{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:41:44Z","timestamp":1787568104415,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":235,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016692","name":"Key Research and Development Program of Ningxia","doi-asserted-by":"publisher","award":["2023BEG03048"],"award-info":[{"award-number":["2023BEG03048"]}],"id":[{"id":"10.13039\/100016692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Analytical Cellular Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human papillomavirus (HPV) infection is a major contributor to cervical cancer (CC), yet the molecular mechanisms driving HPV\u2010associated immune evasion remain largely undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk RNA\u2010seq (The Cancer Genome Atlas [TCGA]\u2013CESC) and single\u2010cell RNA\u2010seq datasets (GSE171894, GSE197461) were analyzed to elucidate transcriptional and immune landscape differences between HPV\u2010positive and HPV\u2010negative cervical tumors. Differentially expressed genes (DEGs) were identified using DESeq2. Functional enrichment analyses were conducted through gene set enrichment analysis (GSEA), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) methodologies. Immune evasion feature genes were selected employing LASSO, Random Forest, and SVM\u2010RFE techniques. Regulatory networks for transcription factors and miRNAs were constructed. Immune infiltration was evaluated using CIBERSORT and ssGSEA. Validation of key signature genes was performed in CC cell lines (HeLa, SiHa, C33A, and W12) via real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR) and Western blot. The functional roles of IFNGR1 were examined through siRNA\u2010mediated knockdown, complemented by CCK\u20108, colony formation, Transwell migration\/invasion, and flow cytometry apoptosis assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 6266 DEGs effectively differentiated HPV\u2010positive from HPV\u2010negative tumors. HPV\u2010positive tumors exhibited enrichment in viral infection and immune response pathways, while HPV\u2010negative tumors demonstrated activation of oncogenic signaling. Machine learning algorithms identified IFNGR1, TRADD, and PSMB9 as immune evasion feature genes associated with HPV. Regulatory network analysis emphasized IRF1\/IRF2 and several miRNAs as critical modulators. Immune infiltration analysis indicated increased infiltration of Dendritic and Plasma cells in HPV\u2010positive tumors, correlating with TRADD expression. Kaplan\u2010Meier analysis further showed a trend toward worse overall survival among HPV\u2010positive patients with high IFNGR1 expression (hazard ratio [HR]\u2009=\u20091.78, 95% confidence interval [CI]: 0.86\u20133.68; log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      = 0.113). Notably, IFNGR1 was significantly upregulated in HPV\u2010positive CC cell lines at both mRNA and protein levels. IFNGR1 knockdown markedly inhibited proliferation, colony formation, migration, and invasion, while enhancing apoptosis in HeLa and SiHa cells, thereby confirming its essential role in the progression of HPV\u2010associated CC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified IFNGR1 as a key immune evasion\u2010related gene in HPV\u2010positive CC, elucidating its regulatory network and functional contributions, while positioning it as a potential therapeutic target for HPV\u2010associated tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ancp\/6756766","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:14:37Z","timestamp":1787566477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering HPV\u2010Associated Immune Evasion in Cervical Cancer Through Multi\u2010Omics Profiling and Computational Screening"],"prefix":"10.1155","volume":"2026","author":[{"given":"Rui","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5609-2698","authenticated-orcid":false,"given":"Na","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_12_1_2","article-title":"Breast Cancer Epidemiology and Clinical Outcomes in Moroccan Women: A 6-Year Retrospective Study","volume":"49","author":"Aboulhoda F.","year":"2025","journal-title":"Pan African Medical Journal"},{"key":"e_1_2_12_2_2","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.31557\/APJCP.2025.26.6.2129","article-title":"Exploring the Potential of a Novel Oil Blend Therapy for Immunity Enhancement and Cervical Carcinoma Treatment","volume":"26","author":"Dunjic M.","year":"2025","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"e_1_2_12_3_2","first-page":"353","article-title":"Integration of Portable PCR and a Lateral Flow Assay for the Rapid Detection of HPV Type 16","volume":"18","author":"Yusuf M.","year":"2025","journal-title":"Medical Devices: Evidence and Research"},{"key":"e_1_2_12_4_2","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.758337","article-title":"Cervical Cancer, Papillomavirus, and miRNA Dysfunction","volume":"8","author":"Ba\u00f1uelos-Villegas E. G.","year":"2021","journal-title":"Frontiers in Molecular