# Adult T-cell Leukemia/Lymphoma in French Guiana (1990-2019): Epidemiology, Clinical Features, and HTLV-1 Genetic Diversity in the Two Main Ethnic Populations

Jill-Léa Ramassamy, Patricia Tortevoye, Balthazar Ntab, Gabriel Carles, Jean-Pierre Droz, Pierre Couppié, Giovanni Begliomini, Jean-François Carod, N'detodji-Bill Wankpo, Karim Abdelmoumen, et al.

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Jill-Léa Ramassamy, Patricia Tortevoye, Balthazar Ntab, Gabriel Carles, Jean-Pierre Droz, et al. Adult T-cell Leukemia/Lymphoma in French Guiana (1990-2019): Epidemiology, Clinical Features, and HTLV-1 Genetic Diversity in the Two Main Ethnic Populations. 2025. pasteur-05125342

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1 Adult T-cell Leukemia/Lymphoma in French Guiana (1990–2019): Epidemiology,

2 Clinical Features, and HTLV-1 Genetic Diversity in the Two Main Ethnic Populations

3 Jill-Léa Ramassamy¹*, Patricia Tortevoye¹, Balthazar Ntab², Gabriel Carles³, Jean-Pierre

4 Droz⁴,⁷, Pierre Couppié⁵, Giovanni Begliomini¹, Jean-François Carod⁶, N'detodji-Bill

5 Wankpo⁷, Karim Abdelmoumen⁵,⁸, Philippe V. Afonso¹, Olivier Cassar¹, Antoine Talarmin⁹,

6 Olivier Hermine¹⁰, Loïc Epelboin¹¹,¹², Ambroise Marçais¹⁰, and Antoine Gessain¹

7 1) Institut Pasteur, Université de Paris-Cité, CNRS UMR 3569, Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes, F-75015 Paris, France

8 2) Département de l'Information Médicale, Centre Hospitalier de l'Ouest Guyanais, Franck Joly, Saint-Laurent-du-Maroni, French Guiana;

10 3) Service de Gynécologie-Obstétrique, Centre Hospitalier de l'Ouest Guyanais, Franck Joly, Saint-Laurent-du-Maroni, French Guiana;

13 4) Medical Oncology, Claude-Bernard Lyon-1 University, Lyon, France

14 5) Department of Dermatology, Cayenne Hospital, French Guiana, France

15 6) Laboratoire de biologie médicale, Centre hospitalier de l'ouest guyanais, Saint-Laurent-du-Maroni, Guyane.

17 7) Oncology Program, Centre Hospitalier de l'Ouest-Guyane, Saint-Laurent du Maroni, French Guiana, France

19 8) Department of Internal Medicine, University of la Réunion, Reunion Island, France

20 9) Transmission, Reservoir and Diversity of Pathogens Unit, Institut Pasteur, Les Abymes, France

22 10) Department of Hematology, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, INSERM UMR 1151 and CNRS, Institut Necker, Université Paris Cité, Paris, France.

25 11) Infectious and Tropical Diseases Unit, Cayenne Hospital and French Guiana University, French Guiana, France

27 12) Centre d'Investigation Clinique, Inserm 1424, UA17 Santé des Populations Amazoniennes, Cayenne Hospital, French Guiana, France

29 * Corresponding author: Dr Jill-Léa Ramassamy; jill.lea.ramassamy@pasteur.fr;

31 Unité EPVO, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France

32 Alternate corresponding author: Pr Antoine Gessain; antoine.gessain@pasteur.fr; Tel: (+33)

33 01 45 68 89 37

34 **Keywords:** Adult T-cell Leukemia/Lymphoma (ATL); Human T-lymphotropic virus type 1 (HTLV-1); French Guiana; Cancer epidemiology; South America; Ethnic health disparities;

37 Molecular phylogenetics.

38 **Conflict of interest:** The authors declare no potential conflicts of interest.

39 Running title: ATL Epidemiology in French Guiana Over 30 Years
40 ABSTRACT

41 Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive malignancy caused by human
42 T-cell leukemia virus type 1 (HTLV-1). French Guiana, located in northeastern South America,
43 is a region of high HTLV-1 endemicity with a multiethnic population. We conducted a
44 comprehensive 30-year study of ATL cases diagnosed between 1990 and 2019, capturing nearly
45 all confirmed ATL cases in the territory (n=137). The predominant subtypes were lymphoma
46 (58%) and acute ATL (36%). Striking ethnic disparities emerged: 69% of patients were
47 Maroons, and the median age at diagnosis was 43 years among Maroons versus 58 years among
48 Creoles. Survival outcomes were uniformly poor, with median overall survival of 2.7 months
49 for acute and 5.2 months for lymphoma ATL. In multivariate analysis, acute ATL subtype and
50 hepatosplenomegaly at diagnosis were independently associated with worse survival. Complete
51 HTLV-1 genome sequences were obtained for seven ATL cases and phylogenetic analysis of
52 complete genomes revealed strong ethnic clustering: all Creole strains belonged to the
53 Transcontinental subtype, while all Maroon strains belonged to the West African subtype.

54 Moreover, HTLV-1 prevalence in the general population was measured among 1,078 Creoles
55 tested in 1998, with a prevalence of 3.1%, markedly lower and occurring at older ages compared
56 to previously published data for the Maroon population.

57 Our findings highlight pronounced disparities in ATL epidemiology by ethnic group, and
58 emphasize the need for targeted prevention, early diagnosis, and improved care in high-risk
59 populations.
60 INTRODUCTION

61 Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy caused by human T-cell
62 leukemia virus type 1 (HTLV-1), a retrovirus infecting at least 10 million people worldwide
63 (1). It is considered the most oncogenic human virus (2). In Japan—the best-studied endemic
64 region—ATL develops in about 2–3% of infected women and 6–7% of infected men, the
65 highest incidence of any cancer linked to a viral infection (3). Outside Japan, large series of
66 ATL cases have been described in Brazil, Peru, and Jamaica (4–7). Despite HTLV-1 being
67 endemic in parts of the Caribbean, South America, and sub-Saharan Africa, ATL is likely
68 underdiagnosed and underreported in these regions. Clinical heterogeneity, rapid disease
69 progression, limited access to HTLV-1 testing, and lack of awareness among healthcare
70 professionals could contribute to underreporting, as seen in Brazil and many African settings
71 (4,8–10).

