Abstract
Background
Sexually transmitted infections (STI) are a prominent health issue in Africa, especially in key populations such as men who have sex with men (MSM). Here, we present the baseline results of a 2-year longitudinal cohort in Togo.
Methods
A total of 200 MSM in Lomé, Togo, were included in the ANRS I MIE 12400/DepIST-H cohort, half living with HIV. High-risk HPV (hrHPV) detection was performed on anal smears. Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) were tested from urine, pharyngeal and anal swabs.
Results
Overall, median age was 23 years, hrHPV prevalence was 75.9%, and was significantly higher in HIV-positive MSM (p = 0.008). The most common hrHPV types were HPV16 and HPV35 (18.7% each). Overall, 55.4% of participants had abnormal anal cytology, the most frequent lesions being low-grade squamous intraepithelial lesions, (22.3% of HIV-positive and 15.2% of HIV-negative MSM). The overall prevalence of GC and CT infections was 32.5% and 32.0%, respectively. Clinical anal lesions, mostly condyloma, were detected in 46.0% of participants (n = 86).
Conclusions
These findings emphasize the high prevalence of STIs among MSM and confirm the unusual distribution of HPV types in West Africa, with HPV35 being highly prevalent. A national strategy regarding STI screening and HPV vaccination in this key population is needed.
Trial registration
NCT04910438 submitted on 2020-01-22.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12879-025-11338-y.
Keywords: HPV, Anal lesions, MSM, Sub-Saharan Africa, Bacterial STI, HIV
Background
Men who have sex with men (MSM) still bear a disproportionate burden of Human Immunodeficiency Virus (HIV) disease, accounting for 21% of new cases worldwide in 2021 [1]. In sub-Saharan Africa, the overall HIV prevalence among MSM is about 5 times higher than among men in the general population [2]. Due to their sexual practices and number of sexual partners, MSM also have high rates of sexually transmitted infections (STI) [3], and MSM living with HIV (MLWHIV) have been found to have a higher prevalence of STIs than HIV-negative MSM [4]. One of the most reported STIs in this population is human papillomavirus (HPV) infection. In Togo, despite the fact that homosexuality is criminalized under national legislation, this population can be targeted by health programs supported by international donors, granting them access to pre-exposure prophylaxis (PrEP) or HIV-related care. A previous study, conducted in Togo in 2017, found that the prevalence of high-risk HPV (hrHPV) was globally high among MSM and higher among MLWHIV than HIV-negative MSM (85.2% and 30.7%, respectively) [5]. Persistent hrHPV can contribute to the development of anal cancer, and about 90% of anal cancers are associated with HPV16 infection [6]. Several studies have suggested that there is a geographical difference in hrHPV type distribution in sub-Saharan Africa [7]. A gap in research has caused the sub-Saharan African region to lag in identifying and implementing concrete actions for MSM, even though HPV vaccination, systematic anal cancer screening, and treatment of anal high-grade lesions for MLWHIV have been demonstrated to prevent anal cancers in other regions [8, 9].
Other STIs, such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are highly prevalent among MSM in Africa [5]. Unfortunately, in low- and middle-income countries (LMIC), these screenings have not been incorporated into the routine care offered to MSM [9]. CT and GC infections are strongly associated with HIV infection, and MSM with recurrent anal infections may be at significantly heightened risk of HIV infection [10]. A systematic review on extra-genital STI showed that the prevalence of CT and GC anal infections varied among MSM from 0.2 to 24.0% and 2.1–23.0%, respectively [11]. An estimated 70% of CT and GC infections would go undiagnosed if MSM were screened only in the urogenital region [12], since most pharyngeal and rectal infections are asymptomatic. Currently, Togo’s STI management strategy is syndromic, meaning that only people with STI symptoms are treated, without a biological diagnosis.
The previous study we conducted among a MSM population in Togo was a cross-sectional study, and no cytological analyses nor antimicrobial resistance studies were performed [5]. Here we present the baseline results of a 2-year longitudinal cohort regarding the prevalence of hrHPV, high-grade anal lesions, bacterial STI and antimicrobial resistance among MSM living in Lomé, Togo, according to their HIV serological status.
Methods
Study design and participants
This study is a baseline analysis of the ANRS I MIE 12400 DepIST-H cohort study. This two-year longitudinal cohort study aimed to estimate the prevalence and incidence of anal lesions (condyloma, dysplasia and anal cancers) according to HIV status. Participants were enrolled between July 2021 and December 2021 at the Espoir Vie Clinic Center (EVT), a community-based health center in Togo specialized in HIV care and support for key populations, for a two-year follow-up. Recruitment was facilitated by peer educators and health mediators affiliated with EVT, who invited eligible individuals. The inclusion criteria for this study were: (i) being self-identified as MSM; (ii) aged 18 years or older; (iii) sign the informed consent form. Assuming anal dysplasia prevalences of 55% for HIV + and 29% for HIV- [13], with a 95% confidence level and 10% attrition, the sample size was estimated at 200 (100 HIV + and 100 HIV-). All participants were tested for HIV at inclusion.
