Esophageal cancer (EC) is an aggressive malignancy and a major health burden documented as the sixth most common cause of cancer mortality worldwide (Bray et al., 2018). Over 80% of EC cases and deaths are reported in developing countries, where the esophageal squamous cell carcinoma (ESCC) subtype is more common, compared to the adenocarcinoma (EAC) subtype (Bray et al., 2018). EC has a peculiar geographical distribution, with high incidence rates reported in Asia and the African ESCC corridor (Abnet et al., 2017; McCormack et al., 2017; Bray et al., 2018). Malawi has the highest ESCC incidence rate globally for both men and women, followed by Kenya and Zimbabwe in Africa (Bray et al., 2018). In South Africa, ESCC is the 10th most common cancer for men and the 11th most common cancer for women (National Cancer Registry, 2019), and has the 10th highest incidence of ESCC in Africa (Bray et al., 2018). Incidence rates are, however, disproportionately higher in the Eastern Cape Province, where it is the most common cancer for men, and the second most common cancer for women (Somdyala et al., 2015). Due to a lack of ESCC early detection markers, late diagnosis and poor prognosis are the norm. Additionally, distinct ESCC molecular subtypes have not been identified, which could provide opportunities for targeted and novel therapies.

The African ESCC corridor (Figure 1), which spans from the eastern to the southern part of Africa is characterized by high incidence rates, young age at presentation, delayed presentation, as well as poor outcomes and survival (Van Loon et al., 2018; Asombang et al., 2019). Risk factors associated with ESCC in high-risk areas include tobacco smoking, alcohol consumption, polycyclic aromatic hydrocarbon exposure, poor diet, hot beverages, poor oral hygiene, microbiome, and genetic factors (Asombang et al., 2019; Chetwood et al., 2019; Simba et al., 2019; Simba, 2021).