72 French Guiana, located in north-eastern South America with borders on Brazil and Suriname,
73 is a French overseas territory with high HTLV-1 endemicity. French Guiana's population is a
74 mosaic of cultures, each defining itself and its neighbours as distinct ethnic groups with their
75 own histories, languages and cultures (11). Its population has grown from 114,000 in 1990 to
76 nearly 290,000 by 2020. French Guiana is a recognized endemic area for HTLV-1 with some
77 of the highest prevalence rates reported in the Americas. Seroprevalence studies since the 1980s
78 have shown particularly high rates among the Maroon (or Businenge) population—descendants
79 of African slaves of the former Dutch Guiana, current Suriname, who settled in remote interior
80 regions—reaching up to 40% in adults in certain communities (12–14). While overall HTLV-1
81 prevalence has declined in more recent decades, notably among pregnant women (15),
82 significant disparities persist between ethnic groups, with consistently higher rates among
83 Maroon women compared to Creoles, Amerindians, Brazilians and those of European descent
84 (11,16).
This persistent viral burden poses a major risk for HTLV-1-associated diseases, notably ATL, 85 with cases showing high incidence and clinical diversity in French Guiana (17-19). 86

In this study, we aimed to provide a complete description of all ATL cases diagnosed in French 87 Guiana over a 30-year period (1990-2019), focusing on clinical and epidemiological 88 characteristics. We also report comparative data on HTLV-1 seroprevalence among the two 89 main populations affected by ATL (Maroon and Creole), and present a full molecular 90 characterization of HTLV-1 strains isolated from ATL patients in these groups. 91

## 92 METHODS

### 93 Data collection on ATL

We retrospectively reviewed all cases of ATL diagnosed between 1990 and 2019 in French 94 Guiana. Medical records were collected from the two main regional hospitals —Centre 95 Hospitalier de l'Ouest Guyanais (CHOG) in Saint-Laurent du Maroni and Centre Hospitalier 96 de Cayenne (CHC)—as well as from patients referred to mainland France, notably Necker 97 Hospital in Paris, for diagnostic confirmation or advanced treatment. To ensure diagnostic 98 accuracy and optimal classification, three authors (AG, PT, JPD) reviewed and verified records 99 annually over the 30-year study period, in close collaboration with local clinicians (oncologists, 100 hematologists, dermatologists, and internists). 101

ATL diagnosis required a compatible clinical presentation and confirmed HTLV-1 infection by 102 Western blot and/or HTLV-1-specific PCR. ATL subtype classification followed the 103 Shimoyama criteria (20). 104

Patients' data base was anonymized. Demographic data collected were date of birth, age, 105 gender, birth and living place, language (allowing to indirectly define cultural group), Human 106 Immunodeficiency Virus (HIV) serology results, date of diagnosis, and date of last follow-up 107 and status. ATL characteristics data included liver, spleen, lymph nodes enlargements, and skin 108 lesions, calcemia, lactate dehydrogenase (LDH) level, gut invasion by *Strongyloides* 109 stercoralis, complete blood count (CBC), blood cytology (search of atypical lymphocytes), and 110
treatment. When available, immunophenotyping of peripheral blood and/or tissue samples, T-cell receptor (TCR) analysis, and HTLV-1 clonality assessments were performed by Southern blot or Next Generation Sequencing (21).

## Epidemiological analysis/methods

For patients with incomplete diagnosis dates, January 15 was assigned when only the year was available, and the 15th of the month when only the month was known. Patients discharged against medical advice were presumed deceased for survival analysis. The database was locked on 01/01/2020. Age at diagnosis between patient groups was compared using the Mann-Whitney U test. Median survival time (MST) and overall survival (OS) were estimated using the Kaplan-Meier method; survival distributions were compared using the log-rank test. Variables showing significant associations in univariate analyses (*p*<0.05) and those considered clinically relevant were included in the multivariate Cox proportional hazards regression model. Multiple imputations were performed to replace missing values for the variable “LDH”, using the multivariable imputation by chained equations (MICE) method. Statistical analyses were performed using Stata 15.0 (RRID:SCR_012763, Stata Corporation, College Station, TX).

## Determination of HTLV-1 prevalence per ethnic group.

To assess differences in HTLV-1 exposure by ethnicity, we analyzed anonymized data from a 1998 sero-epidemiological survey of 1,028 Creole individuals carried out by the Institut Pasteur de la Guyane, originally designed for arbovirus or malaria investigations. Serum samples were initially screened by ELISA, and positive results were tested by Western blot confirmatory assay, following manufacturer guidelines. These results were compared with contemporaneous published data from a similar survey conducted among the Maroon population (13). HTLV-1 prevalence and 95% confidence intervals (CIs) were calculated and compared between groups using the χ² test or Fisher exact test, accordingly.
135 **Whole genome sequencing of HTLV-1 from ATL patients.**

136 High molecular weight DNA from peripheral blood buffy coats underwent four PCR series with
137 primers LTR-*gag* (F1), *pro-pol* (F2), *pol-env* (F3), and Px-LTR (F4) targeting conserved major
138 HTLV-1 subtypes (22). The resulting amplicons sizes were: LTR-*gag*, 2,136-bp; *pro-pol*,
139 2,769-bp; *pol-env*, 2,078-bp and Px-LTR, 2,905-bp. Amplification used a PIKO thermocycler
140 (Ozyme, Saint Quentin-en-Yvelines, France). PCR products (45 µl) were sent to Eurofins
141 Genomics (Eurofins Genomics, Cologne, Germany) for purification and sequencing. The
142 fragments were sequenced with 18 primers pairs, and ClustalW (RRID:SCR_017277),
143 MacVector 18.6.1 software (RRID:SCR_015700, Oxford Molecular) aligned forward and
144 reverse sequences of each segment to generate the full genome.

145 **Phylogenetic analyses**

146 For the LTR and concatenated *gag-pol-env-tax* genes analyses, sequences were aligned using
147 the DAMBE program (version 4.2.13). The final alignment was submitted to the Modeltest
148 program (version 3.6) and the best model was selected according to the Akaike information
149 criterion. This model was applied in PAUP program (RRID:SCR_014931, version 4.0b10) for
150 Neighbor-Joining (NJ) tree inference, validated by Maximum Likelihood method using
151 SEAVIEW (v5) with clade robustness estimated by approximate likelihood-ratio test (aLRT).

