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Objective: Cancer incidence and mortality rates in Africa are increasing, yet their geographic distribution and determinants are incompletely characterized. The present study aims to establish the spatial epidemiology of cancer burden in Africa and delineate the association between cancer burden and the country-level socioeconomic status. The study also examines the forecasts of the cancer burden for 2040 and evaluates infrastructure availability across all African countries., Methods: The estimates of age, sex, and country-specific incidence and mortality of 34 neoplasms in 54 African countries, were procured from GLOBOCAN 2020. Mortality-to-incidence ratio (MIR) was employed as a proxy indicator of 5-year survival rates, and the socioeconomic development of each country was measured using its human development index (HDI). We regressed age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and MIR on HDI using linear regression model to determine the relationship between cancer burden and HDI. Maps were generated for each cancer group for each country in Africa. The data about the cancer infrastructure of African countries were extracted from the WHO Cancer Country Profiles., Results: In Africa, an estimated 1.1 million new cases [95% uncertainty intervals (UIs) 1.0 - 1.3 million] and 711,429 [611,604 - 827,547] deaths occurred due to neoplasms in 2020. The ASIR was estimated to be 132.1/100,000, varying from 78.4/100,000 (Niger) to 212.5/100,000 (La Réunion) in 2020. The ASMR was 88.8/100,000 in Africa, ranging from 56.6/100,000 in the Republic of the Congo to 139.4/100,000 in Zimbabwe. The MIR of all cancer combined was 0.64 in Africa, varying from 0.49 in Mauritius to 0.78 in The Gambia. HDI had a significant negative correlation with MIR of all cancer groups combined and main cancer groups (prostate, breast, cervical and colorectal). HDI explained 75% of the variation in overall 5-year cancer survival (MIR). By 2040, the burden of all neoplasms combined is forecasted to increase to 2.1 million new cases and 1.4 million deaths in Africa., Conclusion: High cancer mortality rates in Africa demand a holistic approach toward cancer control and management, including, but not limited to, boosting cancer awareness, adopting primary and secondary prevention, mitigating risk factors, improving cancer infrastructure and timely treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharma, Aashima, Nanda, Fronterre, Sewagudde, Ssentongo, Yenney, Arhin, Oh, Amponsah-Manu and Ssentongo.)