Data and biological sample collection
Data were collected using a questionnaire administered face-to-face by social workers (survey mask developed on KoboToolbox). The questionnaire included information on sociodemographic characteristics, sexual behavior, STI history, and STI-related symptoms in the previous six months. Clinical examination was conducted by a physician trained for diagnosis and management of anal lesions and anal samples were collected by this same trained physician.
HIV, HBV, HCV, and syphilis screening
Blood samples were collected for HIV, syphilis, Hepatitis C Virus (HCV) and Hepatitis B HBs antigen (HBsAg) screening using SD BIOLINE HIV/Syphilis Duo®(Abbott, Santa Clara, CA, USA), Bioline™HCV (Abbott) and Alere Determine™ HBsAg tests (Abbott). Each HIV-positive test was confirmed using another rapid HIV test, the First Response®HIV1-2.O Card Test (Premier Medical, Maharashtra, India), according to national guidelines. In case of discordant results, samples were tested with the INNO-LIA®HIVI/II Score (Fujirebio, Gothenburg, Sweden) line immunoassay.
Other STIs and antimicrobial resistance
CT and GC PCR tests were performed on site using pharyngeal, anal, and urine samples collected with the Xpert®CT/GC kit (Sunnyvale, CA, USA). Positive specimens were sent to the French National Reference Center for bacterial STI. Mycoplasma genitalium (MG) molecular detection was only carried out for patients with urogenital symptoms. Detection of MG and macrolide resistance was performed using ResistancePlus MG kit (SpeeDx, London, UK) [14].
For GC resistance detection and CT typing, DNA extraction was performed using the MagNA Pure 96 DNA instrument (Roche Diagnostics, Basel, Switzerland). A specific Genovar L real-time single-plex PCR assay targeting the pmpH gene was used for CT typing [15]. GC resistance to fluoroquinolones was tested using the ResistancePlus GC test (SpeeDx). Specific PCRs targeting genes involved in antibiotic resistance were carried out to identify resistance to cyclin, 3rd -generation cephalosporins, and azithromycin. Two nested PCRs for the GC multi-antigen sequence typing scheme (NG-MAST; porB and tbpB genes) were used for typing (see Supplementary Table 1).
Herpes simplex virus Type 1 (HSV-1) and Type 2 (HSV-2) PCR were performed on anal swabs using the RealStar®HSV PCR Kit (Altona, Hamburg, Germany).
HPV typing
Anal smears were collected with Anex-Brush® (Rovers Medical, Netherlands) on ThinPrep™ Pap Test PreservCyt™ (Hologic, Marlborough, MA, USA). The samples were stored at 4 °C and sent to France for analysis. Nucleic acids were extracted using the STARMag96 × 4 Universal Cartridge Kit (Seegene, Seoul, Korea) on the MICROLAB NIMBUS (Seegene). HPV typing was performed using the Anyplex IITMHPV28 kit (Seegene) which detects: 12 hrHPV (i.e., 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59); eight intermediate-risk HPV (i.e., 26, 53, 66, 68, 69, 70, 73, 82), and eight low-risk or non-classified HPV (i.e., 6, 11, 40, 42, 43, 44, 54, 61).
Cytological analyses
Thin-layer cytological smears were prepared using Thinprep® technology on the Ilsa diagnostic system. Cytological results were classified following the Bethesda System classification: normal; atypical squamous cells of undetermined significance (ASC-US); ASC cannot exclude a high-grade lesion (ASC-H); low-grade squamous intraepithelial lesion (LSIL); or high-grade SIL (HSIL).
Statistical analysis
Participant characteristics were described using median with interquartile range (IQR) and proportions for continuous and categorical variables, respectively. Medians were compared using the Wilcoxon Mann-Whitney test, and proportions were compared using the Pearson chi-square test. The prevalence of STIs was reported with a 95% confidence interval (95%CI). All statistical analyses were performed with R software version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).
Ethics
The study involved human participants, and the protocol was approved by all participants, who provided written informed consent. The Bioethics Committee of the Ministry of Health in Togo (CBRS) approved the study protocol (N°039/2019/CBRS), and the study was registered on the Clinical Trial Registry: clinicaltrial.gov|NLM with the Registration number: NCT04910438 (submitted on 2020-01-22).
