HIV与HPV共感染在波多黎各HIV感染者口腔真菌组失调中的协同效应

Background : Despite advances in suppressive antiretroviral therapy, people with HIV (PWH) have a higher prevalence of HPV infection than people without HIV (PWOH), suggesting that other factors independent of HIV may be contributing to increased susceptibility of HPV infections in PWH. The human mycobiome (fungal communities of the microbiome) can play an important role in immune modulation, promoting activation of inflammatory pathways and the production of carcinogenic organic compounds. Non-medical factors such as oral HPV infections, can induce oral mycobiome community-level shifts which may facilitate oncogenesis, but it has not been evaluated in the context of HIV in PR. In this study, we evaluated the prevalence of oral HPV infection and chracterized the oral mycobiome in Puerto Rican PWH and PWOH with and without coinfection with oral HPV (HPV+ vs HPV-). Methods : Saliva and oral rinse samples were collected from 132 sexually active individuals (PWH vs PWOH). Oral rinse samples were analyzed for HPV infection and genotype using the DNA ELISA kit HPV SPF10 and RHA kit HPV SPF10-LiPA25. Extracted DNA from saliva was used to sequence the ITS and characterize the oral mycobiome. Oral mycobiome was analyzed using Shannon index for diversity and Pielou index for evenness using QIIME2 and R-statistical software. Results : The overall prevalence of oral HPV infection among participants of the study was 33%. The prevalence of oral HPV infection was 3x higher in PWH (44%) compared to PWOH (14%). Considering all HPV+ genotypes 47% were high-risk for cancer development (PWH= 95% vs PWOH= 5%). On the other hand, fungal diversity was significantly lower in PWH compared to PWOH (p= 0.038), while fungal diversity (p= 0.020) and evenness (p= 0.088) was lower in HPV+ individuals compared to HPV- individuals. Furthermore, HPV+ PWH showed significantly lower fungal diversity (p= 0.048) and evenness (p= 0.087) compared to HPV- PWOH. Moreover, PWH had significantly higher abundance of genus Candida than PWOH (p= 0.048). HPV+ PWH had significantly higher relative abundance of Candida in saliva (p= 0.007). Conclusion : Higher prevalence of oral HPV infection was observed in PWH in comparison to PWOH in PR. Dysbiosis of the oral mycobiome was observed in both HIV and oral HPV infection, however independent of HIV status, HPV+ individuals had lower oral fungal species evenness. Moreover, Candida abundance levels were significantly higher in coinfection of HIV and HPV, indicating that the oral mycobiome may be potentially influenced by a synergistic effect caused by the coinfection. Overall, these findings suggest that HPV status greatly impacts oral mycobiome homeostasis that can potentially contribute to the natural history of HPV and increased cancer risk. Understanding the interplay between viral infections and the oral mycobiome may explain clinical disparities regarding the natural history of HPV in PR.