152 **RESULTS**

153 **ATL cases report**

154 From 1990 to 2019, 145 ATL cases were identified in French Guiana. After exclusion of eight
155 cases (one duplicate, one lacking clinical data, and six unconfirmed cases), 137 confirmed ATL
156 cases were included in the analysis. Initial diagnoses were made at the Centre Hospitalier de
157 l'Ouest Guyanais (CHOG, 64 cases), Centre Hospitalier de Cayenne (CHC, 62 cases), and
158 Centre Hospitalier de Kourou (CHK, 2 cases). An additional ten cases were diagnosed in other
159 hospitals (mainland France, Martinique, Suriname and Netherlands) but managed locally
160 (Figure 1). Annual incidence ranged from 1 to 10 cases, with a median of 4 per year. According
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to Shimoyama's classification, 80 cases (58%) were of the lymphoma subtype, 49 (36%) acute, 5 (4%) smoldering, and 4 (2%) chronic (Supplemental Figure 1).

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## Demographic and Ethnic Distribution

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Of the 137 patients, 65 were male (47%) and 72 female (53%), with a median age at diagnosis of 48 years (range: 18-86). Age did not significantly differ by gender (median 47.2 vs. 50.8 years; *p* = 0.18). The majority were Maroons (n = 94, 69%), followed by Creoles (n = 40, 29%), and others or unknown ethnicity (n = 3, 2%). Among the Maroon group, 61% were born in Suriname, 14% in French Guiana, and 26% had unspecified birthplace. Other countries of origin included Haiti, Martinique, Guadeloupe, Brazil, Guyana, and Ivory Coast (Figure 1). The median age at diagnosis was significantly lower in Maroon than in Creoles (43 vs. 58 years, *p* < 0.001) (Figure 2A). The male-to-female ratio was 0.5 in Maroons and 1.1 in Creoles (*p* = 0.07). No significant differences were observed in ATL subtype distribution by age, gender, or ethnicity (Supplemental Table 1).

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Familial ATL was identified in eleven patients (8%) from five families—three Maroon and two Creole—including mostly sibling clusters, as well as one mother-child pair and one grand-mother-grandsons cluster.

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## Clinical Features and Co-Infections

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Clinical characteristics at ATL diagnosis are summarized in Table 3. Some clinical data were incomplete, particularly for cases diagnosed in the earlier decades. Lymphadenopathy was the most frequent clinical finding, reported in 82% of patients. Hepatosplenomegaly was present in 33% of cases, and 23% presented with ATL-specific cutaneous lesions. Elevated LDH levels were observed in 57% and hypercalcemia was documented in 50% of patients respectively. HIV co-infection was identified in 8 patients (5.8%). Strongyloidiasis at the time of ATL diagnosis was confirmed in 36 patients (26%). In addition, 9 patients had a prior history of severe *Strongyloides stercoralis* hyperinfection requiring urgent medical intervention. HTLV-

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1 clonality was assessed in twenty patient samples, all of which demonstrated monoclonal proliferation.

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Immunophenotyping was performed in 101 patients, using samples obtained primarily from lymph nodes, peripheral blood, skin biopsies and other tissues. The neoplastic T-cell proliferation typically expressed a CD3+, CD4+, CD7-, CD25+ immunophenotype. In five cases, a dual-positive CD4+/CD8+ phenotype was observed.

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## Treatment

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Among 137 patients, 88 (64%) received treatment, 35 (26%) did not, and treatment data were unavailable for 14 (10%). Treatment regimens included chemotherapy alone, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in 18% of cases, CHOP combined with AZT/IFN (zidovudine and interferon alpha) in 33%, and AZT/IFN alone in 11%. Overall, 45% received AZT/IFN during their treatment course. Only two patients underwent Allogeneic hematopoietic stem cell transplantation (HSCT) at Necker Hospital, in mainland France.

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## Survival analyses

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Survival data were available for 110 patients, with 78 confirmed and 21 estimated dates of death. Survival analyses yielded similar results whether restricted to confirmed dates or including both confirmed and estimated dates. For consistency, only confirmed dates of death were used in the analyses presented in this article. Six patients were lost to follow-up immediately after diagnosis and were excluded from survival analysis. Median survival times (MST) were 2.7 months (95% CI: 1.5-4) for acute ATL and 5.2 months (95% CI: 4-10) for lymphoma ATL. The 4-year overall survival (OS) rates were 6% and 17%, respectively. No significant difference in survival was observed by gender, age group, or ethnic background. However, in the univariate analysis, poor prognostic indicators included elevated LDH levels, hypercalcemia, and hepatosplenomegaly at diagnosis (Figure 3). In multivariate Cox analysis, acute ATL subtype (hazard ratio [HR] 1.83; 95% CI, 1.20-2.76; *p* = 0.004) and
hepatosplenomegaly at diagnosis (HR 1.87; 95% CI, 1.23-2.82; *p* = 0.003) were independently associated with poorer survival.

## Temporal and Epidemiological Trends

The number of ATL diagnoses increased over the study period. While the acute subtype was predominant in the 1990s (49%), the lymphoma subtype became the most common in the 2000s (70%) and 2010s (67%) (*p* = 0.03, Fisher's exact test). No significant temporal trends were observed in age at diagnosis, gender ratio, or ethnic group distribution (Supplemental Table 2). Survival outcomes did not improve over time. Although a trend for higher survival appeared during the 2000-2009 period. This finding is likely biased by a higher proportion of patients lost to follow-up in that decade (28%) (Figure 3).

## The epidemiology of HTLV-1 infection differs between Creoles and Maroons.

HTLV-1 prevalence among 1,078 Creoles tested in 1998 was 3.1% (95% CI: 2.2-4.3), increasing with age - 12% in individuals over 50, and none under 20. In contrast, in a contemporaneous survey from 1995 of 1,217 Maroons in Maripasoula, a city on the Maroni River banks bordering French Guiana and Suriname, HTLV-1 prevalence was significantly higher, at 8.1% (95% CI: 6.7-9.7; *p* < 0.001), with infection present from childhood (1.2% under 10 years) and peaking at 39% in those over 50 years (13) (Figure 2B).