Results
Patients’ characteristics
A total of 200 MSM were included in this study; 100 were MLWHIV and 100 were HIV-negative. Overall, their median age was 23 years (IQR: 21–28) and was higher in the MLWHIV group than in the HIV-negative group (27 and 21 years, respectively; p < 0.001). One in five (17.5%) of the MSM self-identified as a woman, and almost half of them (47.5%) reported being in a couple with a woman (Table 1). Among the 100 MSM living with HIV, 14 were unaware of their HIV status at the time of enrollment with 2 reporting no knowledge of their status at all while 12 self-reported a previous negative test. All participants who were previously aware of their HIV-positive status were already receiving ART. None of the HIV negative MSM had used PrEP in the last 6 months.
Table 1.
Sociodemographic characteristics of study participants and hepatitis B, hepatitis C, syphilis, herpes simplex virus 1/2, and bacterial sexually transmitted infections among study participants according to HIV serological status, togo, 2022
| HIV - | HIV + | Total | p | |
|---|---|---|---|---|
| N = 100 | N = 100 | N = 200 | ||
| Sociodemographic characteristics | ||||
| Age (years), median IQR |
21 (20–25) |
27 (23–30) |
23 (21–28) |
< 0.0011 |
| Age class, years, n (%) | < 0.0012 | |||
| 18–24 | 72 (72.0) | 35 (35.0) | 107 (53.5) | |
| 25–29 | 21 (21.0) | 33 (33.0) | 54 (27.0) | |
| ≥ 30 | 7 (7.0) | 32 (32.0) | 39 (19.5) | |
| Education level, n (%) | 0.1793 | |||
| Primary | 3 (3.0) | 5 (5.0) | 8 (4.0) | |
| Secondary | 45 (45.0) | 56 (56.0) | 101 (50.5) | |
| University | 52 (52.0) | 39 (39.0) | 91 (45.5) | |
| Marital status, n (%) | 0.3133 | |||
| Single | 88 (88.0) | 93 (93.0) | 181 (90.5) | |
| Divorced | 0 (0.0) | 1 (1.0) | 1 (0.5) | |
| Married | 1 (1.0) | 1 (1.0) | 2 (1.0) | |
| Living with a partner | 11 (11.0) | 5 (5.0) | 16 (8.0) | |
| Gender identity, n (%) | 0.074² | |||
| Cisgender | 97 (97.0) | 93 (93.0) | 190 (95.0) | |
| Transgender (M◊F) | 3 (3.0) | 7 (7.0) | 10 (5.0) | |
| Non-binary | 40 (40.0) | 51 (51.0) | 91 (45.5) | |
| Relationship status, n (%) | 0.144² | |||
| In a relationship with a woman | 43 (43.0) | 52 (52.0) | 95 (47.5) | |
| In a relationship with a man | 10 (10.0) | 6 (6.0) | 16 (8.0) | |
| Not officially in a relationship but in love with a man | 26 (26.0) | 31 (31.0) | 57 (28.5) | |
| None (living alone) | 21 (21.0) | 11 (11.0) | 32 (16.0) | |
| Sexually transmitted infections prevalence | ||||
| Hepatitis B, n (%) | 0.2463 | |||
| Negative | 100 (100.0) | 97 (97.0) | 197 (98.5) | |
| Positive | 0 (0.0) | 3 (3.0) | 3 (1.5) | |
| Hepatitis C, n (%) | ||||
| Negative | 100 (100.0) | 100 (100.0) | 200 (100.0) | |
| Syphilis, n (%) | ||||
| Negative | 100 (100.0) | 100 (100.0) | 200 (100.0) | |
| Neisseria gonorrhea, n (%) | 0.174² | |||
| Negative | 72 (72.0) | 63 (63.0) | 135 (67.5) | |
| Positive | 28 (28.0) | 37 (37.0) | 65 (32.5) | |
| Chlamydia trachomatis, n (%) | 0.544² | |||
| Negative | 66 (66.0) | 70 (70.0) | 136 (68.0) | |
| Positive | 34 (34.0) | 30 (30.0) | 64 (32.0) | |
| Herpes Simplex Virus 1/2, n (%)* | 0.170² | |||
| Negative | 97 (98.0) | 93 (93.0) | 190 (95.5) | |
| Positive | 2 (2.0) | 7 (7.0) | 9 (4.5) | |
1Wilcoxon-Mann-Whitney test
2Chi-square independence test
3Exact Fisher test
HBV, HCV, and syphilis prevalence
HBs Ag prevalence was 1.5% (95% CI: 0.5-4.0). All three participants who were HBsAg-positive were co-infected with HIV; and the prevalence of syphilis and HCV was 0.0% (Table 1).
