Genetic and transcriptomic analyses in a rare case of human papillomavirus-related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34462366", "kind": "science-record", "revision": 7, "content_hash": "sha256:087b318b3d25e29fea89132c421ca7071993d6a8e43d9ff927f126e5dc36ea36", "created_at": "2026-11-01T15:41:50Z", "updated_at": "2026-11-01T22:04:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genetic and transcriptomic analyses in a rare case of human papillomavirus-related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma.", "doi": "10.1101/mcs.a006102", "pmid": "34462366", "authors": ["Kuniaki Sato", "Kazuo Nishiyama", "Kenichi Taguchi", "Rina Jiromaru", "Hidetaka Yamamoto", "Akihide Matsunaga", "Ryozaburo Nagata", "Fumihide Rikimaru", "Satoshi Toh", "Yuichiro Higaki", "Shinya Oda", "Takashi Nakagawa", "Muneyuki Masuda"], "journal": "Cold Spring Harbor molecular case studies", "year": 2021, "abstract": "Human papillomavirus (HPV)-related oropharyngeal small-cell carcinoma (OPSmCC) is a rare malignancy with aggressive behavior, whereas HPV-related oropharyngeal squamous-cell carcinoma (OPSqCC) displays a favorable prognosis. Notably, these two malignancies occasionally arise in an identical tumor. In this case study, we explored the molecular characteristics that distinguishes these two carcinomas using a rare case of HPV-related oropharyngeal carcinoma (OPC) with the combined histology of SmCC and SqCC. Immunohistochemical analysis and HPV-RNA in situ hybridization (ISH) suggested that both SmCC and SqCC were HPV-related malignancies. Targeted exome sequencing revealed that SmCC and SqCC had no significant difference in mutations of known driver genes. In contrast, RNA sequencing followed by bioinformatic analyses suggested that aberrant transcriptional programs may be responsible for the neuroendocrine differentiation of HPV-related OPC. Compared to SqCC, genes up-regulated in SmCC were functionally enriched in inflammatory and immune responses (e.g., arachidonic acid metabolism). We then developed a SmCC-like gene module (top 10 up-regulated genes) and found that OPC patients with high module activity showed poor prognosis in The Cancer Genome Atlas (TCGA) and GSE65858 cohort. Gene set enrichment analysis of the SmCC-like gene module suggested its link to MYC proto-oncogene in the TCGA data set. Taken together, these findings suggest that the SmCC-like gene module may contribute to acquisition of aggressive phenotypes and tumor heterogeneity of HPV-related OPC. The present case study is the first report of genetic and transcriptomic aberrations in HPV-related OPSmCC combined with SqCC.", "claims": [{"id": "claim-method", "statement": "Overall survival curves were plotted according to the Kaplan–Meier method and compared by the log-rank test using the R package survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34462366", "locator": "sections[15] \"Analysis of the Publicly Available Transcriptomic Data Set\" paragraph 2", "quote": "Overall survival curves were plotted according to the Kaplan–Meier method and compared by the log-rank test using the R package survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA-seq data sets have been deposited into the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) with accession number GSE166773.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34462366", "locator": "sections[17] \"Database Deposition and Access\" paragraph 2", "quote": "The RNA-seq data sets have been deposited into the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) with accession number GSE166773."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34462366"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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