## Molecular characterization and phylogeny of HTLV-1 genotype in ATL Patients by Ethnic Group

To further explore the molecular diversity of HTLV-1 strains circulating in French Guiana, we sequenced seven new complete HTLV-1 genomes (~9,040 bp) and included one previously published sequence (PH1209, accession MN781154). Of the eight sequences, five originated from Maroon ATL patients (PH561, PH1209, PH1210, PH1503, and PH1505), and three from Creole ATL patients: two from French Guiana (PH489 and PH1040) and one from Martinique (PH1002). GenBank accession numbers correspond to the new complete sequences obtained from ATL patients in French Guiana (Number form W to XX). Demographic and clinical data
for these cases are provided in Supplemental Table 3. Phylogenetic analysis revealed two distinct HTLV-1 subtypes associated with ethnic background. All strains from Creole patients clustered within the HTLV-1a-Transcontinental (HTLV-1a-TC) subtype, while those from Maroon patients belonged to the HTLV-1a-West African (HTLV-1a-WA) subtype. These results are consistent with earlier partial gene analyses and confirm ethnic-specific lineage patterns at the whole-genome level. Viral genome lengths ranged from 8,778 to 9,039 bp, with a shorter sequence for PH1210 showing a substantial deletion resulting in the absence of tax, rex, and hbz open reading frames. All other genomes encoded the expected viral proteins (gag, pro, pol, env, tax, p8/p12, p13, p30, and hbz), with the exception of PH1505, which harboured a premature stop codon in tax—a type of mutation often observed in ATL-associated strains (23). Despite some nucleotide variability, Tax protein sequences were conserved across all strains, and only one strain-specific mutation was observed in HBZ among Maroon sequences. Phylogenetic analysis based on the LTR regions (data not shown) and on the concatenated gag, pol, env, and tax genes (preserving the PH1210 deletion) confirmed clear clustering by ethnic background (Figure 4). PH1210 exhibited an extended branch length due to its deletion but remained within the HTLV-1a-WA clade.

## DISCUSSION

In this study, we conducted a comprehensive assessment of the epidemiological and clinical characteristics of ATL in French Guiana over a 30-year period. French Guiana is a region of high HTLV-1 endemicity in northeastern South America, with a unique multiethnic population and universal healthcare coverage. We believe our dataset includes the vast majority of ATL cases diagnosed in this territory during this time period, thanks to the proactive and systematic collection of clinical information from the region's main hospitals each year. Unlike many other HTLV-1 endemic areas, French Guiana has had local access to confirmatory HTLV-1 serologic testing since the 1990s, and benefits from France's universal healthcare system, which ensures that medical care is provided free of charge to patients. These conditions were likely to facilitate
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timely diagnosis and reduced underreporting, although they may also have led to a relative
overrepresentation of patients from neighbouring Suriname, particularly among the Maroon
population.

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Direct comparisons between our findings and those from other HTLV-1 endemic areas,
particularly in South America, are challenging. Most published series are hospital-based, and
often originate from specialized departments (e.g., dermatology, hematology, or pathology),
and HTLV-1 confirmation is not always performed systematically. As a result, these data may
be subject to multiple sources of bias and may not accurately reflect the true epidemiological
landscape at the regional or national level. Furthermore, it is likely that ATL remains
substantially underreported in many of these countries, as has been recently demonstrated in
Brazil. In Brazil, the estimated annual ATL incidence based on HTLV-1 prevalence modelling
is approximately 800 cases, whereas fewer than 20 cases per year are reported through national
cancer registries Brazil (9). In contrast, our dataset is one of the few to cover an entire territory
over three decades, strengthening its representativeness and the reliability of temporal and
interethnic comparisons.

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Why do ATL patterns differ between Creole and Maroon populations in French Guiana?

A striking finding of this study is the overrepresentation of Maroon individuals among ATL
cases: they accounted for 69% of all diagnosed case. While the exact proportion of Maroons
in the general population is uncertain due to the absence of ethnic data in French census records,
estimates suggest they represent approximately 20-30% of the population. However, this
comparison must be interpreted with caution due to several sources of bias. First, many Maroon
patients in our study were born in neighbouring Suriname and may not be included in official
French Guiana census data. Additionally, available population estimates may not fully reflect
the size and distribution of ethnic groups across the territory. Despite these limitations, the
disproportionately high burden of ATL among Maroons has been consistently reported in
French Guiana since the earliest case reports (17) and was also confirmed in a prospective
cohort of HTLV-1-infected women in the western part of the territory (18). Epidemiological studies have shown significantly higher HTLV-1 prevalence in young Maroon individuals (11,13), a pattern confirmed by our findings, which demonstrate consistently elevated age-specific prevalence compared to Creole individuals. Given that ATL risk increases with longer duration of HTLV-1 infection and is strongly associated with mother-to-child transmission (MTCT) (24,25), it is plausible that MTCT may contribute to the elevated ATL incidence in the Maroon population, —possibly linked to longer breastfeeding practices. Additional contributing factors may include genetic susceptibility—Maroons represent a relatively genetically distinct group (26)—as well as environmental exposure, coinfections, nutrition, or socio-cultural practices that may affect both HTLV-1 transmission dynamics and ATL progression. Of note, genome-wide data indicate that Maroons exhibit the highest proportion (98%) of African ancestry among populations of African descent in the Americas, reflecting their relative genetic isolation since the establishment of Maroon communities (26).

Estimating the overall incidence of ATL in French Guiana present significant challenges, particularly due to the territory's complex ethnic composition and the absence of ethnicity data in national census records, which is prohibited under French legislation. Our study, which likely includes the vast majority of ATL cases diagnosed in the region between 1990 and 2019, allows for a crude estimation of incidence in the general population at approximately 2.3 cases per 100,000 person-years (137 cases over an average population of 200,000 across 30 years). When calculated by decade using estimated average population sizes of 134,000, 194,000, and 264,000 for 1990–1999, 2000–2009, and 2010–2019 respectively (27), the corresponding crude annual incidence rates were approximately 2.9, 2.1, and 2.2 per 100,000 population. However, these figures are of limited interpretive value, as most of the ATL patients originated from neighboring Suriname.

A more informative approach would be to assess incidence within the two most affected subpopulations. For Creole individuals, incidence could be roughly estimated at 1.66 per
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100,000 per year (approximately 40 cases over an estimated 80,000 individuals over 30 years).

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In contrast, incidence estimates among Maroons are more complex: of the 94 ATL cases identified, 58 patients were born in Suriname. However, as mentioned earlier, the Maroon population is historically and culturally distributed across both sides of the Maroni River, spanning both French Guiana and Suriname, making accurate population-based incidence calculations problematic in the absence of cross-border demographic and HTLV-1 carrier estimates stratified by origin.