Bacterial STI and anal HSV prevalence
The overall prevalence of GC and CT was 32.5% (95%CI = 26–39) and 32.0% (95%CI = 25.5–38.5), respectively (Table 1). The prevalence increased significantly with the number of sexual partners (p = 0.008 for GC and p = 0.016 for CT). The prevalence of GC was 3.0% in urine specimens, 22.0% in anal swabs, and 19.0% in pharyngeal swabs. The prevalence of GC in pharyngeal swabs was significantly higher in MLWHIV than in HIV-negative participants (25.0% and 13.0%, respectively, p = 0.031). The prevalence of CT was 8.0% in urine specimens, 26.0% in anal swabs, and 5.0% in pharyngeal swabs, with no differences by HIV serological status (Fig. 1). CT genotyping was performed on 73 specimens obtained from 64 patients. An L genovar was found in one anal specimen from an HIV-negative MSM participant. No significant association was found between anal lesions and anal GC or CT infection, except for an association between the presence of an anal fistula and anal CT infection (n = 3; p = 0.017; Table 2). Among the eight symptomatic patients tested for MG on urine specimen, one was found to be positive with no possible resistance assessment.
Fig. 1.
Prevalence of Neisseria gonorrhea (A) and Chlamydia trachomatis (B) infections detected at different sites among the study participants, according to their HIV serological status
Table 2.
Anal and urinary infections by Chlamydia trachomatis and Neisseria gonorrhoeae according to the presence of anal and or urinary symptoms
| No | Yes | Total | p | |
|---|---|---|---|---|
| Chlamydia trachomatis anal infection | n = 148 | n = 52 | n = 200 | |
| Anal discharge | 0.1661 | |||
| No | 147 (99.3) | 50 (96.2) | 197 (98.5) | |
| Yes | 1 (0.7) | 2 (3.8) | 3 (1.5) | |
| Anal ulceration | 0.9991 | |||
| No | 146 (98.6) | 51 (98.1) | 197 (98.5) | |
| Yes | 2 (1.4) | 1 (1.9) | 3 (1.5) | |
| Anal fistula | 0.017 1 | |||
| No | 148 (100.0) | 49 (94.2) | 197 (98.5) | |
| Yes | 0 (0.0) | 3 (5.8) | 3 (1.5) | |
| Anal fissure | 0.7611 | |||
| No | 138 (93.2) | 48 (92.3) | 186 (93.0) | |
| Yes | 10 (6.8) | 4 (7.7) | 14 (7.0) | |
| Chlamydia trachomatis urinary infection | n = 148 | n = 52 | n = 200 | |
| Genital discharge | 0.4531 | |||
| No | 147 (99.3) | 51 (98.1) | 198 (99.0) | |
| Yes | 1 (0.7) | 1 (1.9) | 2 (1.0) | |
| Genital ulceration | 0.9981 | |||
| No | 145 (98.0) | 51 (98.1) | 196 (98.0) | |
| Yes | 3 (2.0) | 1 (1.9) | 4 (2.0) | |
| Urinary symptoms | 0.9981 | |||
| No | 142 (95.9) | 50 (96.2) | 192 (96.0) | |
| Yes | 6 (4.1) | 2 (3.8) | 8 (4.0) | |
| Neisseria gonorrhoeae anal infection | n = 156 | n = 44 | n = 200 | |
| Anal discharge | 0.9981 | |||
| No | 153 (98.1) | 44 (100.0) | 197 (98.5) | |
| Yes | 3 (1.9) | 0 (0.0) | 3 (1.5) | |
| Anal ulceration | 0.9991 | |||
| No | 153 (98.1) | 44 (100.0) | 197 (98.5) | |
| Yes | 3 (1.9) | 0 (0.0) | 3 (1.5) | |
| Anal fistula | 0.5271 | |||
| No | 154 (98.7) | 43 (97.7) | 197 (98.5) | |
| Yes | 2 (1.3) | 1 (2.3) | 3 (1.5) | |
| Anal fissure | 0.7391 | |||
| No | 144 (92.3) | 42 (95.5) | 186 (93.0) | |
| Yes | 12 (7.7) | 2 (4.5) | 14 (7.0) | |
| Neisseria gonorrhoeae urinary infection | n = 156 | n = 44 | n = 200 | |
| Genital discharge | 0.9981 | |||
| No | 154 (98.7) | 44 (100.0) | 198 (99.0) | |
| Yes | 2 (1.3) | 0 (0.0) | 2 (1.0) | |
| Genital ulceration | 0.9981 | |||
| No | 153 (98.1) | 43 (97.7) | 196 (98.0) | |
| Yes | 3 (1.9) | 1 (2.3) | 4 (2.0) | |
| Urinary symptoms | 0.6881 | |||
| No | 149 (95.5) | 43 (97.7) | 192 (96.0) | |
| Yes | 7 (4.5) | 1 (2.3) | 8 (4.0) |
The overall prevalence of anal HSV-1/2 DNA was 4.5% (n = 9), including seven participants among MLWHIV (7.0%) and two among HIV-negative participants (2.0%, p = 0.170; Table 1). All but one of these infections were HSV-2.
