Abstract
Introduction
Anal cancer, though rare in the general population, is increasing among men who have sex with men (MSM), particularly those living with HIV. In Algeria, no clinical data on anal HPV or precancerous lesions were available until now.
Objective
To determine the prevalence of anal HPV infection, identify circulating high-risk genotypes, and estimate the frequency of anal dysplasia among MSM with HIV in Setif, Algeria.
Methodology
A cross-sectional study was conducted in 2024 among 57 MSM followed at the STI/HIV Reference Center in Setif. Anal HPV was detected by PCR (GeneXpert®), followed by high-resolution anoscopy with targeted biopsies. Histology was classified according to LAST (LSIL, HSIL).
Results
HPV infection was detected in 72% (41/57). HPV-16 and HPV-18 were the predominant genotypes, found in 42.1% and 35.1% of participants. Among the 41 biopsied patients, 85.4% had precancerous lesions, including 39% HSIL. Multiple HPV co-infections occurred in 24.3%. The main risk factors were condomless receptive anal intercourse, smoking, and chemsex.
Conclusion
This first Algerian study reveals a high prevalence of anal HPV infection and precancerous lesions among MSM with HIV. Findings support the urgent need for targeted screening, HPV vaccination, and strengthened prevention.
Introduction
Although rare in the general population, anal cancer has become increasingly common among men who have sex with men (MSM) living with HIV. 1 Persistent infection with human papillomavirus (HPV), particularly high-risk oncogenic genotypes, is now recognized as the main etiological factor in anal dysplasia and invasive anal cancer.2–4
More than 90% of anal cancers are attributable to high-risk HPV (HR-HPV) infections, particularly genotypes 16, 18, 52, and 58.3,5–7
This risk is markedly increased among MSM living with HIV, due to chronic immunosuppression, often elevated viral load, and risky sexual practices.4,8
International studies have shown that the incidence of anal cancer in this population is comparable to, or even exceeds, that of cervical cancer before the introduction of systematic screening by cervical smear.9–12
Early detection of anal dysplasia traditionally relies on anal cytology, complemented by high-resolution anoscopy (HRA). However, in Algeria, anal cytology is neither available nor routinely performed, and HRA remains the only screening method available in a few specialized centers.
To date, no clinical or epidemiological studies have been conducted in Algeria to assess the prevalence of HPV infection or anal precancerous lesions among MSM living with HIV. A recent cross-sectional study from Beirut, conducted in a comparable regional context, reported a high prevalence of anal HPV infection and dysplasia in this population. 2 However, data on circulating HPV genotypes, the frequency of anal lesions, and region-specific risk factors remain completely unavailable in Algeria.
Despite international recommendations aimed at reducing the burden of anal cancer in high-risk populations, the implementation of targeted screening programs and HPV vaccination remains limited in Algeria.12–14
This gap leads to an underestimation of the problem and delays the implementation of effective preventive measures.
The present study is the first of its kind in Algeria and aims to enrich regional knowledge on an emerging public health issue.
Méthodologie
Type and setting of the study
The present study is a cross-sectional, descriptive, and analytical study conducted between January and December 2024 at the STI/HIV/AIDS Reference Center in Setif, Algeria. This center provides medical, biological, and psychosocial follow-up for people living with HIV in eastern Algeria.
All participants were recruited consecutively among patients followed at this reference center, during routine visits for HIV monitoring or STI consultation.
Study population
The inclusion criteria were as follows:
Being male; Having sex with men (MSM); Living with HIV (HIV-1 or HIV-2);
Being 18 years of age or older; Having given informed consent for anal HPV screening and anoscopy.
Individuals with known anal lesions (fistulas, thrombotic hemorrhoids, diagnosed cancers) were excluded.
A total of 57 participants who met the criteria were included in the study.
Among these, 41 underwent high-resolution anoscopy HRA was performed for all participants presenting abnormal anal cytology and/or a positive HR-HPV test. Participants with normal cytology and negative HPV results were followed clinically without HRA.
Data collected
Data were collected using a structured questionnaire administered during consultation, supplemented by a review of medical records.
