Investigation of intravaginal practices as a factor associated with a high prevalence of genital human papillomavirus infection in adolescent girls.
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Background: Human papillomavirus (HPV) is a common sexually transmitted infection (STI) in women which mainly infects the mucosal areas. Young women are disproportionately infected by HPV, and factors that may render adolescents or younger women more vulnerable to HPV acquisition than older women have not been fully elucidated. This study aimed to investigate the associations between the prevalence of HPV, the use of intravaginal products, the immune activation status of cervical T cells, and alterations of the composition and concentrations of antimicrobial peptides (AMPs) in vaginal fluid among adolescent females close to their sexual debut and older women in KwaZulu-Natal. Methodology: Genital specimens (cervical cytobrush and cervicovaginal swabs) were collected from 154 female participants aged 14-19 and 25-35 years. From cervicovaginal swabs, HPV genotyping was done using a deoxyribonucleic acid (DNA) Flow hybridization system. Flow cytometry was conducted from cervical cytobrush specimens (evaluating CD38+, HLA-DR+, andCCR5+ expressions) to assess T-cell immune activation status. Enzyme-linked Immunosorbent Assay (ELISA) kits were used to measure genital concentrations of human β- defensin (HBD-1, HBD-2), and psoriasin from cervicovaginal swabs. Statistical tests conducted were Robust Poisson regression models (RPRM), the Tukey multiple comparison adjustment, t-test, and Mann Whitney U test. 𝑃 values of <0.05 were statistically significant. Results: HPV prevalence was 85%, with high-risk genotypes being the most prevalent. The majority of the cohort was infected with multiple genotypes (76.62%). Genotypes associated with cancer and current Gardasil®9 HPV vaccine targets were more common (53.9%) than those associated with genital warts (14.9%). The risk of HPV in adolescent females was 15.9% higher than in adult females. The use of vaginal inserted products (VIPs) was associated with a 40% higher risk of contracting genotypes related to cancer (p=0.0503) compared to nonusers. The risk of HPV infection for adolescents using VIPs was 23% higher than that of adults using VIPs. However, these differences were not statistically significant at a 5% level of significance. Sexual debut after 18 years significantly reduced the risk of overall HPV infection (p=0.0040) and infection with genotypes associated with cancer (p=0.0024). When comparing HPV infected adolescents and adults, the proportion of activated CD4+ T cells was significantly higher in adolescents, particularly in CD4+ HLA-DR+ cells (p=0.0008). CD8+ T cells showed no difference. A significantly higher concentration of HBD-2 was observed in HPV+ adults compared to HPV- adults (p=0.0215) and HPV+ adolescents (p=0.0189). Conclusion: The overall HPV prevalence is higher than the previously reported prevalence in KwaZulu-Natal province. In addition, we demonstrate that the use of VIPs may be associated with some HPV infection risk, particularly in adolescent females. This finding suggests that young women should be warned about the potential risk of using VIPs. We also confirm that the age-phase, delay in sexual debut, and the number of sexual life partners have significant associations with HPV genotypes linked to cancer, highlighting the importance and the urgency of vaccinating young girls with Gardasil®9 HPV vaccine. Adolescents with HPV have significantly higher levels of activated CD4+ T cells in their cervical mucosa, suggesting the presence of reactive activated cells that lack efficiency in the clearing of HPV infection in this age group. HPV infection upregulates HBD-2 levels during HPV infection, notably significantly higher in adult females than in adolescents. This investigation has generated new insights into the risk factors for HPV acquisition in young women. These findings need to be confirmed further by larger cohort size studies, essential for HPV prevention.