Figure 2.

Major changes occur in the expression of genes and the cervical microenvironment as CIN I progress to CC. It has been observed that certain biomarkers of CCSCs exhibit increased expression and concentration levels, such as NANOG, SOX2 and KLF4, and there is also an increase in markers that are associated with CCSCs such as, CD133, Cd44, ALDH1, CK17, p63, CK8, NS, MSI1, CD49f, ABCG2, BMI1, PIWIL2 and LGR5. Many of these markers have been reported in other types of CSCs. In the cervical microenvironment, the complexity and quantity of the microbiota are altered. As the disease progresses, the genus Lactobacillus tends to disappear and instead, microorganisms as Fusobacterium sp., Sneathia sp., Pseudomonas and Streptococcus appear. CIN, cervical intraepithelial neoplasia; CC, cervical cancer; CCSCs, cervical cancer stem cells; CD, cluster of differentiation; CK, cytokeratin; NS, Nucleostemin; MSI1, musashi RNA binding protein 1; PIWIL2, piwi like RNA-mediated gene silencing 2; LGR5, Leucine-rich repeat-containing G-protein-coupled receptor 5; BMI1, BMI1 polycomb ring finger proto-oncogene; ABCG2, adenosine triphosphate-binding cassette subfamily G member 2; KLF4, Krüppel-like factor 4.