The variables studied included: • Sociodemographic data: age; level of education; occupation; marital status. • Sexual behavior: age of first sexual intercourse; total number of sexual partners during lifetime; practice of receptive anal intercourse; frequency of condom use; existence of paid sexual intercourse. • Toxic habits: tobacco, cocaine, and stimulant pill use. • Clinical and biological data: history of sexually transmitted infections (STIs), proctological symptoms, viral co-infections (HBV, HCV), immunovirological status (mean CD4 count, viral load), and antiretroviral treatment. All participants were screened for common STIs (syphilis, gonorrhea, chlamydia, herpes simplex virus) as part of their regular follow-up; results were recorded from medical files when available. At the time of inclusion, 100% of participants were receiving antiretroviral therapy (ART), and the proportion with undetectable viral load was documented.
Anal HPV screening
An anal swab was taken from each participant using a Dacron swab inserted 5 cm into the anal canal, rotated for approximately 30 s, then placed in a specific transport medium.
Human papillomavirus (HPV) genotypes were detected by real-time PCR (GeneXpert® HPV, Cepheid), specifically identifying: HPV-16, HPV-18/45, as well as a combined group of 11 other high-risk oncogenic genotypes (HR-HPV), including types 31, 33, 35, 52, 58, 51, and 59.
Internal quality controls were used according to manufacturer recommendations. Positive results for HPV DNA were classified according to genotype and further analyzed for associations with clinical and histological data.
High-resolution anoscopy and histology
High-resolution anoscopy was performed in 41 of the 57 participants. The examination was performed after applying 5% acetic acid and Lugol’s solution to the anal mucosa in order to visualize areas suspected of dysplasia. In the presence of epithelial abnormalities, targeted biopsies were performed.
The tissue samples were analyzed histologically and classified according to the LAST (Lower Anogenital Squamous Terminology) terminology, which distinguishes between: • Low-grade intraepithelial lesions (LSIL), • High-grade intraepithelial lesions (HSIL), • and invasive carcinomas, in cases of proven tumor progression.
All histological analyses were performed by experienced pathologists trained in HPV-related lesions.
Statistical analysis
Statistical analysis was performed using SPSS version 26 (IBM, USA).
Quantitative variables were described as mean ± standard deviation, while qualitative variables were expressed as absolute numbers and percentages.
Comparisons of qualitative variables were performed using Pearson’s Chi2 test, or Fisher’s exact test in the case of small sample sizes.
The threshold for statistical significance was set at p < 0.05.
Associations between HR-HPV infection, dysplasia, and potential risk factors (age, sexual behavior, smoking, CD4 count, viral load, ART status) were analyzed using bivariate tests. No multivariate model was built due to sample size limitations, which is acknowledged in the study limitations.
Results
The study included 57 men who have sex with men (MSM), with a mean age of 33.7 ± 6.9 years (range: 19–53). In terms of educational attainment, 28% of participants (n = 16) had no formal education, 26% (n = 15) had completed primary education, 19% (n = 11) had completed secondary education, and 26% (n = 15) had completed higher education. Regarding marital status, the majority were single (63%, n = 36), compared to 37% (n = 21) who were married.
Sociodemographic, behavioral, and clinical characteristics of MSM living with HIV (n = 57).
Behavioral characteristics
Psychoactive substance use was notable: 82.5% (n = 47) reported smoking tobacco, 57.9% (n = 33) used psychoactive substances in a sexual context (chemsex), and 21.1% (n = 12) had used cocaine. The average age at first sexual intercourse was 14 years, with some participants reporting that they had first had sex as early as 10 to 12 years of age. Nearly 30 participants had their first sexual intercourse between the ages of 10 and 14, and 27 between the ages of 15 and 19. The average number of sexual partners during their lifetime was high, with a mean of 13 partners (range: 1–28).
Receptive anal intercourse was reported by 84% of participants (n = 48). Condom use remained uneven: one-third reported never using them (n = 20), another third only occasionally (n = 18), and the last third systematically (n = 19). The majority of participants (81%, n = 46) reported not engaging in paid sex.
