The findings from this descriptive cross-sectional study of HIV-infected women enrolled in the COMPASS-DUST study [14] provide significant insights into the prevalence and risk factors associated with high-risk human papillomavirus (HR-HPV) infections in this vulnerable population. Our study reveals that one in seven of the participants have HR-HPV infections at baseline while the prevalence of multiple HR-HPV infections was considerably lower, with only one in 27 women affected. None of the baseline participants’ factors was associated with HR-HPV infections. However, having a serum CD4+ cell count below 560 cells/µL and a co-infection with either HPV 16 or 18 genotype were significantly associated with the detection of multiple HR-HPV infections.
The prevalence of HR-HPV infections (13.4%) recorded in our study aligns with existing literature across the world, suggesting that HIV-infected individuals have a high burden of HPV infections [8]. This figure is, however, lower than the prevalence of 24.5% reported by Ezechi et al. in 2014 [12] among a predominantly similar population of women in another clinical setting in Lagos, Nigeria, and even much lower than the 42.6% recorded in a recently published study by Traore et al. [18] in Bamako, Mali, and the reported pooled estimates of 64.0% by Menon et al. in 2016 [19] and 51.0% by Bogale et al. in 2020 [20] in two systematic reviews and meta-analyses among HIV infected women in Kenya and developing countries respectively. The higher prevalence rates in these studies may be influenced by regional variations in HPV epidemiology, variations in the diagnostic methods or sensitivity of HR-HPV detection techniques, temporal differences in the study periods reflecting changes in public health interventions or HIV care, and potential variations in implementation, adherence and efficacy of antiretroviral therapy (ART) across different settings. Notably, our study enrolled only sexually active women on ART with well-controlled HIV who are otherwise healthy, hence, the relatively lower HPV prevalence we recorded.
Our study revealed that 3.7% of the enrolled WLHIV had multiple HR-HPV genotype infections. This prevalence is notably close to the 8.2% reported in a 2014 study among HIV-positive women in a similar geographical setting in Lagos, Nigeria [12]. This is, however, at substantial variance from the broader Sub-Saharan Africa regional estimates of 22.6% prevalence reported in a 20-year systematic review of WLHIV [21]. These variations in study findings may be due to regional variations in HPV epidemiology, temporal differences in the study periods reflecting changes in public health interventions or HIV care, and the population characteristics as reflected in our study where only ART adherent and healthy HIV-infected women with well-controlled infections were enrolled.
Similar to the finding by Bogale et al. [20] in 2020, HPV 16 was the most prevalent HPV genotype (20.0%) in our study as reported in most of the existing literature [1,12]. This finding was, however, different from a previous review which reported HPV 52 as the most prevalent genotype (26.0%) among HIV-infected women [19]. HPV 52 (17.2%) is the second predominant HPV genotype observed in this current study. Our findings also underscore the predominant presence of HR-HPV types 16, 31, 51, 52, and 58, among which only HPV type 16 is covered by the currently approved and available vaccines (Cervarix and Gardasil) [22,23] adopted for the Vaccine Alliance (Gavi)-supported vaccine roll-out programs in Nigeria which started in October 2023 [24]. This further highlights the observations of several other studies reporting a high frequency of non-vaccine HPV types among WLHIV in Sub-Saharan Africa [21], thus, the need to reinforce the implementation of population-based HR-HPV screening programs as a crucial step in preventing cervical cancer among WLHIV across the Sub-Saharan Africa region. The age-specific prevalence rates of HR-HPV infections among WLHIV, as depicted in our study reveal a distinct trend of decreasing prevalence with increasing age [25–27]. The high prevalence seen in women aged 25–39 years is consistent with the epidemiological understanding of HR-HPV infections, where younger women tend to have higher prevalence rates due to factors such as higher rates of sexual activity, new sexual partnerships, and potentially less robust immune responses compared to older women [28] while the second peak in the 50–54 years age group may be attributable to factors such as hormonal changes associated with menopause which affect vaginal and cervical epithelium, making it more susceptible to HPV infections [27]. Additionally, immune senescence, or the natural decline in immune function with age [29], may contribute to the reactivation or persistence of latent HR-HPV infections in older women.
Our study found no significant association between the baseline participant factors and HR-HPV infections, and this lack of association suggests that HR-HPV infections may be widespread across various demographic and behavioural profiles within the population of WLHIV. It also highlights the potential influence of the immunosuppressive state induced by HIV on the susceptibility to HR-HPV, overshadowing other sociodemographic and behavioural risk factors. However, our study identified that specific factors such as CD4+ cell count below 560 cells/µL and HPV 16 or 18 co-infection were associated with multiple HR-HPV infections. The finding of a significantly higher risk of HPV infections among HIV-infected women with a serum CD4+ cell count below 560 cells/µL is consistent with the findings from previous studies where a higher HR-HPV prevalence was recorded in HIV-infected women with lower CD4+ cell counts [12,30]. This is based on the understanding that a lower CD4+ cell count, indicative of more advanced immunosuppression, impairs the body's ability to clear HPV infections, thereby increasing the likelihood of multiple HR-HPV infections [30]. This finding emphasizes the importance of maintaining optimal immune function through ART to mitigate the risk of HPV co-infections and their potential complications in WLHIV. Furthermore, the finding of an independent association between HPV 16 or 18 co-infection and multiple HR-HPV infections suggests a synergistic pathogenic mechanism that exacerbates the infection risk and the high oncogenic potential of HPV 16 and 18 responsible for a significant proportion of cervical cancers globally [1,31] which underscores the need for extended-spectrum genotype-specific monitoring and interventions.
The findings of our study have several important implications. Firstly, they highlight the critical need for regular and comprehensive HPV screening programs in addition to vaccinations among WLHIV. Secondly, the association between lower CD4+ cell counts, and multiple HR-HPV infections reinforces the importance of effective ART adherence to maintain immune function and reduce the burden of cervical cancer. However, the study has a few limitations. First, as the participating women were enrolled in the urban Lagos metropolis with the exclusion of those living in the slums and suburban areas of Lagos, the study findings can only be these settings in Lagos. Secondly, due to the cross-sectional nature of the study, we are unable to infer causality inference in the observed associations between the identified factors and multiple HR-HPV infections. Finally, as the study was conducted in an HIV treatment centre where all the enrolled women were on combined ART, our findings may not be entirely representative of HIV-infected women who are not taking treatment.