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Another important finding of our study is the marked difference in median age at ATL diagnosis between Creole and Maroon patients, 58 years vs. 43 years respectively. The age distribution observed in Creoles patients is consistent with reports from other Caribbean settings, including Martinique, Jamaica, and Caribbean diaspora in the United States (28–30). In contrast, the earlier onset observed in Maroons is notable and raises questions about underlying determinants. To our knowledge, no robust studies have yet examined whether genetic factors could contribute to earlier onset of HTLV-1-associated diseases in specific populations.

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However, relatively young median ages at diagnosis have also been reported in other endemic regions. In South America, Caribbean nations, and among Caribbean diaspora in the U.S., median ages range from 54 to 58 years (7,29–32). A few cases in children and young adults have also been reported, particularly in Brazil (33) Even younger median ages have been observed in certain non-Caribbean settings: a recent South African series of 31 ATL cases (including 10 HIV coinfections) reported a median age of 37 years (10), while a Romanian series of 20 cases reported a median age of 40 years (34). However, Japan presents a clear exception. The national Japanese ATL registry has reported a median diagnosis age of 69 in recent decades—nearly two decades older than in most other endemic areas (35–38). This represents a notable shift from the 1980s–1990s, when the median age was approximately 58–60 years. While this trend may reflect broader demographic aging, improved general health, or evolving patterns of HTLV-1 exposure such as breastfeeding prevention for HTLV-1 positive

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342 women (38), its underlying causes remain unclear. Comparable temporal trends have not been
343 established in other endemic areas due to the absence of long-term epidemiologic data outside
344 Japan.

345 Several factors may contribute to the younger age at diagnosis observed in French Guiana and
346 other non-Japanese settings. These include a higher burden of coinfections such as
347 *Strongyloides stercoralis* (SS), which has been associated with clonal expansion of HTLV-1-
348 infected cells and earlier ATL onset; socio-cultural practices such as prolonged breastfeeding
349 that increase the likelihood of mother-to-child transmission; nutritional factors; and potential
350 genetic susceptibility (3). In Martinique, ATL patients co-infected with SS had a significantly
351 lower median age at diagnosis (39 vs. 70 years) (39). In our study, although eight ATL patients
352 were diagnosed with severe SS infection, no significant association was found between SS
353 coinfection and age at diagnosis, likely due to the small sample size. Moreover, SS prevalence
354 at diagnosis did not differ between Creole and Maroon patients.

355 **Why is the prognosis of ATL so poor in French Guiana?** Survival outcomes for ATL in
356 French Guiana were alarmingly poor, with an overall median survival time (MST) of 4.7
357 months—3.2 months for the acute subtype and 6.1 months for the lymphoma subtype. These
358 results are consistent with those reported in Caribbean cohorts, such as Jamaica (MSTs of 3 and
359 5 months for acute and lymphoma types, respectively, in the 1990s) and Martinique (3 and 8
360 months, respectively), where survival outcomes remain similarly dismal (6,28). Poor outcomes
361 have also been reported in Central and South America (4.3 and 7.9 months, respectively),
362 notably in Brazil (MSTs ranging from 2.5 to 11 months depending on subtype and study),
363 Colombia (5 months), Peru (7 months), but also in Romania (6.4 months) (4,5,7,31,34,40,41).
364 In contrast, survival appears somewhat better in Japan (MST of 8–13 months depending on
365 subtype) and in large registry-based studies in the United States (29,30,36). These variations
366 are likely to reflect differences in access to early diagnosis, treatment availability, and
367 potentially the burden of co-infections and comorbidities. It remains unclear however whether
368 HTLV-1 genotype could be associated to poor outcome ATL forms. Poor prognostic factors in 369 our study were consistent with other reports, including acute subtype, hypercalcemia, 370 hepatosplenomegaly, and elevated LDH levels (19,34,37,41,42).

371 In French Guiana, several factors may contribute to poor outcome. Late diagnosis, as observed 372 for other cancers in the region, is likely a major contributor, and may also explain the over- 373 representation of aggressive subtypes such as acute and lymphoma ATL (43). In addition, lack 374 of access to treatment or refusal of therapy, as well as frequent recourse to traditional 375 medicine—especially within the Maroon (NM) community—appear to be a key barrier to care 376 (44,45). In our study 26% of patients received no treatment, and 10% were lost to follow-up 377 immediately after diagnosis. Given the sociocultural and geographic ties of the Maroon 378 population between French Guiana and neighboring Suriname, it is plausible that some patients 379 returned to Suriname or migrated to the Netherlands for treatment, resulting in incomplete 380 follow-up data (46). However, a significant number of patients declined treatment and were 381 discharged against medical advice likely leading to an underestimation of the true case fatality 382 rate. Therefore, actual survival times may be even shorter than reported.

383 Alarmingly, our results indicate no clear improvement in survival outcomes over the past three 384 decades, despite evolving therapeutic strategies. Poor outcomes among ATL patients treated 385 with AZT/IFN has been highlighted in a previous multicenter study (47). A major limitation of 386 our study is the lack of detailed treatment data, which limited our capacity to assess treatment 387 effectiveness or the evaluation of identify prognostic biomarkers. Additionally, advanced 388 diagnostic techniques (e.g., flow cytometry, and clonality studies) were not systematically 389 applied over the entire study period.

390 What insights does HTLV-1 whole genome analysis provide? HTLV-1 whole genome could 391 be obtained for seven ATL patients from our series. We observed a clear difference in HTLV- 392 1 clades between the two main populations: the Cosmopolitan transcontinental subtype (a-TC) 393 predominates among Creoles, while the West African subtype (a-WA) is more frequent among
394 Maroons. While differences in viral genotype have been associated with disease phenotypes in
395 other contexts—such as a differential risk of HTLV-1-Associated Myelopathy (HAM)/Tropical
396 Spastic Paraparesis (TSP) with Japanese vs. transcontinental tax subgroups (48), or a potential
397 association between HTLV-1c and bronchiectasis in Indigenous Australians (49,50)—our
398 comparative molecular analysis of full-length sequences did not reveal clear genotype-related
399 differences in leukemogenic potential.

400 Finally, the systematic collection of ATL cases over three decades provides a rare and valuable
401 overview of the burden of this HTLV-1-associated malignancy in French Guiana. Despite local
402 diagnostic capacity and universal healthcare coverage in theory, survival outcomes remain
403 dismal, reflecting the lack of effective treatments and persistent inequalities in access to timely
404 and appropriate care, particularly among vulnerable and marginalized populations. Our findings
405 underscore the urgent need for improved therapeutic options and adapted prevention strategies,
406 particularly breastfeeding alternatives for HTLV-1-infected women, tailored to the unique
407 socio-demographic and geographic context of French Guiana.