Clinically, participants frequently reported proctological symptoms: 40% suffered from anal pruritus (n = 23), 33% from anal lesions or masses (n = 19), 32% from bleeding (n = 18), and 35% from discomfort during defecation (n = 20). Less frequently, pain (19%, n = 11) or anal discharge (23%, n = 13) were reported.
Factors associated with anal dysplasia among MSM living with HIV (n = 57).
Significant threshold: p < 0.05. There was a strong association between anal HPV infection and histologic dysplasia (p < 0.001).
No dysplasia was observed among HPV-negative participants.
Other variables (age, smoking, CD4 count, condom use, or viral suppression) were not significantly associated with dysplasia.
Clinical and immunovirological data
With regard to sexually transmitted infections (STIs), 74% of participants (n = 42) were carriers of at least one STI. The most common were chlamydia (18%, n = 10), condylomas (16%, n = 9), syphilis (16%, n = 9), gonorrhea (14%, n = 8), and herpes (11%, n = 6).
In addition, cases of co-infections were noted: 4 participants were carriers of hepatitis B virus (HBV), 2 of hepatitis C virus (HCV), and 10 had multiple HR-HPV co-infections.
HIV infection was relatively well controlled overall: 82.5% of participants (n = 47) had an undetectable viral load, with a mean current CD4 count of 518.9 ± 257.4 cells/mm3 (range 104–890). The reported mode of transmission was predominantly heterosexual (35%, n = 20), followed by bisexual intercourse (21%, n = 12), exclusively homosexual intercourse (19%, n = 11), All participants were receiving antiretroviral therapy.
Anal HPV infection and histologic findings
Human papillomavirus (HPV) infection was highly prevalent. The HPV test was positive in 72% of participants (n = 41). HPV-16 was found in 42.1% and HPV-18 in 35.1%, while 28% (n = 16) had a negative HPV test. Several cases of multiple HR-HPV infections were identified, including complex combinations such as HPV 16 + 18 + 45; HPV 16 + 31 + 33 + 35 + 52 + 58; and HPV 18 + 45 + 51 + 59.
Association between histologic lesion grade and HR-HPV genotypes (n = 41 biopsied cases).
*Significance threshold: p < 0.05.
The overall association between HR-HPV genotypes and histologic grade was highly significant (p < 0.001).
HSIL lesions were associated with HPV-16 in 8 cases, HPV-18 in 10 cases, and with other HR genotypes in 6 cases, including 6 multiple infections.
ASC-US cases included HPV-16 infections in 9 participants, HPV-18 in 2 participants, and one HPV-16 + HPV-18 + HPV-45 co-infection.
LSIL was associated with HPV-16 (n = 5), HPV-18 (n = 4), and one other high-risk genotype (n = 1), including one multiple infection.
Among participants with normal histology, three carried HPV-18, one carried a multiple HPV-16 + 31 + 33 + 35 + 52 + 58 infection, and one carried a HPV-18 + 45 + 51 + 59 co-infection. All corresponding genotype distributions by histological category are documented in Table 3.
The overall association between HR-HPV infection and the presence or severity of anal dysplasia was statistically significant (p < 0.001, Fisher’s exact test) (Table 2 and Table 3).
No significant association was found with age, CD4 count, smoking, or chemsex practices.
Discussion
Our study highlights a high prevalence of anal HPV infection (72%) and precancerous lesions (85.4 %)among those undergoing HRA)—including histological abnormalities such as ASC-US, LSIL, and HSIL—among men who have sex with men (MSM) living with HIV in Setif. These results, supported by statistically significant associations between HR-HPV infection and the presence or severity of dysplasia (p < 0.001), confirm the increased vulnerability of this population to human papillomavirus (HPV) infection and anal dysplasia (Table 3).
