HTLV-1 and ATLL: Opportunities for Community-Informed Research in the United States

The Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 also causes inflammatory disorders, including HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. The estimated lifetime risks of ATLL and HAM/TSP in HTLV-1 carriers are 3-5% and 0.25-1.8%, respectively. Although there is uncertainty about other health effects of HTLV-1, a recent meta-analysis showed association between HTLV-1 and cardiovascular, cerebrovascular, and metabolic diseases, and a 57% increased risk of early mortality, in HTLV-1 carriers, independent of ATLL or HAM/TSP. Furthermore, emerging studies in endemic areas show that outcomes for common cancers, such as cervical cancer and lymphoma (non-ATLL) are inferior in HTLV-1 carriers compared to publicly reported data. Thus, the public health impact of HTLV-1 may be greater and more diverse than currently understood and the full spectrum and prevalence of HTLV-1-associated disorders need to be better investigated, in both endemic and non-endemic areas. Furthermore, the mechanisms by which HTLV-1 functions as a disease driver or modifier need to be studied. This review provides an outline of the prevalence and impact of HTLV-1 and associated disorders in the US, focused on - but not limited to - ATLL, with emphasis on education gaps and other social determinants of health that can affect the success of screening and prevention strategies, especially in immigrant communities at risk. We also discuss mechanisms by which HTLV-1 drives the pathogenesis of ATLL, and potential strategies for early diagnosis and intervention. Finally, we conclude by suggesting approaches to design and implement community-informed research initiatives in HTLV-1 and ATLL.