Cervical Squamous Intraepithelial Lesions are Associated with Changes in the Vaginal Microbiota of Mexican Women

Nieves-Ramirez, M.; Partida-Rodriguez, O.; Moran-Silva, P.; Serrano-Vazquez, A.; Perez-Juarez, H.; Perez-Rodriguez, M. E.; Arrieta, M. C.; Ximenez-Garcia, C.; Finlay, B. B.

doi:10.1101/2021.02.23.432613

bioRxiv · 10.1101/2021.02.23.432613

Cervical Squamous Intraepithelial Lesions are Associated with Changes in the Vaginal Microbiota of Mexican Women

Nieves-Ramirez, M.·Partida-Rodriguez, O.·Moran-Silva, P.·Serrano-Vazquez, A.·Perez-Juarez, H.·Perez-Rodriguez, M. E.·Arrieta, M. C.·Ximenez-Garcia, C.·Finlay, B. B.

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Abstract

Cervical cancer is an important health concern worldwide and is one of the leading causes of deaths in Mexican women. Previous studies have shown changes in the female genital tract microbe community related to Human Papillomavirus (HPV) infection and cervical cancer, yet this link remains unexplored in many human populations. This study evaluated the vaginal bacterial community among Mexican women with pre-cancerous Squamous Intraepithelial Lesions (SIL). We sequenced the V3 region of the 16S rRNA gene (Illumina Miseq) in cervical samples from 300 Mexican women, including 157 patients with SIL, most of which were HPV positive, and 143 healthy women without HPV infection or SIL. Beta-diversity analysis showed that 14.6% of the variance in vaginal bacterial community structure is related to the presence of SIL. Presence of SIL was also associated with a higher species richness (Chao 1). MaAsLiN analysis yielded independent associations between SIL/HPV status and an increase in the relative abundance Brachybacterium conglomeratum, as well as a decrease in Sphingobium yanoikuyae and Lactobacillus spp. We also identified independent associations between HPV-16, the most common HPV subtype linked to SIL, and Brachybacterium conglomeratum. Our work indicates that the presence of SIL and HPV infection is associated with important changes in the vaginal microbiome, some of which may be specific to this human population. IMPORTANCEHPV plays a critical role in cervical carcinogenesis but is not sufficient for cervical cancer development, indicating involvement of other factors. Vaginal microbiota is an important factor in controlling infections caused by HPV and depending on its composition it can modulate the microenvironment in vaginal mucosa against viral infection. Ethnic and sociodemographic factors influence differences in vaginal microbiome composition, which underlies the dysbiotic patterns linked to HPV infection and cervical cancer across different women populations. Here, we provide evidence for associations between vaginal microbiota patterns and HPV infection, linked to ethnic and sociodemographic factor. To our knowledge, this is the first report of Brevibacterium aureum and Brachybacterium conglomeratum species linked to HPV infection or SIL.

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Nieves-Ramirez, M., Partida-Rodriguez, O., Moran-Silva, P., Serrano-Vazquez, A., Perez-Juarez, H., Perez-Rodriguez, M. E., Arrieta, M. C., Ximenez-Garcia, C., Finlay, B. B.. 2021-02-25. Cervical Squamous Intraepithelial Lesions are Associated with Changes in the Vaginal Microbiota of Mexican Women. https://doi.org/10.1101/2021.02.23.432613

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