The data obtained are consistent with several international studies. For example, Abi Aad et al. (2024) reported a similar prevalence among MSM living with HIV in Lebanon. 2 Similarly, Palefsky et al. (1998) reported a 65% rate of anal HPV infection among HIV-positive MSM in the United States. 15 A meta-analysis of more than 29,000 participants conducted by Wei et al. (2021) also confirmed a high prevalence of infection and a significant proportion of high-grade lesions in this at-risk population. 16
At the same time, a systematic review conducted by Machalek et al. (2012) revealed that 70 to 90% of MSM living with HIV have anal HPV infection, 9 while Wasserman et al. (2017) emphasized the importance of targeted screening due to the high risk of progression to precancerous lesions or even invasive anal cancer. 17
Our findings (72% overall HPV prevalence) are fully in line with these international data, reinforcing the global evidence that HIV-related immunosuppression and risky sexual practices maintain a very high burden of anal HPV infection even in resource-limited settings.
In France, Donà et al. (2012) 18 reported a prevalence of 72.5% of anal HPV infection among MSM at risk, 56.1% of whom were carriers of high-risk genotypes. In Spain, Alemany et al. (2015) detected HPV DNA in 78% of anal carcinomas, with a predominance of genotype 16. 3 These converging results demonstrate that HPV-16 remains the most oncogenic and widely distributed genotype in MSM cohorts worldwide, including our Algerian population.
In Asia, Yang et al. (2012) observed a prevalence of 66% among HIV-positive MSM in Beijing. 19 Similarly, Guimarães et al. (2011) reported an overall prevalence of 65.6% among MSM living with HIV in Brazil, 20 reaching up to 86% in some subgroups. This variability underscores the influence of regional, behavioral, and virological factors in HPV transmission dynamics.
High-risk HPV genotypes
HPV-16 was detected in 42.1% (24/57) of participants, and HPV-18 in 35.1% (20/57), making them the predominant oncogenic genotypes in the cohort. These results are consistent with several studies on MSM living with HIV. For example, a South African study conducted by Müller et al. (2016) revealed a high prevalence of HPV-16 (32%) and HPV-18 (21%) in this population. 10 Similarly, Combes et al. (2018) in France showed a similar distribution of oncogenic types among HIV-positive MSM. 11
Our findings confirm that HPV-16 and HPV-18 are the most strongly associated with HSIL (p < 0.001), which aligns with their established carcinogenic potential in anal mucosa.
Recent data from a multicenter cohort also report a high prevalence of high-risk genotypes, particularly HPV-16 and HPV-58. 21
Multiple HR-HPV infections were observed in 24.4% of our participants, a finding consistent with the HIM Study (Nyitray et al., 2011). 22 Such co-infections may enhance viral persistence and increase the likelihood of malignant transformation.
Anal dysplasia and precancerous lesions
The frequency of high-grade lesions (HSIL) observed in our study (39%) is broadly consistent with estimates reported in the literature. Palefsky et al. (1998) identified a 25% prevalence of HSIL in HIV-positive MSM in the United States. 15 Furthermore, the meta-analysis by Machalek et al. (2016) estimated that 29–47% of MSM living with HIV have HSIL. 23
In our cohort, the significant correlation between HR-HPV infection and HSIL (p < 0.001) confirms the causal relationship observed in larger cohorts, despite the smaller sample size.
In South Africa, Müller et al. (2016) found a 57.6% prevalence of anal infection with high-risk HPV genotypes among MSM living with HIV, 10 suggesting a similar risk context. Our data thus confirm that North African MSM living with HIV face a comparable oncogenic burden.
Risk factors
Our study identifies several behavioral factors associated with the occurrence of precancerous anal lesions in MSM living with HIV. Unprotected receptive anal intercourse, reported by 84.2% of participants, remains the main route of exposure. Smoking, reported by 82.5%, is another major factor.
Indeed, Wieland et al. (2015) showed that smoking is significantly associated with higher anal HR-HPV viral load, 24 and this was supported by Umutoni et al. (2022). 25
Although in our analysis smoking was not statistically significant (p = 0.72), the very high prevalence suggests a cumulative contribution to mucosal vulnerability.
Furthermore, chemsex practices were reported by more than half of our participants (57.9%), reflecting behavioral patterns that increase exposure to STIs and HPV.
Cranston et al. (2012) 26 and Hernandez et al. (2013) 27 both showed that drug use and recurrent STIs (especially Chlamydia and Herpes simplex virus) favor persistence of HR-HPV through chronic inflammation.