408 FUNDINGS

409 JLR received financial support from the European Union (FOOD/2016/379-660). This study
410 received funding from the CNRS (UMR 3569) (AG); the Institut Pasteur, France (AG), and
411 through the “Investissement d’Avenir” as part of a French “Laboratoire d’Excellence” (LabEx)
412 research program: Integrative Biology of Emerging Infectious Diseases (ANR10-LBX-62
413 IBEID) (AG).

414 ACKNOWLEDGMENT

415 We gratefully acknowledge the clinical and laboratory teams at both Centre Hospitalier de
416 Cayenne (CHC) and Centre Hospitalier de l'Ouest Guyanais (CHOG) for their invaluable
417 support throughout this study. We also thank the staff of the Service de Protection Maternelle
418 et Infantile of the Direction Départementale des Affaires Sanitaires et Sociales de Guyane, as
419 well as the Gynecology-Obstetrics Department of CHOG, for their assistance with data
420 collection and patient follow-up.

421 ChatGPT-4 was used to edit the text of the article to improve readability and language.

422 ETHICS STATEMENT

423 This study was initially authorized by the Commission Nationale de l'Informatique et des
424 Libertés and the Comité de Protection des Personnes dans la Recherche Biomedicale (Necker
425 Hospital and Sud-Ouest et Outremer III). It was later approved by the ethics committee and
426 institutional review board of French Guiana (F20211125135043). The ethical committee
427 waived the need for written informed consent because of the retrospective nature of the study
428 and anonymous data collection. The hospitals databases were declared according to the
429 reference methodology MR-004 and the European General Data Protection (GRPD) guidelines.

430 DATA AVAILABILITY STATEMENT

431 The individual-level clinical data generated and analyzed in this study are not publicly available
432 due to privacy and ethical restrictions related to medical and personal information. The
433 complete HTLV-1 genome sequences generated during this study have been deposited in
434 GenBank under accession numbers [under submission], and are publicly available.
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582

583

584
<caption>Table 1. Demographic description of ATL cases</caption>

587

<table><thead><tr><th rowspan="2"></th><th colspan="2">ATL cases</th><th colspan="2">Age at diagnosis</th></tr><tr><th>N</th><th>%</th><th>Median (range)</th><th>p-value</th></tr></thead><tbody><tr><td>Total</td><td>137</td><td>100%</td><td>48 (18-86)</td><td></td></tr><tr><td>Year of diagnosis</td><td></td><td></td><td></td><td></td></tr><tr><td>1990-1999</td><td>39</td><td>28.5%</td><td>47.8 (21-86)</td><td>NS</td></tr><tr><td>2000-2009</td><td>40</td><td>29.2%</td><td>49 (21-82)</td><td></td></tr><tr><td>2010-2019</td><td>58</td><td>42.3%</td><td>49.5 (18-82)</td><td></td></tr><tr><td>Gender</td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>65</td><td>47.4%</td><td>43 (18-82)</td><td>NS</td></tr><tr><td>Female</td><td>72</td><td>52.6%</td><td>50.5 (21-86)</td><td></td></tr><tr><td>Ethnic group</td><td></td><td></td><td></td><td></td></tr><tr><td>Maroon</td><td>94</td><td>68.6%</td><td>43 (18-86)</td><td>&lt;0.001***</td></tr><tr><td>Creole</td><td>40</td><td>29.2%</td><td>58 (35-82)</td><td></td></tr><tr><td>Else or N/A</td><td>3</td><td>2.2%</td><td>75 (31-78)</td><td></td></tr><tr><td>ATL subtypes</td><td></td><td></td><td></td><td></td></tr><tr><td>Lymphoma</td><td>80</td><td>58.4%</td><td>50 (18-86)</td><td>0.03*</td></tr><tr><td>Acute</td><td>49</td><td>35.8%</td><td>42 (21-82)</td><td></td></tr><tr><td>Smoldering</td><td>5</td><td>3.6%</td><td>54 (27-79)</td><td></td></tr><tr><td>Chronic</td><td>3</td><td>2.2%</td><td>25 (21-28)</td><td></td></tr><tr><td>HIV infection</td><td></td><td></td><td></td><td></td></tr><tr><td>Negative</td><td>88</td><td>64.2%</td><td>47 (18-82)</td><td>NS</td></tr><tr><td>HIV positive</td><td>8</td><td>5.8%</td><td>49.5 (35-69)</td><td></td></tr><tr><td>N/A</td><td>41</td><td>29.9%</td><td>52 (23-86)</td><td></td></tr></tbody></table>

588 Statistically significant differences in age at diagnosis are indicated in bold. ATL Adult T-cell
589 Leukemia/Lymphoma; HIV Human Immunodeficiency; Virus N/A not available; NS not
590 significant; * p<0.05; **p<0.01, ***p<0.001.

