Lymphotropic Viruses EBV, KSHV and HTLV in Latin America: Epidemiology and Associated Malignancies. A Literature-Based Study by the RIAL-CYTED

Abstract

The Epstein–Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV) and human T-lymphotropic virus (HTLV-1) are lymphomagenic viruses with region-specific induced morbidity. The RIAL-CYTED aims to increase the knowledge of lymphoma in Latin America (LA), and, as such, we systematically analyzed the literature to better understand our risk for virus-induced lymphoma. We observed that high endemicity regions for certain lymphomas, e.g., Mexico and Peru, have a high incidence of EBV-positive lymphomas of T/NK cell origin. Peru also carries the highest frequency of EBV-positive classical Hodgkin lymphoma (HL) and EBV-positive diffuse large B cell lymphoma, not otherwise specified (NOS), than any other LA country. Adult T cell lymphoma is endemic to the North of Brazil and Chile. While only few cases of KSHV-positive lymphomas were found, in spite of the close correlation of Kaposi sarcoma and the prevalence of pathogenic types of KSHV. Both EBV-associated HL and Burkitt lymphoma mainly affect young children, unlike in developed countries, in which adolescents and young adults are the most affected, correlating with an early EBV seroconversion for LA population despite of lack of infectious mononucleosis symptoms. High endemicity of KSHV and HTLV infection was observed among Amerindian populations, with differences between Amazonian and Andean populations.

Estimating the global burden of Epstein–Barr virus-related cancers

“…It was in cultures of these tumour cells that EBV was discovered by electron microscopy (Epstein et al 1964). According to the WHO, three groups of BL exist: eBL, which overlaps with P. falciparum endemic areas; sporadic BL, which develops outside of P. falciparum endemic areas; and immunodeficiency-associated BL (further described below under "EBV-associated Immunosuppressive cancers") (Molyneux et al 2012;Chabay et al 2020). eBL is a prevalent childhood cancer in Equatorial Africa and Papua New Guinea and affects approximately 3-6 per 100,000 children under the age of 14, and between 81 and 100% of all cases are EBV-positive (Magrath 2012;Plummer et al 2016;Hammerl et al 2019).…”

“…eBL is a prevalent childhood cancer in Equatorial Africa and Papua New Guinea and affects approximately 3-6 per 100,000 children under the age of 14, and between 81 and 100% of all cases are EBV-positive (Magrath 2012;Plummer et al 2016;Hammerl et al 2019). In Latin America, EBV association frequencies are lower, occurring in 29-87% of BL cases with frequencies increasing with geographic latitude (Chabay et al 2020). Approximately 10-15% of sporadic BL cases are EBV-associated and a recent study referencing the GLOBOCAN 2018 database estimated that globally, around 6600 (55%) new cases of BL in 2018 were EBV-associated (Mawson and Majumdar 2017;de Martel et al 2020).…”

Plasma EBV DNA: A Promising Diagnostic Marker for Endemic Burkitt Lymphoma

“…Our analysis suggests that measurements of EBV copy number in plasma may be a promising diagnostic marker for endemic Burkitt lymphoma in Africa and BL occurring in other regions, such as Latin America ( 30 ), with high proportions of EBV(+) BL. These results warrant exploration in larger studies, which would further characterize the clinical scenarios that might benefit most for such plasma DNA assessments.…”

Virus-Driven Carcinogenesis

“…Clinico-epidemiologically, KS is classified into four types: classic indolent KS, endemic African KS, AIDS-associated KS, and iatrogenic KS. KSHV is consistently detected in all subtypes, suggesting that the pathogenesis is associated with epidemiological distribution and/or immunosuppression [ 247 , 248 ]. Although clinical KS shows a multistage disease process (patch, plaque, and nodular stages), the lesions may show regression [ 249 ].…”