Background/Objectives: Infections by Human papillomaviruses (HPVs) are the most common sexually transmitted infections (STIs). Chronic infection by oncogenic HPVs are responsible for virtually all cervical cancer cases (the 4th most common neoplasm in women worldwide). In the recent years, prevalence of asymptomatic HPV anogenital infections has increased in middle-aged women (aged between 35 and 64 years), and the factors related to this trend are still unclear. Therefore, the aim of this study was to evaluate HPV prevalence and its associated factors in this population.

Methods: This cross-sectional study included 310 women aged 39-64 years from the INMA-Valencia and PAPILONG cohorts (recruitment: 2019-2023), covering a broad socioeconomic range, from middle-to-upper class to socially disadvantaged women, including female sex workers (FSWs). HPV detection for the INMA-Valencia cohort was performed at Arnau de Villanova Hospital using Roche Diagnostics technology, while samples from the PAPILONG cohort were analysed at the Clinical Hospital of Valencia using the Seegene Anyplex™ II HPV28 Detection assay. To ensure comparability across cohorts, all samples were blindly retested at the MIVEGEC laboratory using the LiPA25 genotyping assay. Data on sociodemographic, sexual and reproductive health, lifestyle, anthropometric and clinical factors were collected. To identify the determinants of HPV positivity, multivariable logistic regression models were fitted separately for the full sample (n = 310) and for FSWs (n = 49), given the increased HPV vulnerability of the latter.

Results: HPV prevalence was 20.3% in the overall population and 40.8% among FSW. Regarding the whole population, a positive statistically significant association was found between being HPV-positive and being at risk of poverty or social exclusion, having a history of STIs and vaginal douching and/or lubricant use. Conversely, being in a stable relationship was negatively associated. Regarding FSWs, being HPV-positive was statistically significant associated with older age, while higher body mass index was negatively associated.

Conclusions/Recommendations: HPV prevalence in our sample was greater in FSWs than in the overall population (40.8 vs. 20.3%). The most relevant determinants clustered in sociodemographic, clinical and lifestyle domains for the overall population, and sociodemographic and anthropometric factors for FSWs. These findings underscore the importance of studying HPV prevalence and its determinants in vulnerable populations, especially among FSWs.

Funding: EU-874583, GA-101128023, IDEAS19098LOPE, ESP21PI03, inv_cge_2022_04, inv_cge_2024_14, UGP-20-242, AICO/2021/182, CP20/0006, CD23/00090, MS21-133, MS21-125, CIACIF/2022/268, INVEST/2022/310, CIBERESP.