591

592
<table><caption>Table 2. Clinical Characteristic of ATL patients at diagnosis and treatment per ATL subtypes</caption><thead><tr><th></th><th>Overall</th><th>Lymphoma Acute</th><th>Smoldering</th><th>Chronic</th></tr></thead><tbody><tr><td>N ATL</td><td>137</td><td>80</td><td>49</td><td>5</td><td>3</td></tr><tr><td>Lymphadenopathies</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>112 (82%)</td><td>69 (86%)</td><td>40 (82%)</td><td>2 (40%)</td><td>1 (33%)</td></tr><tr><td>Hepatosplenomegaly</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>45 (33%)</td><td>23 (29%)</td><td>22 (45%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Unknown (%)</td><td>2 (1%)</td><td>2 (3%)</td><td>0 (0%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Skin lesions</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>32 (23%)</td><td>15 (19%)</td><td>13 (27%)</td><td>3 (60%)</td><td>1 (33%)</td></tr><tr><td>Unknown (%)</td><td>3 (2%)</td><td>2 (3%)</td><td>1 (2%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Hypercalcemia</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>68 (50%)</td><td>39 (49%)</td><td>29 (59%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Unknown (%)</td><td>1 (1%)</td><td>1 (1%)</td><td>0 (0%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>High LDH</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>78 (57%)</td><td>46 (58%)</td><td>31 (63%)</td><td>0 (0%)</td><td>1 (33%)</td></tr><tr><td>Unknown (%)</td><td>41 (30%)</td><td>25 (31%)</td><td>14 (29%)</td><td>1 (20%)</td><td>1 (33%)</td></tr><tr><td>Hyperlymphocytosis</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>52 (38%)</td><td>0 (0%)</td><td>46 (94%)</td><td>3 (60%)</td><td>3 (100%)</td></tr><tr><td>Unknown (%)</td><td>20 (15%)</td><td>16 (20%)</td><td>3 (6%)</td><td>1 (20%)</td><td>0 (0%)</td></tr><tr><td>Strongyloides infection</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Present (%)</td><td>36 (26%)</td><td>21 (26%)</td><td>14 (29%)</td><td>0 (0%)</td><td>1 (33%)</td></tr><tr><td>Unknown (%)</td><td>48 (35%)</td><td>29 (36%)</td><td>17 (35%)</td><td>2 (40%)</td><td>0 (0%)</td></tr><tr><td>Treatment</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>No treatment</td><td>35 (26%)</td><td>16 (20%)</td><td>15 (31%)</td><td>3 (60%)</td><td>1 (33%)</td></tr><tr><td>CHOP only</td><td>25 (18%)</td><td>15 (19%)</td><td>9 (18%)</td><td>0 (0%)</td><td>1 (33%)</td></tr><tr><td>AZT/IFN only</td><td>15 (11%)</td><td>9 (11%)</td><td>4 (8%)</td><td>1 (20%)</td><td>1 (33%)</td></tr><tr><td>CHOP+AZT/IFN</td><td>45 (33%)</td><td>31 (39%)</td><td>14 (29%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Allo-HSCT</td><td>2 (1%)</td><td>1 (1%)</td><td>1 (2%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td>Unknown</td><td>15 (11%)</td><td>8 (10%)</td><td>6 (12%)</td><td>1 (20%)</td><td>0 (0%)</td></tr></tbody></table>
597

**Figure 1. Geographic distribution of hospital diagnosis for ATL treated in French Guiana over the past 30 years.**

598

599

(A) Location of hospitals where ATL from French Guiana cases were initially diagnosed. (B) Country of birth of ATL patients. * Martinique (1), Haiti (3), Guadeloupe (1), unspecified (1).

600

601

**Figure 2. Age and ethnic distribution of ATL cases and HTLV-1 prevalence in French Guiana.**

602

603

(A) Age at diagnosis of ATL cases, stratified by ethnic group (Maroon and Creole). Numbers within the figure indicate the total number of cases and the median age (and range) at diagnosis for each group. (B) HTLV-1 prevalence by age and ethnic group among 1,078 Creole individuals (current study) and 1,217 Maroon individuals (from previously published data).

604

605

606

607

Numbers shown in the figure correspond to the number of HTLV-1-infected individuals over the total tested (n/N), with associated prevalence and 95% confidence intervals (95%CI). Error bars represent 95% Wilson confidence intervals.

608

609

610

**Figure 3. Kaplan-Meier survival curves of ATL cases by clinical and demographic characteristics.**

611

612

Survival is shown according to: (A) ATL subtype, (B) decade of diagnosis, (C) ethnic group, and clinical parameters at diagnosis—(D) LDH level, (E) presence of hypercalcemia, and (F) hepatosplenomegaly. Log-rank p-values for the comparison of survival functions are shown for each variable. Clinical indicators significantly associated with poorer survival are highlighted in red (p < 0.05). * p<0.05; **p<0.01, ***p<0.001.

613

614

615

616

617

**Figure 4. Phylogenetic Tree of HTLV-1 Based on Concatenated gag-pol-env-tax Gene Sequences**

618

619

Phylogenetic analysis of *gag-pol-env-tax* genes used the NJ method with the GTR model (gamma=0.4815), confirmed by Maximum Likelihood method (data not shown). The phylogenetic tree included 55 HTLV-1 genomes of genotypes a, b and c, along with the seven

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621
new sequences generated in this study (highlighted in bold red). A previously published
sequence from an ATL case in French Guiana is shown in bold. Since the concatenated
sequences from PH1040 and PH1002 were identical, only one was retained to avoid
redundancy. Five Australo-Melanesian HTLV-1c sequences were used as outgroup. Tree
topology was consistent across individual gene analyses (data not shown). Horizontal branch
lengths are to scale, with the bar indicating 0.004 nucleotide replacement per site. Numbers on
nodes represent the probability (aLRT) of the monophyletic group.

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Abbreviations: a-TC, a-Transcontinental; a-JPN, a-Japan; a-NA, a-North African; a-SEN, a-Senegalese; a-G-rec, a-Guinean/Ghanaian recombinant; a-WA, a-West African; AUS, Australia; BRA, Brazil; CAN, Canada; CPV, Cape Verde; CHI, China; CIV, Cote d'Ivoire; DRC, Democratic Republic of Congo; FRA, France; FrGu, French Guiana; GER, Germany; GUI, Guinea; IRN, Iran; JPN, Japan; MAL, Mali; MAU, Mauritania; NCD, New Caledonia; ROU, Romania; SEN, Senegal; SOL, Solomon Islands; VAN, Vanuatu.

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<figure><img src="image_2.png" /><figcaption>**Figure 1.** Geographic distribution of hospital diagnosis for ATL treated in French Guiana over the past 30 years.</figcaption></figure>
<figure><img src="image_3.png" /><figcaption>Figure 2. Age and ethnic distribution of ATL cases and HTLV-1 prevalence in French Guiana.</figcaption></figure>

<figure><img src="image_4.png" /></figure>
<figure><img src="image_5.png" /><figcaption>Figure 3. Kaplan–Meier survival curves of ATL cases by clinical and demographic characteristics.</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>Figure 4. Phylogenetic Tree of HTLV-1 Based on Concatenated gag-pol-env-tax Gene Sequences</figcaption></figure>
Adult T-cell Leukemia/Lymphoma (ATL)
Cases In French Guiana from 1990 to 2019

<figure><img src="image_7.png" /></figure>

Temporal Distribution of ATL Subtypes

<figure><img src="image_8.png" /></figure>

Ethnic Disparities in ATL Burden and Onset

<figure><img src="image_9.png" /></figure>
1 SUPPLEMENTAL

2 Supplemental Figure 1. Flow chart of the ATL cases included in the study, from 1990 to

3 2019 in French Guiana.

