based cancer treatment guidelines improve outcomes worldwide. Moreover, many cancers are curable even in LMICs when old generic medicines are available and administered in standardized protocols with structured supportive care to minimize toxicity. For target 4, early palliation for advanced tumors improves quality of life and survival, and effective palliation is possible even in LMICs, including support for patients within communities. Finally, for many component interventions, key evidence from LMICs has actually been generated within our group at UNC and in Malawi, including for VIA scale up, clinical breast exam screening, pathology capacity building, cancer registration, curative lymphoma treatment, and community level palliation. Thus, we have helped create setting appropriate evidence to guide our broader implementation effort.
Over more than two decades, we have generated paradigm shifting science for HIV in Malawi, including the landmark study providing definitive evidence for HIV 'treatment as prevention' now being implemented worldwide. We have also worked with MOH to provide technical assistance for expanding HIV services, by contributing to national guidelines and launching programs to halt perinatal HIV transmission. More recently, we have developed one of the world's leading LMIC cancer research programs. Our cancer portfolio spans the population, clinical, and basic sciences, and includes each of Malawi's highest burden cancers along with diagnostic pathology as a foundation. Efforts have included: (1) leading the first multinational clinical trials for Kaposi sarcoma in LMICs and providing first evidence of possible molecular subtypes; (2) supporting cervical cancer screening implementation and clinical trials to define optimal screening methods in LMICs; (3) defining genomic signatures for esophageal cancer which suggest a possible novel carcinogen, and undertaking epidemiologic studies to identify environmental exposures responsible for high disease incidence; (4) conducting Malawi's first breast cancer screening study demonstrating high feasibility, acceptability, and uptake; and (5) developing platforms to cure lymphoma patients more often through biologic insights and new 'targeted' agents previously unavailable in our setting. These efforts have led to a remarkable publication record, successful competition for every major recent funding opportunity for cancer in LMICs, and recent new funding from the National Cancer Institute to leverage our Malawi cancer program for initiating a Regional Center of Research Excellence for non communicable diseases.
The University of North Carolina (UNC) has collaborated with the Malawi Ministry of Health (MOH) in Lilongwe since the early 1990s to conduct research, provide care, and build capacity with a primary focus on HIV and other infectious diseases. More recently, the program has experienced rapid growth and diversification of its portfolio with cancer now being a key concentration area, due to its emergence as a leading cause of death and disability in Malawi. Together with MOH, the University of Malawi College of Medicine (COM), and other academic and non governmental partners, UNC initiated the Malawi Cancer Consortium in 2014, which has become one of the world's leading cancer research programs in LMICs. UNC is also leading an effort with partners to establish a Regional Center of Research Excellence for non communicable diseases in Malawi. The current proposal to develop an implementation/translation arm will complement and strengthen these core activities.
Our Malawi Cancer Consortium and Regional Center for Research Excellence for non communicable diseases are collaborations between UNC, MOH (which oversees the country's health system), and COM (the country's only medical school and academic health sciences institution). Organizational structures are formalized through memoranda of understanding and financial subcontracts with defined budgets and scopes of work, according to US government regulations, since current funding comes principally from the National Institutes of Health with annual disbursement contingent on satisfactory progress reports. The team is led by Dr. Satish Gopal, a medical oncologist and cancer researcher living in Malawi affiliated with UNC and COM. Involvement by MOH is coordinated by Dr. Jones Masiye, who heads the non communicable diseases unit, and COM participation is led by Dr. Mwapatsa Mipando, the institution's principal. Individual projects and core facilities, including a dedicated administrative unit, benefit from balanced leadership between foreign and Malawi partners, facilitated by regular email and conference calls. Regular meetings also occur, for example, an inaugural Malawi Cancer Symposium held in August 2016 to convene cancer stakeholders from across the country, disseminate scientific and program updates, and articulate shared cancer research priorities for Malawi.