Antimicrobial resistance of N. gonorrhea
Antimicrobial resistance testing was available for 69 GC-positive samples from 53 patients (Table 3). GC-positive samples were found resistant to fluoroquinolones, tetracycline at high level and azithromycin at high level to 100%, 72.5% and 0.0%, respectively. Decreased of susceptibility and/or resistance to third-generation cephalosporins was suspected for 8.7% with a mosaic penA254 gene detection. Other non-mosaic penA genes not associated with resistance were identified as penA2 (42.1%), penA12 (33.3%), penA14 (7.01%), penA5 (5.2%), penA19 (1.7%) and penA208 (1.7%), respectively. Fourteen patients were infected in at least two sites, 6 with the same strain and 4 with different strains at each site; the remaining could not be classified. Thirteen porB alleles were found among the 45 sequences assessed, and the most frequent allele was 1923 (n = 19). Nine tbpB alleles were found among the 46 available sequences, and the most frequent allele was 2954 (n = 14).
Table 3.
Molecular determinants of resistance obtained on GC-positive samples
| Antibiotics resistance | GC-positive samples, % (n) |
|---|---|
| Decreased susceptibility or resistance to ceftriaxone/cefixime | |
| penA mosaic* | 8.7% (5/57) |
| Resistance to Quinolones | |
| GyrA mutation S91F | 100% (69/69) |
| High-level resistance to Tetracycline | |
| tetM acquisition | 72.5% (50/69) |
| High-level resistance to Azithromycin | |
| 23 S mutation C2611T | 0.0% (0/69) |
| 23 S mutation A2058G/A2058G | 0.0% (0/69) |
*penA mosaic alleles were penA254.001
Anal HPV infection prevalence
HPV screening was performed for all 100 MLWHIV and 99 HIV-negative participants. All 199 anal swabs but one had interpretable HPV typing results. In total, 151 anal swabs were positive for at least one hrHPV, resulting in a prevalence of 75.9% (95%CI: 70.0-81.8). hrHPV prevalence was significantly higher in MLWHIV than in HIV-negative MSM (MLWHIV: n = 84 of 100, 84.0% [95%CI: 76.8–91.2]; HIV-negative MSM: n = 67 of 99, 67.7% [95%CI: 58.5–76.9]; p = 0.008; Fig. 2A). Overall, the median hrHPV per anal specimen was 2 (IQR: 1–3, range: 0–7), with no differences according to HIV serological status (Fig. 2B). The prevalence of multiple hrHPV infections (i.e. >2 hrHPV) was significantly higher among MSM living with HIV (n = 58 of 100, 58.0%, 95%CI: 48.3–67.7) than among MSM not living with HIV (n = 37 of 99, 37.4%, 95%CI: 27.8–47.0; p = 0.04; Fig. 2A). The most common hrHPV types were HPV16 and HPV35 (18.7% each), followed by HPV51 and HPV58 (17.7% each) and HPV59 (15.2%; Fig. 2C). Overall, HPV18 was found in 8.5% of anal swabs. HPV52 was the only HPV type found at a significantly higher prevalence in HIV-positive MSM than in HIV-negative MSM (24.0% and 10.1%, respectively; p = 0.014). For the other hrHPV types, no difference in prevalence was observed between MLWHIV and HIV-negative participants.
Fig. 2.
A Prevalence of anal high-risk HPV infections among study participants; (B) Number of high-risk HPV types (hrHPV) detected in anal samples of hrHPV-positive men having sex with men (MSM) according to HIV serological status; and (C) Anal HPV type distribution among MSM according to HIV serological status
Among the hrHPV-positive MSM (n = 151), 31% (n = 46) harbored at least one hrHPV included in the bivalent vaccine, and 67% (n = 101) harbored at least one hrHPV included in the nonavalent vaccine. Regarding low-risk HPV types, the overall prevalence of HPV6 and HPV11 was 29.6% and 12.1%, respectively, with no difference between MLWHIV and HIV-negative participants.
