Map of Malawi.
Figure 1. Map of Malawi. Lilongwe, in the central region, is the capital and largest city. Blantyre, in the more densely populated southern region, is the second largest city and historical commercial center. Both cities have estimated populations of just over 1,000,000 residents.

Malawi and HIV

Malawi is a small country in southern Africa, with 15 million people, of whom 84% live in rural areas (see figure 1). In Malawi, the life expectancy is 55 years, the gross domestic product per capita 388 USD, and the Human Development Index rank is 170 out of 187 countries. HIV prevalence is high. It has dropped from 16.4% in 1999 to 10.6% in 2010 due to national antiretroviral therapy (ART) scale-up, which started in 2004. Since then there has been a greater than 100-fold increase in the number of HIV-infected individuals accessing ART. Out of the estimated 1,100,000 HIV-positive Malawians, approximately 67% of those needing ART received it in 2014. For patients initiating ART, just 77% are still alive and on ART one year after starting.

Despite having more limited resources than many neighboring countries, Malawi has been a regional leader in scaling up ART using an inclusive public health approach. As an example, in 2011 Malawi became the first country in sub-Saharan Africa to offer universal lifelong ART to HIV-infected pregnant women (Option B+) irrespective of CD4 count. This approach has since been adopted in a number of other countries, in an effort to eliminate vertical HIV transmission and improve maternal health.

 

HIV and cancer in Malawi

HIV data is limited in the Malawi National Cancer Registry (MNCR), making definitive conclusions about HIV effects on cancer incidence difficult. However, 12,301 of 18,855 (65.2%) cancers in Malawi between 2007 and 2010 were one of the three classical AIDS-defining cancers (ADC). Kaposi sarcoma (KS) accounted for 34.1%, cervical cancer for 25.4%, and non-Hodgkin lymphoma (NHL) 5.7% of all cancer cases. HIV status for individual cases was not always known, but the effects of HIV on this distribution are clear. Even though national ART scale-up began in 2004, incidence for KS and cervical cancer were still increasing between 2007 and 2010 (Figure 2). Although this may partly reflect more frequent cancer diagnosing, these data from a national population-based cancer registry are concerning. Of note, Malawi is one of only four countries in sub-Saharan Africa in the current tenth volume of Cancer Incidence in Five Continents (CI5X), reflecting the high quality of the national cancer surveillance effort.

Trends in cancer incidence
Trends in cancer incidence in males (top) and females (bottom) in Malawi, from 1999 to 2010. Data from Msyamboza et al., BMC Res Not, 2012, 5:149.

 

Malawi cancer infrastructure

Malawi is the ideal setting to study HIV-associated cancers. Despite fewer resources than many of its neighbors, a remarkable network for cancer research exists as reflected in the diverse and accomplished partner institutions for this consortium. NCI support to UNC-MCC is anticipated to have major catalytic effects on the national agenda. It will provide opportunities for high-caliber research in this setting. Key findings may be more transferable to much of sub-Saharan Africa than from higher-income countries in the region.

Malawi is small, with high HIV prevalence, and high population density, facilitating patient enrollment and retention in clinical studies focused on HIV-associated malignancies. Cancer care is centralized in Lilongwe and Blantyre, which are geographically close, providing opportunities to implement protocols with nearly national coverage across large population referral bases.

Cancer is a high priority for the Malawi Ministry of Health (MOH). A national cancer plan incorporating WHO recommendations has been articulated. Plans have been finalized with the International Atomic Energy Agency (IAEA), to develop a Cancer Center of Excellence at Kamuzu Central Hospital (KCH) in Lilongwe, which is anticipated to have radiotherapy, a range of chemotherapy medicines, diagnostic capabilities including pathology and computed tomography (CT), and required specialists to provide multidisciplinary care. UNC Project-Malawi, Lighthouse Trust, and University of Malawi College of Medicine (COM) faculty have participated in IAEA delegation visits to assist in strategic planning at the invitation of MOH.

 

Herpesvirus-associated cancers in Malawi

Our consortium is focused on cancers caused by herpesviruses. Two of the three main ADCs are in this category. For KS, by far the most common cancer in Malawi, all cases are caused by Kaposi sarcoma-associated herpesvirus (KSHV), which was first discovered in association with the tumor in 1994. High KS burden in Malawi partly reflects overlapping high prevalence for HIV and KSHV. For lymphoma, 40-60% of HIV-associated NHL cases are caused by another herpesvirus, Epstein-Barr virus (EBV), although rates of EBV detection in tumor specimens vary significantly across histologic NHL subtypes. For Hodgkin lymphoma (HL), which is also associated with HIV and which may be proportionally increasing among lymphoma subtypes in the ART era, EBV is found in >80% of tumor specimens. However, nearly all lymphoma data is derived from resource-rich settings, and the contribution of EBV to lymphomas occurring in the Malawian HIV-infected population is still unknown, particularly given that sub-Saharan Africa is enriched overall for infectious cancers compared with other parts of the world. Moreover, KSHV can be infrequently associated with less common NHL subtypes (primary effusion lymphoma, or PEL; plasmablastic lymphoma arising from multicentric Castleman Disease, or MCD). These diseases are rarely diagnosed in sub-Saharan Africa, which most likely reflects underdiagnosis.