HIV–HPV Syndemic and Anal Precancerous Lesions Among MSM and Transgender Women in Pakistan: A Biological Continuum in High-Risk Sexual Networks
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Background
Sexual and gender minorities (SGM), including men who have sex with men (MSM) and transgender women, often face stigma, legal constraints, and limited access to sexual and reproductive health services. These conditions restrict prevention and care, increasing vulnerability to HIV and human papillomavirus (HPV) infections. While strong HIV–HPV interaction is documented in high-income settings, evidence from low- and middle-income countries remains limited. This study examines the burden, co-infection dynamics, and progression of HPV infection and anal dysplasia among MSM and transgender women in Pakistan.
Methods
A cross-sectional study was conducted between 15/09/2015 and 25/10/2016 among MSM and transgender women recruited from sexual health and antiretroviral therapy centers in Karachi. Eligible participants were aged ≥18 years and self-reported anal sex within the past 6 months (N=298). Two anal specimens were collected for HPV DNA detection and genotyping using PCR, and anal squamous intraepithelial lesions (ASIL) were assessed cytologically using the Bethesda classification. Associations were estimated using Cox proportional hazards regression algorithms to derive prevalence ratios (PRs).
Results
Among participants, 44% (n=133) were living with HIV. Overall HPV prevalence was 65.1%, rising to 87% among HIV-positive individuals compared to 48% among those without HIV (χ²p≤0.001). Likewise 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV (χ²p≤0.001). HIV infection was strongly associated with HPV acquisition (adjusted PR 2.81, 95% CI 2.16–3.82). Among HPV-positive participants (n=194), 58.8% were co-infected with HIV. High-risk HPV was highly prevalent among those living with HIV (83.2% vs. 35.3% (χ²p≤0.001)), with HPV16 as the dominant oncogenic type. Multiple HPV infections were more common among HIV-positive individuals (χ²p≤0.001), and HIV seropositivity was 3.43 (95% CI: 2.55–3.51) times higher among those with high-risk HPV. Co-infected participants demonstrated prolonged smoking, longer duration of sex work, high-intensity sex work with limited condom negotiation, and higher prevalence of anal warts (all p<0.05). Anal dysplasia (ASIL) was present in 35% of participants and was higher among HIV-positive individuals (42.4% vs. 28.1%, p<0.001). HIV–HPV co-infection was independently associated with ASIL (adjusted PR 1.75, 95% CI 1.07–2.88), while high-risk HPV further amplified this risk (PR 3.04, 95% CI 1.75–5.26).
Conclusion
These findings demonstrate a biological continuum in HIV-positive MSM and transgender women, where HIV increases HPV acquisition, persistence, and multiplicity, accelerating progression to anal dysplasia. This reflects a syndemic shaped by biological interaction and structural vulnerability. Integrating HPV screening and vaccination within HIV services is essential to interrupt progression to cancer in this high-risk population.
What this study adds
This study provides context-specific evidence from Pakistan, a country experiencing a rapidly expanding HIV epidemic with low diagnosis and treatment coverage. It demonstrates a higher burden of high-risk and multiple HPV infections among individuals living with HIV and shows that HIV seropositivity was more than threefold higher among participants with high-risk HPV infection. These findings highlight a biological continuum linking HIV infection, HPV multiplicity, and anal dysplasia, and underscore the urgent need for integrated HIV–HPV prevention strategies in high-risk populations.