Description of anal cytology and association with hrHPV detection
Evaluating sample quality, 7.5% of anal swabs (n = 15) were deemed unsatisfactory for cytological analysis. Overall, 55.4% (n = 102) of the 184 patients with interpretable anal swabs had abnormal cytology (61.7% in MLWHIV and 48.9% in HIV-negative patients). The distribution of cytology results according to HIV serological status and the presence of hrHPV are described in Fig. 3. MSM living with HIV had more frequent anal samples with normal cytology while positive for at least one hrHPV than did HIV-negative MSM (75% and 50%, respectively; p = 0.025; Fig. 3). The most frequent lesions in both groups of participants were LSIL, present in 22.3% of HIV-positive MSM and 15.2% of HIV-negative MSM. Overall, HSIL was detected in 4.5% of anal swabs. Among the nine participants with HSIL, six had an anal HPV16.
Fig. 3.
A Distribution of cytological findings in anal samples according to HIV serological status; (B) Proportion of patients presenting high-risk oncogenic HPV according to cytological data ASC-H: atypical squamous cells suggestive of high-grade squamous intraepithelial lesion; ASC-US: atypical squamous cells of undetermined significance; HSIL: high-grade squamous intraepithelial lesion; LSIL: low-grade squamous intraepithelial lesion
Among participants with HPV16 (n = 38), 18% had a normal cytology. ASC-US, LSIL, HSIL, and ASC-H cytological results were found in 29%, 32%, 16% and 5% of these participants, respectively.
Clinical examination
Anal lesions were detected during clinical examination in 42.7% of the participants (n = 85). The most prevalent lesions were condyloma (n = 40, 20.1%), followed by anal skin tags, which were more frequent among the MLWHIV group than in the HIV-negative group (24.0% and 11.1%, respectively; p = 0.017). The presence of condyloma was strongly associated with the presence of HPV6 or HPV11 anal infections (44.4% and 6.3%, respectively; p < 0.001; Table 4). An anal fissure was observed in six participants (3.0%), three in each group. The prevalence of anal lesions by HIV serological status is summarized in Supplementary Table 2. No anal cancer was observed in any of the clinical examinations.
Table 4.
Anal lesions among study participants based on HIV serological status, togo, 2022
| HIV-, n = 100 n (%) |
HIV+, n = 100 n (%) |
Total, n = 200 n (%) |
p | |
|---|---|---|---|---|
| Condyloma$ | 0.1571 | |||
| No | 76 (76.0) | 84 (84.0) | 160 (80.0) | |
| Yes | 24 (24.0) | 16 (16.0) | 40 (20.0) | |
| External condyloma | 0.3151 | |||
| No | 83 (83.0) | 88 (88.0) | 171 (85.5) | |
| Yes | 17 (17.0) | 12 (12.0) | 29 (14.5) | |
| Internal condyloma | 0.0711 | |||
| No | 85 (85.0) | 93 (93.0) | 178 (89.0) | |
| Yes | 15 (15.0) | 7 (7.0) | 22 (11.0) | |
| Genital condyloma | > 0.9992 | |||
| No | 99 (99.0) | 100 (100.0) | 199 (99.5) | |
| Yes | 1 (1.0) | 0 (0.0) | 1 (0.5) | |
| Anal fistula | 0.4972 | |||
| No | 100 (100.0) | 98 (98.0) | 198 (99.0) | |
| Yes | 0 (0.0) | 2 (2.0) | 2 (1.0) | |
| Hemorrhoidal thrombosis | 0.6212 | |||
| No | 99 (99.0) | 97 (97.0) | 196 (98.0) | |
| Yes | 1 (1.0) | 3 (3.0) | 4 (2.0) | |
| Anal skin tags | 0.01611 | |||
| No | 89 (89.0) | 76 (76.0) | 165 (82.5) | |
| Yes | 11 (11.0) | 24 (24.0) | 35 (17.5) | |
| Rectal polyp | > 0.9992 | |||
| No | 100 (100.0) | 99 (99.0) | 199 (99.5) | |
| Yes | 0 (0.0) | 1 (1.0) | 1 (0.5) | |
| Anal fissure | > 0.9992 | |||
| No | 97 (97.0) | 97 (97.0) | 194 (97.0) | |
| Yes | 3 (3.0) | 3 (3.0) | 6 (3.0) | |
| Gluteal abscess | > 0.9992 | |||
| No | 99 (99.0) | 99 (99.0) | 198 (99.0) | |
| Yes | 1 (1.0) | 1 (1.0) | 2 (1.0) | |
| Anal ulceration | > 0.9992 | |||
| No | 100 (100.0) | 99 (99.0) | 199 (99.5) | |
| Yes | 0 (0.0) | 1 (1.0) | 1 (0.5) |
$Presence of at least one anal (internal or external) condyloma
1Chi-square independence test
2Fisher exact test
Discussion
This study is one of the first to describe anal lesions related to HPV infection and other bacterial STIs among young MSM in Togo, West Africa [16]. Our findings indicate a high rate of anal hrHPV and bacterial STI prevalence. In addition, anal LSIL and HSIL were detected in 19.6% and 4.5% of participants, respectively.
