Background. The cervical cancer (CC) is given by HPV persistence due to the immunosuppressive tumor microenvironment generated by immunosuppressive cytokines1. It is known that the vaginal microbial ecosystem and the cytokine profile play a role in promoting cervical dysplasia2. Objectives. We assessed the association between cervical microbiota diversity and composition according to histopathological diagnosis of each stage of the natural history of CC, and evaluated IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-gmRNA expression levels in cervix across histopathological diagnosis and specific bacterial clusters.
Methods. We determined cervical microbiota by High-throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were evaluated. β-diversity analysis within histological diagnosis was carried out. Cytokine mRNA expression at the cervix level was analyzed across CST and histopathological diagnosis.
Results. We found a significant difference of microbiota diversity between non cervical lesions (NCL-HPV) negative vs cervical lesions (CL) and CC (p=0.006, p=0.036). When β-diversity was evaluated, the CC samples had the highest variation within groups (p<0.0006) and largest distance compared to NCL-HPV negative (p<0.00001). Predominant bacteria in women with normal cytology are L. crispatus and L. iners; Sneathia spp. in SIL and Fusobacterium spp. in CC. We found higher median levels of IL-4 and TGF-β1 mRNA at the cervix level, in CST dominated by Fusobacterium spp.
Conclusion. These results show that cervical microbiota may play a role in cervical cancer pathology and that HPV infection and the development of CL and CC are associated with changes in microbiota diversity and with cytokine expression patterns at the cervix level.
References. (1. Alcocer-González JM, Berumen J, Tamez-Guerra R, Gariglio P, Hernández-Pando R, Bermúdez-Morales VH, et al. In Vivo Expression of Immunosuppressive Cytokines in Human Papillomavirus-Transformed Cancer Cells. Viral Immunology 2006;19(3):481-91. 2. Behbakht K, Friedman J, Heimler I, Aroutcheva A, Simoes J and Faro S. Role of the vaginal microbiological ecosystem and cytokine profile in the promotion of cervical dysplasia: A case-control study. Infect Dis Obstet Gynecol 2002;10:181-6.)