Biosciences"},{"key":"e_1_2_12_5_2","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2024.1394902","article-title":"Identification of an Inflammatory Response-Related Gene Prognostic Signature and Immune Microenvironment for Cervical Cancer","volume":"11","author":"Wu Z.","year":"2024","journal-title":"Frontiers in Molecular Biosciences"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.6995"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103675"},{"key":"e_1_2_12_8_2","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.993785","article-title":"Diabetes Associated With Cervical Carcinoma Among High-Risk HPV-Infected Patients With Cytologically Diagnosed High Grade Squamous Intraepithelial Lesion","volume":"13","author":"Yue C.","year":"2022","journal-title":"Frontiers in Endocrinology"},{"key":"e_1_2_12_9_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.5483\/BMBRep.2022.55.9.042","article-title":"Untold Story of Human Cervical Cancers: HPV-Negative Cervical Cancer","volume":"55","author":"Lee L.","year":"2022","journal-title":"BMB Reports"},{"key":"e_1_2_12_10_2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1645019","article-title":"HPV Infection and the Immune Microenvironment in Cervical Cancer","volume":"16","author":"Li Y.","year":"2025","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_12_11_2","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3892\/ol.2015.2884","article-title":"Link Between Chronic Inflammation and Human Papillomavirus-Induced Carcinogenesis (Review)","volume":"9","author":"Fernandes J. V.","year":"2015","journal-title":"Oncology Letters"},{"key":"e_1_2_12_12_2","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15153849","article-title":"Tumor Immune Microenvironment in Gynecologic Cancers","volume":"15","author":"Margul D.","year":"2023","journal-title":"Cancers"},{"key":"e_1_2_12_13_2","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-025-06896-3","article-title":"Targeting Immune Microenvironment in Cervical Cancer: Current Research and Advances","volume":"23","author":"Zhang Z.","year":"2025","journal-title":"Journal of Translational Medicine"},{"key":"e_1_2_12_14_2","first-page":"1524","article-title":"Correlation of CXCL12 Expression and FoxP3+ Cell Infiltration With Human Papillomavirus Infection and Clinicopathological Progression of Cervical Cancer","volume":"175","author":"Jiang Y.","year":"2009","journal-title":"American Journal of Pathology"},{"key":"e_1_2_12_15_2","first-page":"655","article-title":"Alterations of T-Cell Surface Markers in Older Women With Persistent Human Papillomavirus Infection","volume":"128","author":"Rector A.","year":"2010","journal-title":"International Journal of Cancer"},{"key":"e_1_2_12_16_2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26189214","article-title":"From Viral Infection to Genome Reshaping: The Triggering Role of HPV Integration in Cervical Cancer","volume":"26","author":"Li J.","year":"2025","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_12_17_2","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.814169","article-title":"The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-\u03b2 and PD-L1 Pathways","volume":"12","author":"Birrer M. J.","year":"2022","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_12_18_2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241713646","article-title":"Ficus carica Latex Modulates Immunity-Linked Gene Expression in Human Papillomavirus Positive Cervical Cancer Cell Lines: Evidence From RNA Seq Transcriptome Analysis","volume":"24","author":"Cakir M. O.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_12_19_2","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.02203-24","article-title":"The Retinoblastoma Protein Contributes to Maintaining the Stability of HPV E7 in Cervical Cancer Cells","volume":"99","author":"Gbala I.","year":"2025","journal-title":"Journal of Virology"},{"key":"e_1_2_12_20_2","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/123010","article-title":"NTPDase5\/PCPH as a New Target in Highly Aggressive Tumors: A Systematic Review","volume":"2014","author":"Bracco P. A.","year":"2014","journal-title":"BioMed Research International"},{"key":"e_1_2_12_21_2","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.537650","article-title":"Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns","volume":"10","author":"Aggarwal N.","year":"2020","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"key":"e_1_2_12_22_2","doi-asserted-by":"crossref","first-page":"6881","DOI":"10.1002\/cam4.4054","article-title":"Identification of a Novel Six-Gene Signature With Potential Prognostic and Therapeutic Value in Cervical Cancer","volume":"10","author":"Qu X.","year":"2021","journal-title":"Cancer Medicine"},{"key":"e_1_2_12_23_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.critrevonc.2021.103310","article-title":"Long Non-Coding RNAs Regulate the Hallmarks of Cancer in HPV-Induced Malignancies","volume":"161","author":"Dias T. R.","year":"2021","journal-title":"Critical Reviews in Oncology\/Hematology"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21386"},{"key":"e_1_2_12_26_2","unstructured":"LoveM. AndersS. andHuberW. Differential Analysis of Count Data\u2013The deseq2 Package 2014."