Deciphering the cellular and molecular landscape of cervical cancer progression through single-cell and spatial transcriptomics

Cervical cancer represents a significant global health challenge, with complex cellular and molecular mechanisms driving its progression from HPV infection to invasive malignancy. This study employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (stRNA-seq) to comprehensively characterize the tumor microenvironment (TME) across different stages of cervical cancer development. Through analysis of samples from normal cervix, HPV-infected normal cervix, high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer, we identified distinct cellular populations and their dynamic changes during disease progression. Our findings revealed significant heterogeneity in immune cell populations, particularly highlighting the role of SPP1+ macrophages that were substantially enriched in cervical cancer compared to precancerous and normal tissues. Cell-cell communication networks and spatial mapping demonstrated that SPP1+ macrophages interact extensively with immune cells through the SPP1-CD44 signaling axis. This interaction contributes to an immunosuppressive microenvironment through modulation of T cell function and promotion of tumor cell survival. Furthermore, high expression of SPP1 correlated with advanced tumor stages and poor overall survival in cervical cancer patients, highlighting its potential as a prognostic biomarker. Our comprehensive characterization of the cellular landscape and intercellular communication networks in cervical cancer progression provides valuable insights for the development of targeted therapeutic strategies aimed at modulating the TME, particularly through disruption of the SPP1-CD44 axis. These findings establish a foundation for more effective personalized approaches to improve clinical outcomes in cervical cancer patients.