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We performed single\u2010cell RNA sequencing and whole\u2010exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection\u2010related features, and gene expression profiles of SCNEC of the cervix at single\u2010cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA\u2010seq data from external cervical neuroendocrine cancer. Furthermore, sex\u2010determining region Y\u2010box\u20092 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV\u2010infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high\u2010risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small\u2010cell neuroendocrine tumorigenesis in the cervix.<\/jats:p>","DOI":"10.1002\/jmv.70183","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T10:17:26Z","timestamp":1737368246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Small\u2010Cell Neuroendocrine Carcinoma of the Cervix"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8666-6924","authenticated-orcid":false,"given":"Xinyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing Maternal and Child Health Care Hospital Beijing P. R. 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