Due to their sexual practices, MSM are particularly exposed to anal lesions. Unfortunately, few MSM have access to proctological care and services, particularly in sub-Saharan African countries where homosexuality is criminalized [17]. We report here that condyloma lesions and skin tags were the most common anal lesions, which was expected as the DepIST-H cohort is constituted of young MSM. In a Nigerian cohort of MSM, the prevalence of anal condyloma lesions was 43%, and factors associated with condyloma occurrence included HIV infection, receptive anal intercourse, and having multiple male sexual partners [18]. The frequency of condyloma, particularly internal condyloma, may have been underestimated in our study due to a lack of experience as proctology is underdeveloped in Africa because it is considered a taboo specialty, and the number of proctologists with expertise in treating MSM is limited [19]. There is a crucial need to train general practitioners and to offer clear follow-up care recommendations for MSM patients.
Regarding anal cytology, one of the few studies in Africa, the TRUST/RV368 cohort in Nigeria, has reported that 57% of MSM had anal cytological lesions with only 6% of HSIL [16]. We report similar results, with approximately half (55.4%) of participants having abnormal cytology. Median age in our study is relatively young, 21 years in the HIV-negative group and 27 years in the MLWHIV group, which may partially explain the absence of cancer diagnosis. However, given the high frequency of abnormal cytology, recommendations should include regular smear tests. Currently, there is no screening policy in place, and these tests are difficult for MSM to access in the West African context.
Regarding HPV anal infections, our findings of 75.9% of prevalence are in line with results of studies conducted among MSM in Central African Republic [20], Mali [21] and Nigeria [16] with 57%, 56% and 68% of anal hrHPV prevalence, respectively. We confirm the results of the first study conducted among MSM in Togo in 2017, with the prevalence of hrHPV and multiple hrHPV infections significantly higher among MLWHIV than among HIV-negative MSM and HPV16 and HPV35 being the most prevalent types (13% and 15%, respectively in 2017) [22]. In the same way, most common HPV types in the Central African study were HPV35, HPV58, HPV59, and HPV31 while HPV16 and HPV18 were present in a minority of samples [20]. In the Malian and Nigerian studies, HPV16 was the most prevalent type [16, 21]. This variability of HPV types distribution in Central and West Africa should be taken into account when planning vaccination programs, especially knowing that none of the available vaccines target HPV35. The attributable fraction of HPV35 in anal cancer in sub-Saharan Africa is unknown, but a study recently found that HPV35 is implicated in some cervical cancers [23]. Nonetheless, introducing any HPV vaccine in the West African MSM population could have prevented HPV16 infection in one-fifth of the DepIST-H study participants. Togo has recently opted to provide the bivalent vaccine against HPV to young adolescent girls (aged 9–14 years), and data are needed to help expansion of this program to key populations in the future. As these populations are highly affected by condylomas, with 36% of the participants of this cohort infected by either HPV6 and/or HPV11, introducing a wider targeted HPV vaccine could also be discussed for the MSM population.
This study reports a high prevalence of CT and GC infections, but no circulation of Lymphogranuloma venereum CT strains or active syphilis were observed in this population. With regard to syphilis, the absence of infection detected in this key population may be unexpected, but these results are consistent previous studies conducted in Togo (0% in men who have sex with men (MSM) and 0.6% in female sex workers) and other studies conducted among MSM in West Africa [24, 25].
We also observed a concomitant active HSV anal infection in 4.5% of participants, all of whom had an hrHPV anal infection and all but one of whom had a CT or GC infection. Inconsistent condom use and multiple partners may explain the high prevalence of CT and GC infections [26]. A significantly higher rate of GC infection in the throat was found in MSM living with HIV, however the sample size was very small and this result need to be confirmed in a larger cohort. Multi-antimicrobial-resistant gonococcus, defined as resistance to third-generation cephalosporin (3rdGC) associated with several other families of antibiotics (e.g., cyclin, macrolides, quinolones), is a bacterium on the WHO watch list [27]. In Togo, we did not observe any high-level resistance to 3rdGC or macrolides, which is reassuring. Unsurprisingly, the strains we identified were all resistant to fluoroquinolones, and three-quarters of the strains were highly resistant to cyclins.
New STI prevention strategies should be considered, including post-exposure prophylaxis with doxycycline, which has recently proven effective in trials among MSM and transgender women in France and in the US which showed a decrease by two-thirds of the incidence of chlamydia and early syphilis when doxycycline was taken within 72 h after condomless sex [28, 29]. In a Kenyan study of cisgender women, the lack of efficacy of doxycycline in preventing GC infection was also likely due to a high prevalence of resistance to tetracycline [30]. These results argue in favor of its use in MSM with a recent bacterial STI [28], but efficacy against gonococcus may be impaired. Several vaccines targeting gonococcus are currently being studied, and their use will be a key priority for sexual and reproductive health [31] in low and middle income countries. A challenge in the coming years will be to re-evaluate the syndromic approach for STI management strategy or to integrate systematic treatment regardless of the presence of clinical symptoms.
