Role of cancer-associated fibroblasts in the progression of cervical cancer and its precancerous lesions: from phenotypic heterogeneity to epithelial-stromal positive feedback loops
Year: 2026
Type: article
Abstract: Persistent infection with high-risk human papillomavirus (HR-HPV) drives most cervical cancers, but only a minority of infected individuals develop invasive disease. This disparity suggests that host and tissue factors, including the local microenvironment, may influence progression. Cancer-associated fibroblasts (CAFs) are a prominent stromal population in cervical cancer, but their timing of activation, phenotypic diversity, and interactions with HPV-infected epithelium remain incompletely understood. This review summarizes reported CAF phenotypes and proposed cellular origins in cervical cancer and its precursor lesions. It evaluates evidence for epithelial–stromal signaling involving transforming growth factor-β (TGF-β), exosomal Wnt2B, and interleukin-6 (IL-6), as well as downstream CAF functions. Cross-sectional tissue and single-cell studies suggest that stromal fibroblast states differ between cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. These studies do not establish lineage relationships or show that fibroblast changes cause disease progression. We therefore propose a testable positive-feedback model of epithelial–stromal interactions, distinguishing cervical cancer-specific findings from mechanisms inferred from other tumors. Longitudinal sampling and cell-specific perturbation studies are needed to test this model and assess the clinical relevance of CAF-associated markers in precancerous lesions.
Source: Frontiers in Oncology
Institution: Yangtze University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225821917