biostudies-literatureWang XYunnan Fundamental Research ProjectsYunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Project on Applied Basic ResearchYunnan Provincial Key Laboratory of Clinical Virology Open Project417https://www.ebi.ac.uk/biostudies/studies/S-EPMC12628552biostudies-literatureUnknown25(1)<h4>Background</h4>Human papillomavirus (HPV) infection is associated with an increased risk of cutaneous squamous cell carcinoma (CSCC). A comprehensive understanding of the cellular heterogeneity of HPV-positive and -negative CSCC is crucial for improving diagnosis and preventing tumor progression.<h4>Methods</h4>We conducted an integrated analysis of single-cell RNA and spatial transcriptomic data from different skin tissue sources to map the cellular landscape of the tumor microenvironment (TME) in both HPV positive and negative CSCC. Results were validated through multiplex immunohistochemistry (mIHC) and in vitro experiments.<h4>Results</h4>We identified 10 major cell types in CSCC and normal skin samples, including epithelial cells, myeloid cells, T cells, fibroblasts, endothelial cCancer cell internationalMulti-omics analysis unveils the role of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.PMC12628552202401AT070051202201AY070001-251202205AG070061-BD-02Xu LGuan ZLi CLi TChen JZhang JXinYangJin MTao SWang XJin YAo CfalseMulti-omics analysis unveils the role of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.<h4>Background</h4>Human papillomavirus (HPV) infection is associated with an increased risk of cutaneous squamous cell carcinoma (CSCC). A comprehensive understanding of the cellular heterogeneity of HPV-positive and -negative CSCC is crucial for improving diagnosis and preventing tumor progression.<h4>Methods</h4>We conducted an integrated analysis of single-cell RNA and spatial transcriptomic data from different skin tissue sources to map the cellular landscape of the tumor microenvironment (TME) in both HPV positive and negative CSCC. Results were validated through multiplex immunohistochemistry (mIHC) and in vitro experiments.<h4>Results</h4>We identified 10 major cell types in CSCC and normal skin samples, including epithelial cells, myeloid cells, T cells, fibroblasts, endothelial c2025-01-01T00:00:00Z2025 Nov2026-06-06T15:00:55.272Z2026-06-01T03:10:29.388ZS-EPMC126285524125786210.1186/s12935-025-04061-w