Risk Factors for Malignant Progression to Adult-T-Cell Leukemia/Lymphoma in HTLV-1 Carriers: A Systematic Review of Cohort and Case-Control Studies

Objective: To systematically evaluate and synthesize the existing evidence from cohort and case-control studies to identify risk factors associated with malignant progression to ATLL in HTLV-1 carriers. Methods: A systematic search was conducted in September 2023 in the following databases: Pubmed, Scopus, Web of Science, Medline and Embase. Only case-control and cohort studies that assessed the risk factors for the malignant progression to ATLL among HTLV-1 carriers in the adult population were included. The risk of bias was assessed through the Newcastle-Ottawa Scale. Meta-analysis was not performed due to high statistical and methodological heterogeneity. Results: After conducting a systematic search, 8170 results were retrieved, of which 9 (7 case-control and 2 cohort studies) met the selection criteria. Seven of them were conducted in Japan and six had low risk of bias. Serum sIL-2R levels, proviral load (PVL), cigarette consumption, Scd30 and TNF-α-857T allele were associated with an increased risk of ATLL progression. Conclusion: PVL emerges as the foremost recommended biomarker for predicting progression in patients with HTLV-1 associated ATLL. Further studies with larger samples sizes, different populations, more rigorous statistical adjustments, and longer follow-up are warranted.