In our sample, dysplasia tended to be more frequent among chemsex users (p = 0.076), a trend consistent with these findings.
These results confirm the need for a multidimensional prevention strategy integrating behavioral interventions, STI management, and HPV screening among MSM living with HIV.
HIV-specific data
The mean CD4 count observed (518 cells/mm3) and the high rate of undetectable viral load (82.5%) reflect effective ART adherence. However, despite immune restoration, HPV persistence and HSIL occurrence were not significantly correlated with CD4 level (p = 0.83).
A meta-analysis by Kelly et al. (2020) 28 showed that ART does not significantly reduce HR-HPV prevalence or HSIL incidence. Similarly, Palefsky et al. (2001) 29 demonstrated that even under HAART, HPV-associated lesions may persist or progress.
This highlights the limited protective effect of ART on HPV-driven carcinogenesis, supporting the need for continuous screening irrespective of immune status.
Regional comparison and screening implications
In North Africa, epidemiological data on anal HPV infection among MSM living with HIV remain scarce. No national studies have yet been published in Algeria or neighboring countries.
Our results therefore provide the first regional evidence confirming that MSM living with HIV in Algeria are similarly exposed to HR-HPV and its oncogenic sequelae.
In this context, the implementation of targeted screening programs, even in the absence of cytology infrastructure, becomes a priority.
If high-resolution anoscopy (HRA) is not available, alternative molecular biomarkers such as HPV DNA methylation assays or E6/E7 mRNA testing may represent feasible options, as suggested by recent studies.
The ANCHOR study (Palefsky et al., 2022) 30 demonstrated that treatment of HSIL significantly reduces progression to invasive anal cancer. Likewise, Natale et al. (2024) 31 emphasized that combining cytology, HPV genotyping, and HRA is the optimal prevention strategy. 32
These results support the urgent need to integrate anal screening into HIV care services in Algeria.
Limitations
This study has several limitations that should be acknowledged.
The sample size was relatively small (n = 57) and recruited from a single reference center in Setif, which may limit the generalizability of our findings to all MSM living with HIV in Algeria. However, this cohort remains representative of a key at-risk group in eastern Algeria and provides valuable first-hand data in a setting where no previous studies exist.
The cross-sectional design precludes any causal inference regarding the relationships between behavioral factors, immune status, and the occurrence of anal dysplasia. Longitudinal follow-up studies would be needed to assess the persistence and progression of HPV-related lesions.
Cytological screening was not available, as anal cytology is not routinely performed in Algeria. This limited our ability to compare cytological and histological results, or to assess the diagnostic performance of cytology versus HRA in this population.
Although participants were tested for major STIs (syphilis, gonorrhea, chlamydia, HSV, HBV, HCV), not all results were systematically available, and co-infections might have been underestimated. Likewise, data on viral load fluctuations and ART adherence over time were not longitudinally analyzed.
The study did not include HPV genotyping beyond the major high-risk types (HPV 16, 18, and grouped HR-HPV). The absence of full genotype sequencing may have underestimated the diversity of HPV strains circulating in this population.
Despite these limitations, this study provides the first clinical and molecular data on anal HPV infection and dysplasia among MSM living with HIV in Algeria, and thus represents a significant step toward the establishment of targeted prevention and screening programs in North Africa.
Conclusion
This study represents the first documented clinical investigation in Algeria of anal HPV infection and dysplasia among MSM living with HIV. Our results highlight a high prevalence of HR-HPV (72%) and a substantial proportion of HSIL (39%), comparable to findings from higher-resource settings.
Despite effective ART and good immune restoration, the persistence of HR-HPV and occurrence of HSIL confirm the need for continuous, structured screening in this population.
A national prevention strategy should include anal cytology, HRA, and HPV genotyping, alongside HPV vaccination programs for MSM and people living with HIV.
As emphasized by Uusküla et al. (2025), 3 an integrated prevention strategy combining screening and vaccination is essential to effectively combat HPV-related cancers in vulnerable populations.
Footnotes
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
