Human T-Lymphotropic Virus Types I, II - HTLV I, II

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Adult T-cell leukemia/lymphoma (ATLL)
    • Fatigue, rash, lymphadenopathy, accompanied by lymphocytosis, hypercalcemia, and elevated lactate dehydrogenase (LDH)
  • Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paresis (HAM/TSP)
    • Muscle pain, stiffness, and weakness (myalgias and myopathy)
      • Changes in bowel and/or bladder function
      • Other neurological signs and symptoms including peripheral paresthesias and dysesthesias, hyperreflexia, tremor, deafness, changes in vision

Criteria for Diagnosis

ATLL subtypes and diagnostic criteria (Gonçalves, 2010)

Laboratory Testing

  • Required evaluation for ATLL (Shimoyama, 1991)
    • Peripheral blood smear – ATLL cells present
    • HTLV-I testing
      • HTLV-I and -II antibodies by enzyme immunoassay (EIA)/Western blot
        • Initial testing
        • HTLV-II antibodies significantly cross-react to HTLV-I antigens
          • Populations such as parenteral drug abusers infected with HTLV-II may test positive for HTLV-I antibodies due to antibody cross-reactivity
          • No evidence to suggest HTLV-II causes human disease
        • Asymptomatic patients with HTLV-I antibodies
          • May be infected and should not donate blood
          • Often do not have ATLL or TSP and may not develop ATLL, HAM, or TSP
        • Repeat Western blot testing for indeterminate results – 2 weeks and/or 3 months after initial testing
      • HTLV-I, II polymerase chain reaction (PCR) – use to resolve untypable HTLV Western blot results when there is a strong suspicion of HTLV infection
  • Cerebrospinal fluid (CSF) studies
    • Protein – increased
    • Cell differential – lymphocytic pleocytosis
    • HTLV antibodies – positive
    • Oligoclonal bands – positive
    • IgG index – high
  • Bone marrow exam – generally not required


  • If diagnosis not obtained by above, perform lesion biopsy (if present)
  • Immunophenotyping
    • Minimum testing should include CD3, CD4, CD7, CD8, and CD25
    • Most ATLL cells lack CD7, CD52 with diminished CD3
    • CD4+ T-cells express CD2, CD5, CD25, CD45RO, CD29
    • CD7 and CD26 negative and CD3 expression diminished

Imaging Studies

  • Computed tomography (CT) – recommend neck, thorax, abdomen, and pelvis to exclude extranodal disease
  • Upper gastrointestinal endoscopy
  • Central nervous system evaluation by CT/magnetic resonance imaging (MRI) if neurologic signs evident


  • Poor prognosis risk factors
    • Serum LDH elevated
    • Serum calcium elevated
    • Age ≥40
    • Three or more lesions
    • Additional – thrombocytopenia, eosinophilia, high IL5, p53 or p16 deletion

Differential Diagnosis

Human T-cell lymphotropic virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia/lymphoma (ATLL); tropical spastic paraparesis (TSP), a demyelinating neurological disorder; and HTLV-I-associated myelopathy (HAM).


  • Prevalence
    • 15-20 million infected with HTLV-I worldwide
    • Endemic in Japan, Caribbean countries, Papua New Guinea, and sub-Saharan Africa
  • Age
    • ATLL – mean 60 years
    • HAM/TSP – 40s-50s
  • Sex
    • ATLL – M>F
    • HAM/TSP – M<F
  • Transmission
    • Parenteral
    • Sexual
    • Breastfeeding
  • Lifetime risk of disease in presence of HTLV-I antibodies is low
    • ATLL – men have increased risk for progression compared to women
    • HAM/TSP – 0.5-4%


  • HTLV-I and HTLV-II are human type C retroviruses
    • Several subtypes exist that are geographically specific
      • HTLV-I – six subtypes (A-F)
    • Single-stranded RNA virus
  • Majority of human infections caused by HTLV-I
  • HTLV and AIDS​
    • HTLV-I does not cause AIDS
    • Antibodies of HTLV-I have no relationship to antibodies of HIV type I (HIV-I)
      • Antibodies to HTLV-I do not imply excess risk for AIDS
      • HTLV-I virus is only remotely related to HIV-I, the AIDS virus
      • HTLV-I and HTLV-II are transmitted similarly to HIV-I and HIV-II
      • Individuals with HTLV-I or HTLV-II may be coinfected with HIV due to common risk factors (eg, sexual contact, IV drug use)

Risk Factors

  • Cellular blood products – most efficient mode of transmission
  • Breast milk – 20% of children of infected mothers will also become infected
  • Sexual contact – associated with unprotected sex, multiple partners, presence of genital sores, sex exchanged for drugs or money
  • Sharing of contaminated needles and syringes (eg, IV drug use)
  • HTLV-I positive mother – perinatal transmission may occur
  • Poverty

Clinical Presentation

  • ATLL
    • 4 types – acute, chronic, smoldering, lymphoma
    • Acute ATLL most common
      • Rapidly fatal without treatment
      • Pulmonary complications, opportunistic infections, sepsis
      • Uncontrolled hypercalcemia may occur
  • TSP and HAM
    • Slowly progressive spastic paraparesis – disease is usually present 8-10 years before diagnosis
    • Prominent weakness of lower extremities with severe spasticity
      • Upper extremity weakness rare
      • Mild sensory impairment
      • Hyperreflexia is often present
      • Neuropathic pain is common in advanced stage
    • Bladder/bowel/sexual dysfunction later in disease – urinary tract infections, lithiasis, chronic pyelonephritis, chronic renal failure
    • Other associated diseases
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Human T-Lymphotropic Virus (HTLV) Types I/II Antibodies by ELISA with Reflex to HTLV-I/II Confirmation by Western Blot 0051164
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot


Assay should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues, and cellular and tissue-based products

Human T-Lymphotropic Virus Types I/II DNA, Qualitative Real-Time PCR 2003075
Method: Real-Time Polymerase Chain Reaction

Human T-Lymphotropic Virus Types I/II Antibodies, Western Blot 0020642
Method: Qualitative Western Blot


Assay should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues, and cellular and tissue-based products

Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry


Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009; 27(3): 453-9. PubMed

General References

Gonçalves DU, Proietti FA, Ribas JG, Araújo MG, Pinheiro SR, Guedes AC, Carneiro-Proietti AB. Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev. 2010; 23(3): 577-89. PubMed

Matutes E. Adult T-cell leukaemia/lymphoma. J Clin Pathol. 2007; 60(12): 1373-7. PubMed

Morrison BJ, Labo N, Miley WJ, Whitby D. Serodiagnosis for tumor viruses. Semin Oncol. 2015; 42(2): 191-206. PubMed

Qayyum S, Choi JK. Adult T-cell leukemia/lymphoma. Arch Pathol Lab Med. 2014; 138(2): 282-6. PubMed

Román GC. Tropical myelopathies. Handb Clin Neurol. 2014; 121: 1521-48. PubMed

Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991; 79(3): 428-37. PubMed

Taylor G. Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J Clin Pathol. 2007; 60(12): 1392-6. PubMed

Medical Reviewers

Last Update: September 2017