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

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 37 genomic, 27 proteomic, and 3 metabolic biomarkers identified

• Primary Outcome: Identification of 67 biomarkers associated with HTLV-1 disease progression

• Nnt Or Sensitivity: Proviral load showed limited sensitivity and specificity as standalone marker

• Confidence Interval: Not reported

Clinical Application

Requires specialized laboratory capabilities for omics-based testing; multiparametric panels may be complex to implement Limited direct relevance as HTLV-1 is uncommon in Australia, mainly affecting Indigenous populations in Central Australia and immigrants from endemic regions HTLV-1 infected individuals, particularly those in asymptomatic phase requiring risk stratification

Abstract

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.

References

1. 1.Leite, T., Abreu, M. E. S., Silva, A. A. R., Sebastião, R. A. S., Romão, L. A., Casseb, J., Assone, T., Leal, F. E., & Mateos, S. O. G. (2024). Molecular biomarkers associated with ATLL and HAM progression in HTLV-1 infection: a systematic review. Revista do Instituto de Medicina Tropical de Sao Paulo, 68, Article 030. https://doi.org/10.1590/S1678-9946202668030