Molecular biomarkers associated with ATLL and HAM progression in HTLV-1 infection: a systematic review

Resumen

Human T-lymphotropic virus type 1 (HTLV-1) infects approximately five to 10 million individuals worldwide, although only a minority develop severe outcomes such as adult T-cell leukemia/lymphoma (ATLL) or HTLV-1-associated myelopathy (HAM). Proviral load (PVL), while widely used, shows limited sensitivity and specificity, reinforcing the need for complementary biomarkers. Omics-based approaches have emerged as promising tools to improve risk prediction. We conducted a systematic review following PRISMA guidelines, searching PubMed, Web of Science, Virtual Health Library (BVS), and CAPES Periodicals databases for studies published between May 2020 and May 2025. Eligible studies included original observational designs investigating genomic, proteomic, and metabolic biomarkers associated with progression to ATLL or HAM. Methodological quality was assessed using tools from the National Heart, Lung, and Blood Institute (NHLBI). In total, 35 studies met the inclusion criteria, most conducted in Brazil, Japan, and Iran. A total of 67 biomarkers were identified: 37 genomic, 27 proteomic, and three metabolic with potential clinical applications in risk stratification, prognosis, and therapeutic monitoring of HTLV-1 infection. PVL remained the most frequently investigated marker but lacked predictive power in isolation. Additional candidates with strong potential included IFN-γ, CXCL10, Neopterin, AnxA1, and sTNFR2. This review highlights the potential of integrated multiparametric panels—combining PVL with omics-derived biomarkers—as a promising strategy to improve risk stratification, prognosis, and therapeutic monitoring in people living with HTLV-1 (PLHTLV-1). However, further longitudinal and clinically validated studies are needed to confirm their applicability and support their translation into early intervention strategies, particularly during the asymptomatic phase.