4 Eight cases were excluded, including 1 duplicate, 1 ATL case without clinical data, 6

5 suspected ATL cases without confirmation.

<figure><img src="image_10.png" /></figure>

6

7 Supplemental Figure 2. Temporal Trends in ATL Numbers and Subtype Distribution in

8 French Guiana (1990–2019).

<figure><img src="image_11.png" /></figure>

9
<table><caption>10 Supplemental Table 1. Comparison of ATL Patient Characteristics Between Maroon and Creole Groups
11</caption><thead><tr><th></th><th>Overall</th><th>Maroon</th><th>Creole</th></tr></thead><tbody><tr><td><strong>Total</strong></td><td>137</td><td>94</td><td>40</td></tr><tr><td>N female (%)</td><td>72 (53%)</td><td>45 (48%)</td><td>26 (65%)</td></tr><tr><td>Median age (range)</td><td>58 (18-86)</td><td>43 (18-86)</td><td>58 (35-82)</td></tr><tr><td><strong>Country of birth</strong></td><td></td><td></td><td></td></tr><tr><td>Surinam</td><td>58 (42.3%)</td><td>57 (60.6%)</td><td>0 (0%)</td></tr><tr><td>French Guiana</td><td>44 (32.1%)</td><td>13 (13.8%)</td><td>31 (77.5%)</td></tr><tr><td>French Guiana or Surinam</td><td>24 (17.5%)</td><td>24 (25.5%)</td><td>0 (0%)</td></tr><tr><td>Caribbean islands*</td><td>6 (4.4%)</td><td>0 (0%)</td><td>6 (15%)</td></tr><tr><td>Guyana</td><td>3 (2.2%)</td><td>0 (0%)</td><td>2 (5%)</td></tr><tr><td>Brazil</td><td>1 (0.7%)</td><td>0 (0%)</td><td>1 (2.5%)</td></tr><tr><td>Ivory Coast</td><td>1 (0.7%)</td><td>0 (0%)</td><td>0 (0%)</td></tr><tr><td><strong>ATL subtypes</strong></td><td></td><td></td><td></td></tr><tr><td>Lymphoma</td><td>83 (61%)</td><td>57 (61%)</td><td>25 (63%)</td></tr><tr><td>Acute</td><td>46 (34%)</td><td>32 (34%)</td><td>12 (30%)</td></tr><tr><td>Smoldering</td><td>5 (4%)</td><td>2 (2%)</td><td>3 (8%)</td></tr><tr><td>Chronic</td><td>3 (2%)</td><td>3 (3%)</td><td>0 (0%)</td></tr></tbody></table>
<table><caption>13 Supplemental Table 2. Evolution of ATL cases description over three decades, from 1990 to 2019 in French Guiana.</caption><thead><tr><th>Decade of diagnosis</th><th>1990-1999</th><th>2000-2009</th><th>2010-2019</th><th>P-value</th></tr></thead><tbody><tr><td>Nb of ATL</td><td>39</td><td>40</td><td>58</td><td></td></tr><tr><td>ATL subtypes, n (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>Lymphoma</td><td>16 (41%)</td><td>27 (68%)</td><td>37 (64%)</td><td>NS</td></tr><tr><td>Acute</td><td>19 (49%)</td><td>12 (30%)</td><td>18 (31%)</td><td></td></tr><tr><td>Smoldering</td><td>2 (5%)</td><td>0 (0%)</td><td>3 (5%)</td><td></td></tr><tr><td>Chronic</td><td>2 (5%)</td><td>1 (3%)</td><td>0 (0%)</td><td></td></tr><tr><td>Female, n (%)</td><td>21 (54%)</td><td>17 (43%)</td><td>34 (59%)</td><td>NS</td></tr><tr><td>Maroon, n (%)</td><td>26 (67%)</td><td>31 (78%)</td><td>37 (64%)</td><td>NS</td></tr><tr><td>Median age</td><td>45</td><td>49</td><td>49.5</td><td>NS</td></tr><tr><td>Estimated population*</td><td>134,000</td><td>194,000</td><td>264,000</td><td></td></tr><tr><td>Annual incidence estimate (per 100,000 per year)</td><td>2.9</td><td>2.1</td><td>2.2</td><td></td></tr></tbody></table>

15

18

<footnote n="16">16 *These estimates are derived from annual population figures reported by sources such as Worldometer and StatisticsTimes.com.</footnote>
<table><caption>Supplemental Table 3. Characteristics of HTLV-1 patients with whole genome sequencing, including seven ATL patients from French Guiana.</caption><thead><tr><th>ID</th><th>Country of origin</th><th>Ethnic group</th><th>Sex</th><th>Age at diagnosis</th><th>Clinical status</th><th>HTLV-1 subtype</th><th>HTLV-1 genome size (bp)</th><th>Accession number</th></tr></thead><tbody><tr><td>PH489</td><td>French Guiana</td><td>Creole</td><td>F</td><td>47</td><td>ATL</td><td>a-TC</td><td>9,035</td><td></td></tr><tr><td>PH561</td><td>French Guiana</td><td>Maroon</td><td>F</td><td>21</td><td>ATL</td><td>a-WA</td><td>9,039</td><td></td></tr><tr><td>PH1002</td><td>Martinique</td><td>Creole</td><td>F</td><td>41</td><td>ATL</td><td>a-TC</td><td>9,037</td><td></td></tr><tr><td>PH1040</td><td>French Guiana</td><td>Creole</td><td>F</td><td>51</td><td>ATL</td><td>a-TC</td><td>9,037</td><td></td></tr><tr><td>PH1209</td><td>NA<sup>1</sup></td><td>Maroon</td><td>M</td><td>35</td><td>ATL</td><td>a-WA</td><td>9,037</td><td>MN781154<sup>2</sup></td></tr><tr><td>PH1210</td><td>French Guiana</td><td>Maroon</td><td>F</td><td>33</td><td>ATL</td><td>a-WA</td><td>8,778</td><td></td></tr><tr><td>PH1503</td><td>Suriname</td><td>Maroon</td><td>M</td><td>60</td><td>ATL</td><td>a-WA</td><td>9,039</td><td></td></tr><tr><td>PH1505</td><td>NA<sup>1</sup></td><td>Maroon</td><td>M</td><td>41</td><td>ATL</td><td>a-WA</td><td>9,039</td><td></td></tr></tbody></table>

22 NA not available. ¹Country of birth either French Guiana or Suriname. ²Previously published sequence.

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