Our study has some limitations. First, enrollment only took place in Lomé, the capital city, so the study population may not be representative of the entire MSM population in Togo. Secondly, as with most studies conducted in key populations in West Africa, the participants of this study are relatively young due to social, cultural or religious norms and recruitment methods based on community-based networks and associations. This may limit the extension of these results to an older cohort. Another limitation is that only cytological analyses of smears were performed and no biopsies were taken to confirm anal lesions by histology. Due to the limited experience of providers in diagnosing clinically objectifiable anal lesions, it is possible that the frequency of these lesions was underestimated. However, this bias was mitigated by ongoing training provided by a proctologist both before and during the cohort implementation.
Conclusions
These initial data from the ANRS I MIE 12400 DepIST-H cohort highlight the high STI burden among the key population of MSM in Togo and the unusual distribution of HPV types in West Africa, with HPV35 being highly prevalent while not covered by any current HPV vaccines. Our data should help the implementation of the Centers for Disease Control and Prevention recommendations for HPV vaccination of MSM and immunocompromised people, including those living with HIV, up to age 26. Our data should encourage new approaches for (1) bacterial STIs prevention, such as prophylaxis with doxycycline, (2) the re-evaluation of biomolecular diagnostic integration for systematic treatment regardless of clinical symptoms and (3) follow-up data on STI persistence and resistance to antimicrobials. A national strategy for STI screening and HPV vaccination in the MSM key population in West Africa is urgently needed and should be implemented accordingly.
Supplementary Information
Acknowledgements
We thank all the study participants and the staff of the Espoir Vie Togo NGO in Lomé, Togo. We thank Arabella Touati, Marie Gardette (CHU Bordeaux), and Mary Mainardis (St. Louis, Paris) for technical assistance. We thank Manel Merimeche for his bioinformatics analysis.
Abbreviations
- ASC-H
ASC cannot exclude a high-grade lesion
- ASC-US
atypical squamous cells of undetermined significance
- CT
Chlamydia trachomatis
- GC
Neisseria gonorrhoeae
- HBsAg
Hepatitis B HBs antigen
- HCV
Hepatitis C Virus
- HIV
Human Immunodeficiency Virus
- HPV
human papillomavirus
- hrHPV
high-risk HPV
- HSIL
high-grade squamous intraepithelial lesion
- HSV-1
Herpes simplex virus Type 1
- HSV-2
Herpes simplex virus Type 2
- IQR
interquartile range
- LSIL
low-grade squamous intraepithelial lesion
- MG
Mycoplasma genitalium
- MLWHIV
MSM living with HIV
- MSM
Men who have sex with men
- STI
sexually transmitted infections
- 95%CI
95% confidence interval
Authors’ contributions
A.J.S., V.M.F., D.D., D.K.E., and C.C. conceptualized the study. A.P.A.E. and E.M. did the clinical visits and collected the samples. L.A. and J.G. are proctologist and infectiologist referent physicians. L.A. trained physicians to perform clinical anal examinations on-site in Lomé. M.S., M.Z., and A.C.D. performed and analyzed the laboratory analyses. C.B. and B.B. performed bacterial STI analysis for typing and antimicrobial resistance. V.M.F., A.J.S., and F.A.G.K. performed the data analysis and visualization. A.J.S., V.M.F., D.D., D.K.E., and C.C. drafted the manuscript and have accessed and reviewed the underlying data. All authors read and approved the final draft.
Funding
The study was funded by the “Agence Nationale de Recherche sur le sida et les hépatites virales (ANRS) I Maladies Infectieuses Emergentes”.
Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study involved human participants, and the protocol was approved by all participants, who provided written informed consent. The Bioethics Committee of the Ministry of Health in Togo (CBRS) approved the study protocol (N°039/2019/CBRS), and the study was registered on the ClinicalTrial.gov platform with the number NCT04910438.
Consent for publication
Not applicable.
Competing interests
C.C., J.G., and D.D. have received honoraria and travel grants for conferences from MSD, Gilead Sciences, and ViiV Healthcare. VMF has received honoraria and/or travel grants for conferences from AstraZeneca, Moderna, Copan, and Gilead. The other authors declare that they have no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Valentine M. Ferré and Arnold J. Sadio contributed equally to this work as first authors.
Charlotte Charpentier and Didier K. Ekouevi contributed equally to this work as last authors.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.