Single-Cell Landscape Change in Cervical Epithelial Cells and Microenvironment During the Transformation from CINIII to Cervical Squamous Cell Carcinoma

Background: The rising incidence of CINIII, particularly in younger patients, has highlighted limitations of current surgical treatments, which can affect fertility and carry recurrence risks. This underscores an urgent clinical need for non-invasive therapies. Our study addresses this by investigating the cellular and molecular changes during CINIII progression to cervical squamous cell carcinoma (CSCC). Methods: We employed single-cell sequencing to meticulously analyze cell types and molecular mechanisms within cervical epithelial cells and their microenvironment throughout the CINIII-to-CSCC transition. Results: Key findings include the identification of Sox2 and its signaling pathway as markers for specific cervical stem cells (CCSCs) during malignant transformation. In the microenvironment, upregulated VWF, MMP2, and HTRA1 were observed in vascular endothelial cells, while TXNIP+ and ARL4D+ fibroblasts underwent transformation into myofibroblasts. Immune cell proportions notably increased, particularly macrophages, T cells, B cells, NK cells, mast cells, and neutrophils, contrasting with a decrease in non-immune cells. Furthermore, interaction analysis revealed that communication between macrophages and cervical epithelial cells was the most prominent. Conclusions: This research comprehensively details the complex cellular and molecular remodeling inherent in CINIII progression. By pinpointing specific pathways and cell populations, our findings establish a crucial framework for developing innovative, non-invasive drug therapies to delay disease progression and ultimately improve long-term reproductive outcomes for patients.