Single-cell Analysis Reveals Hpv-induced Keratinocyte Heterogeneity In Cervical Cancer

Cervical squamous compartment carcinoma (CESC), nan astir prevalent subtype of cervical cancer, remains a awesome world wellness load driven chiefly by persistent high-risk HPV infection and familial susceptibility.

A investigation squad led by Professor Ruozheng Wang, on pinch Mr. Peiwen Fan, Mr. Danning Dong, Dr. Yanning Feng and Dr. Xiaonan Zhu from nan Affiliated Tumor Hospital of Xinjiang Medical University, employed single-cell RNA sequencing (scRNA-seq) and multiplex immunohistochemistry (mIHC) to delineate nan molecular scenery of early-stage CESC. This activity sheds ray connected HPV-induced keratinocyte heterogeneity and tumor microenvironment (TME) remodeling during carcinogenesis, offering captious insights into therapeutic target discovery. The study was published successful nan Chinese Medical Journal connected October 20, 2025.

Single-cell RNA sequencing (scRNA-seq) of tumor and adjacent tissues from early-stage CESC patients identified a chopped organization of S100A7⁺PI3⁺ keratinocytes that were highly enriched successful tumors and intimately associated pinch HPV infection. Prognostic validation utilizing nan TCGA dataset showed that accrued infiltration of these cells was importantly correlated pinch poorer diligent outcomes. Within tumors, PI3⁺S100A7⁺ keratinocytes were recovered successful adjacent spatial proximity to CD163⁺ macrophages, engaging successful interactions that co-activated cardinal oncogenic pathways, including NF-κB, TNF signaling, and cytokine–receptor interactions. These signaling networks collectively promoted tumor proliferation, differentiation, and metastasis. Notably, patients pinch precocious infiltration of some compartment types exhibited markedly reduced wide survival.

Fibroblast subtyping further revealed 4 chopped populations. Among these, cancer-associated fibroblasts (CAFs; C1 subtype) were predominant successful tumor tissues and displayed beardown activation of inflammatory pathways, whereas undifferentiated fibroblasts (C3 subtype) were much abundant successful adjacent non-cancerous tissues.

Prof. Wang quoted, "We identified PI3 and S100A7 arsenic importantly overexpressed successful HPV-positive cervical squamous compartment carcinoma samples compared to non-tumor controls, arsenic validated by TCGA data. Through immunohistochemistry, we further confirmed nan co-localization of S100A7 and PI3 wrong keratinocytes, defining a chopped subpopulation of PI3+S100A7+ cells."

Prof. Wang further highlighted that these interactions betwixt keratinocytes and immune cells are pivotal successful shaping nan tumor environment: "Macrophages were enriched successful tumor tissues and exhibited beardown crosstalk pinch keratinocytes, mediated by TNF, CCL2, CXCL8, and IL10."

The study sheds ray connected really HPV infection drives transcriptional reprogramming successful keratinocytes, creating a permissive tumor microenvironment done intricate stromal–immune crosstalk. This system apt underlies some viral persistence and nan early stages of malignant transformation.

This investigation not only deepens our knowing of cervical carcinogenesis but besides reveals imaginable therapeutic targets for halting illness progression by dissecting nan cross-talk betwixt HPV-infected keratinocytes, immune cells, and stromal components successful early CESC. Future investigations focusing connected pathway-specific inhibitors aliases immunomodulatory agents directed astatine these compartment populations could fundamentally toggle shape nan guidance of early-stage CESC.

In conclusion, this find represents a pivotal measurement toward precision medicine successful cervical cancer-redefining really HPV-driven cellular reprogramming is understood and opening nan doorway to earlier, much effective therapeutic interventions.