},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01020-z"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1057\/9780230509993"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05083-x"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9501.2"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4091"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0654-x"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw777"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2746-2"},{"key":"e_1_2_12_37_2","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-021-02942-0","article-title":"Comprehensive Multiomic Characterization of Human Papillomavirus-Driven Recurrent Respiratory Papillomatosis Reveals Distinct Molecular Subtypes","volume":"4","author":"Sievers C.","year":"2021","journal-title":"Communications Biology"},{"key":"e_1_2_12_38_2","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1007\/s12250-021-00413-8","article-title":"Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care","volume":"36","author":"Dong H.","year":"2021","journal-title":"Virologica Sinica"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1673665"},{"key":"e_1_2_12_40_2","first-page":"309","article-title":"CagA Increases DNA Methylation and Decreases PTEN Expression in Human Gastric Cancer","volume":"19","author":"Zhang B.","year":"2018","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_12_41_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108410","article-title":"MiR-122 Directly Inhibits Human Papillomavirus E6 Gene and Enhances Interferon Signaling Through Blocking Suppressor of Cytokine Signaling 1 in SiHa Cells","volume":"9","author":"He J.","year":"2014","journal-title":"PLoS One"},{"key":"e_1_2_12_42_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109790","article-title":"IFI16 Promotes Cervical Cancer Progression by Upregulating PD-L1 in Immunomicroenvironment Through STING-TBK1-NF-kB Pathway","volume":"123","author":"Cai H.","year":"2020","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"e_1_2_12_43_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/1389202916666141223220551","article-title":"Genetics and Vaccines in the Era of Personalized Medicine","volume":"16","author":"Castiblanco J.","year":"2015","journal-title":"Current Genomics"},{"key":"e_1_2_12_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.673838"},{"key":"e_1_2_12_45_2","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S399874"},{"key":"e_1_2_12_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13030564"},{"key":"e_1_2_12_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar4526"},{"key":"e_1_2_12_48_2","article-title":"MKRN1 Regulates the Expression Profiles and Transcription Factor Activity in HeLa Cells Inhibition Suppresses Cervical Cancer Cell Progression","volume":"14","author":"Xiang D.","year":"2024","journal-title":"Scientific Reports"},{"key":"e_1_2_12_49_2","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-95718-9","article-title":"Comprehensive Analysis of Immune Cell Enrichment in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma","volume":"11","author":"Mito I.","year":"2021","journal-title":"Scientific Reports"},{"key":"e_1_2_12_50_2","doi-asserted-by":"crossref","DOI":"10.1038\/s41525-024-00418-8","article-title":"Structure and Transcription of Integrated HPV DNA in Vulvar Carcinomas","volume":"9","author":"Van Arsdale A.","year":"2024","journal-title":"npj Genomic Medicine"},{"key":"e_1_2_12_51_2","doi-asserted-by":"crossref","first-page":"25050","DOI":"10.18632\/oncotarget.7732","article-title":"Squamous Cell Carcinomas of the Lung and of the Head and Neck: New Insights on Molecular Characterization","volume":"7","author":"Polo V.","year":"2016","journal-title":"Oncotarget"},{"key":"e_1_2_12_52_2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1080\/10409238.2016.1226250","article-title":"Diverse Mechanisms Evolved by DNA Viruses to Inhibit Early Host Defenses","volume":"51","author":"Crow M. S.","year":"2016","journal-title":"Critical Reviews in Biochemistry and Molecular Biology"}],"container-title":["Analytical Cellular Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ancp\/6756766","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ancp\/6756766","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ancp\/6756766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:14:43Z","timestamp":1787566483000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ancp\/6756766"}},"subtitle":[],"editor":[{"given":"Andrey","family":"Elchaninov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/ancp\/6756766"],"URL":"https:\/\/doi.org\/10.1155\/ancp\/6756766","archive":["Portico"],"relation":{},"ISSN":["2210-7177","2210-7185"],"issn-type":[{"value":"2210-7177","type":"print"},{"value":"2210-7185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6756766"}}