Kaposi's sarcoma in Malawi

Kaposi's sarcoma is the leading cancer in much of sub-Saharan Africa [1]. HIV has resulted in a dramatic increase in Kaposi's sarcoma throughout the region due to high overlapping prevalence of HIV and the etiologic agent of Kaposi's sarcoma, Kaposi's sarcoma–associated herpesvirus (KSHV) [2]. Kaposi's sarcoma is divided into four major categories: classical, iatrogenic, AIDS-related, and endemic. Endemic Kaposi's sarcoma is the only Kaposi's sarcoma subtype in which a specific immune disturbance is not readily apparent [3]. In Malawi, Kaposi's sarcoma is the leading cancer overall accounting for 34% of all malignancies recorded in the national cancer registry [4]. In a setting of high Kaposi's sarcoma burden, we sought to describe contemporary burden and characteristics of Kaposi's sarcoma in the HIV-positive and HIV-negative populations at a national teaching hospital in the capital, Lilongwe. We analyzed Kaposi's sarcoma cases from May 2014 until May 2016 in the Kamuzu Central Hospital Cancer Registry, which involves active registration of cancer cases across all hospital departments using standardized data collection forms. We identified 237 overall Kaposi's sarcoma cases, of which 153 were confirmed HIV-positive and 21 confirmed HIV-negative. Kaposi's sarcoma diagnoses were histologically confirmed in 39% (92/237) of cases overall, including 33% (50/153) of confirmed HIV-positive and 71% (15/21) of confirmed HIV-negative cases. We abstracted tumor location and subtype from all confirmed histology reports. As expected, Kaposi's sarcoma patients were more commonly men regardless of HIV status (Table 1). Age distribution was significantly different based on HIV status [P = 0.012, Fisher's exact test, Figure, Supplemental Digital Content 1, https://links.lww.com/QAD/B18; graph of Kaposi's sarcoma age distribution within HIV+ and HIV− by decade]. HIV-positive cases primarily presented during young-to-mid-adulthood with 68% of cases occurring between 20 and 49 years of age. By contrast, HIV-negative cases were more evenly distributed among age groups. HIV-positive Kaposi's sarcoma tended to present with disease at diverse anatomical sites, whereas HIV-negative Kaposi's sarcoma appeared to primarily present in the lower extremities (60%). Similarly, lesion descriptions in pathology reports suggested greater lesion heterogeneity among HIV-positive patients, with predominantly plaque or nodular lesions among HIV-negative patients (73%). Finally, among patients for whom the primary treatment modality was recorded, 49% of HIV-positive patients and 33% of HIV-negative patients received chemotherapy. Of note, radiotherapy is not available in Malawi.Table 1: Kaposi's sarcoma demographics at Kamuzu Central Hospital.These findings suggest that, despite a high HIV prevalence in Malawi, HIV-negative endemic Kaposi's sarcoma represents at least 9% of contemporary Kaposi's sarcoma burden at a national teaching hospital, with possible differences in presenting characteristics between HIV-positive and HIV-negative patients. Despite major investments and research programs in the region focused on AIDS-related Kaposi's sarcoma, endemic Kaposi's sarcoma has received relatively little attention. At our center, endemic Kaposi's sarcoma appeared to occur at both younger and older ages compared with HIV-positive Kaposi's sarcoma. Lifelong KSHV infection in sub-Saharan Africa is often acquired in childhood through salivary and breast milk transmission, although KSHV may also be acquired in adulthood. Subsequent infection with HIV during adulthood abruptly alters host immune function allowing Kaposi's sarcoma development, accounting for high Kaposi's sarcoma burden in the HIV-positive population between ages 20 and 49 years. In the absence of HIV, precipitating cofactors of endemic Kaposi's sarcoma remain unclear and may be associated with volcanic soils, African natural products, and genetic predisposition [5–7]. As antiretroviral therapy (ART) scale-up continues in Malawi, which began in 2004, with ART coverage now reaching 67% of eligible HIV-positive patients [8], the incidence of AIDS-associated Kaposi's sarcoma is anticipated to decline. These trends, coupled with demographic shifts in sub-Saharan Africa with aging of populations overall, may result in higher proportions of Kaposi's sarcoma in older individuals and relatively constant burden among children, regardless of HIV status. At our center, many of these patients had severe enough disease to require treatment with chemotherapy at a tertiary referral oncology clinic. This may become increasingly important as treatment of older patients with cytotoxic therapy is challenging in resource-limited settings without appropriate supportive care infrastructure. Novel treatment paradigms, including greater application of noncytotoxic therapies and local treatments for limited-stage disease, may therefore be needed. Finally, questions remain as to how endemic Kaposi's sarcoma evolves from KSHV infection. Studies in the United States and Malawi suggest the presence of at least two subtypes of Kaposi's sarcoma on the basis of gene expression profiling [9,10]. Understanding precipitating and viral factors in HIV-negative populations may help guide therapy development and prevention efforts. In conclusion, embedded efforts to better understand endemic Kaposi's sarcoma are needed within larger regional initiatives focused on AIDS-related Kaposi's sarcoma. If successful, such efforts have the potential to guide prevention and treatment strategies, which can better address overall Kaposi's sarcoma burden in Malawi and comparable settings, as ART scale-up continues and populations continue to age. Acknowledgements K.M.H. performed primary data analysis and manuscript preparation. M.-J.H. contributed to establishing the cancer registry and data acquisition. T.v.d.G. performed all statistical analysis. A.M., S.P., and S.G. treated patients included in the study. D.P.D., B.D., and S.G. provided funds for both the cancer registry and the study performed. All authors contributed to manuscript preparation via helpful discussions and text edits. NIH grants CA019014, CA190152, CA192744, CA210285, DE018281, CA163217, U54CA190152, P30CA016086, and 5T32AI007419-23 and the MEPI grant U2GPS001965. S.G., A.M., and D.P.D. are investigators of the AIDS malignancies consortium (2UM1CA121947). B.D. is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Infectious Disease. K.M.H. also received funding from a University of North Carolina global health award. Conflicts of interest There are no conflicts of interest.