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The interplay between HPV, other sexually transmissible infections and genital microbiome on cervical microenvironment (MicroCervixHPV study)

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Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis to decipher this interaction with HPV takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes, and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through the Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. The neutrophil-to-lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevents the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The writing of this manuscript received the support of Fundação para a Ciência e a Tecnologia, Grant number UIDB/04295/2020, and doctoral scholarships (SFRH/BD/132900/2017). The authors acknowledge financial support from the Instituto de Investigação Científica Bento da Rocha Cabral, Clinical Analysis Laboratory Joaquim Chaves Saúde, Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa and Escola Superior de Tecnologia de Saúde de Lisboa, Instituto Politécnico de Lisboa.

Keywords

HPV Blood count ratios Cervical intra-epithelial neoplasia Cervical neoplasia Cervicovaginal microbiota Cytokines

Citation

Gonçalves-Nobre JG, Matos A, Carreira M, Veiga LC, Ginete C, Brito M, et al. The interplay between HPV, other sexually transmissible infections and genital microbiome on cervical microenvironment (MicroCervixHPV study). Front Cell Infect Microbiol. 2024;13:1251913.

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Frontiers Media

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