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The Vaginal and Fecal Microbiota associated to cervical cancer development in a mice model.
1 , 1, 2 , 1 , 1 , 1, 3 , 1 , 1, 4 , 1 , 5 , 1 , * 1
1  Departamento de Genética y Biología Molecular, Cinvestav Unidad Zacatenco. Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, CDMX Código Postal 07360. Ciudad de México Tel: +52 (55) 5747 3800.
2  Present address: Division of Translational Medicine, Research Department, Sidra Medical and Research Institute, Doha, Qatar. email: [email protected]
3  Present address: The Novo Nordisk Foundation Center for Basic Metabolic Research. The University of Copenhagen. Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark. email: [email protected]
4  Present address: Biomédicos de Yucatán S.A de C.V. Calle 66 No. 466-A x 55 y 53, Centro, 97000 Mérida, Yuc. México. email: [email protected]
5  McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.


Introduction. Cervical cancer is an important health issue worldwide. Many factors are related to this condition as persistent human papillomavirus infection, the use of hormonal contraceptives, pH changes, and bacterial vaginosis. The association between the microbiota and cervical cancer is an interesting issue; given that environmental and hormonal factors changing the vaginal microbiota may contribute to cancer. Methods Using High-throughput DNA sequencing of V3-16S rDNA libraries, we determined the bacterial diversity in cervicovaginal lavages and fecal samples at different stages of cervical cancer development in the K14HPV16E7 mice model under +/- 17β-estradiol (E2) stimulus and compared it with an isogenic control (FVB). Results. We found that continuous E2 administration during 6 months in the model with type 16 E7 expression causing the development of cancer, is associated with significant changes in the microbiota diversity in the cervicovaginal lavages. Similar results were not observed in the model when no E2 was administered neither in the FVB mice. Comparable changes in the microbiota diversity of fecal samples were not observed. Conclusions. The persistent expression of E7 oncogene or the 17β-estradiol for longer periods of time, cause changes in the vaginal microbiota diversity and the cervical epithelium not necessarily leading to cervical cancer; however, the combined action of both, causes cervical carcinoma and defined changes in the abundance of bacterial taxa in the cervicovaginal lavages, suggesting a specific organ effect of E7 expression associated to E2 on the vaginal microbiota. Acknowledgments. Work supported by Cinvestav and CONACyT 163235 INFR-2011-01, FONSEC SS/IMSS/ISSSTE-CONACYT-233361, and CONACyT 0201904 grants.

Keywords: Cervicovaginal lavage; vaginal microbiota; fecal microbiota; cervical cancer; High-throughput DNA sequencing.