{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:27:53Z","timestamp":1792517273832,"version":"4.5.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":42,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00338555"],"award-info":[{"award-number":["RS-2024-00338555"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00275813, RS-2025-00557349"],"award-info":[{"award-number":["RS-2023-00275813, RS-2025-00557349"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005006","name":"Asan Institute for Life Sciences, Asan Medical Center","doi-asserted-by":"publisher","award":["2022IP0046, 2023IP0083-2 and 2024IP0082-1"],"award-info":[{"award-number":["2022IP0046, 2023IP0083-2 and 2024IP0082-1"]}],"id":[{"id":"10.13039\/501100005006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HR21C0198"],"award-info":[{"award-number":["HR21C0198"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08082-5","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T15:53:53Z","timestamp":1775490833000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intratumoral spatiotemporal heterogeneity of HPV DNA status in HPV-associated oropharyngeal squamous cell carcinoma with clinical record"],"prefix":"10.1186","volume":"24","author":[{"given":"Bokyung","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Won","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Seon","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonkyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Se","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ho","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Yuhl","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Yoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hye","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Gwang","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Eun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-456X","authenticated-orcid":false,"given":"Chang Ohk","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ja","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"8082_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/jnci\/92.9.709","volume":"92","author":"ML Gillison","year":"2000","unstructured":"Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709\u201320.","journal-title":"J Natl Cancer Inst"},{"key":"8082_CR2","first-page":"S44","volume":"30","author":"JS Lewis","year":"2017","unstructured":"Lewis JS. Morphologic diversity in human papillomavirus-related oropharyngeal squamous cell carcinoma. Catch Me If You Can! Mod Pathol. 2017;30:S44\u201353.","journal-title":"Catch Me If You Can! Mod Pathol"},{"issue":"Pt 1","key":"8082_CR3","first-page":"111","volume":"185","author":"ME Perry","year":"1994","unstructured":"Perry ME. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance. J Anat. 1994;185(Pt 1):111\u201327.","journal-title":"J Anat"},{"key":"8082_CR4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.radonc.2017.10.018","volume":"126","author":"P Lassen","year":"2018","unstructured":"Lassen P, Lacas B, Pignon JP, Trotti A, Zackrisson B, Zhang Q, Overgaard J, Blanchard P. Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project. Radiother Oncol. 2018;126:107\u201315.","journal-title":"Radiother Oncol"},{"key":"8082_CR5","doi-asserted-by":"publisher","first-page":"104522","DOI":"10.1016\/j.oraloncology.2019.104522","volume":"101","author":"C Fakhry","year":"2020","unstructured":"Fakhry C, Waterboer T, Westra WH, Rooper LM, Windon M, Troy T, Koch W, Gourin CG, Bender N, Yavvari S, Kiess AP, Miles BA, Ryan WR, Ha PK, Eisele DW, D\u2019Souza G. Distinct biomarker and behavioral profiles of human papillomavirus-related oropharynx cancer patients by age. Oral Oncol. 2020;101:104522\u2013104522.","journal-title":"Oral Oncol"},{"key":"8082_CR6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa0912217","volume":"363","author":"KK Ang","year":"2010","unstructured":"Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-T\u00e2n PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24\u201335.","journal-title":"N Engl J Med"},{"key":"8082_CR7","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1038\/s41388-023-02819-y","volume":"42","author":"YX Lim","year":"2023","unstructured":"Lim YX, Mierzwa ML, Sartor MA, D\u2019Silva NJ. Clinical, morphologic and molecular heterogeneity of HPV-associated oropharyngeal cancer. Oncogene. 2023;42:2939\u201355.","journal-title":"Oncogene"},{"key":"8082_CR8","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1126\/science.1208130","volume":"333","author":"N Stransky","year":"2011","unstructured":"Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cort\u00e9s ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escare\u00f1o C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157\u201360.","journal-title":"Science"},{"key":"8082_CR9","doi-asserted-by":"publisher","first-page":"7094","DOI":"10.1038\/sj.onc.1208854","volume":"24","author":"C Rosty","year":"2005","unstructured":"Rosty C, Sheffer M, Tsafrir D, Stransky N, Tsafrir I, Peter M, de Cr\u00e9moux P, de La Rochefordi\u00e8re A, Salmon R, Dorval T, Thiery JP, Couturier J, Radvanyi F, Domany E, Sastre-Garau X. Identification of a proliferation gene cluster associated with HPV E6\/E7 expression level and viral DNA load in invasive cervical carcinoma. Oncogene. 2005;24:7094\u2013104.","journal-title":"Oncogene"},{"key":"8082_CR10","doi-asserted-by":"crossref","unstructured":"Sastre-Garau X, Harl\u00e9 A. Pathology of HPV-Associated Head and Neck Carcinomas: Recent Data and Perspectives for the Development of Specific Tumor Markers. Front Oncol. 2020;10.","DOI":"10.3389\/fonc.2020.528957"},{"key":"8082_CR11","volume-title":"AJCC cancer staging manual","year":"2017","unstructured":"Amin MB, Greene ES FL, editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.","edition":"8"},{"key":"8082_CR12","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1631\/jzus.B2000161","volume":"21","author":"FH Fauzi","year":"2020","unstructured":"Fauzi FH, Hamzan NI, Rahman NA, Suraiya S, Mohamad S. Detection of human papillomavirus in oropharyngeal squamous cell carcinoma. J Zhejiang Univ Sci B. 2020;21:961\u201376.","journal-title":"J Zhejiang Univ Sci B"},{"key":"8082_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.6004\/jnccn.2022.0016","volume":"20","author":"JJ Caudell","year":"2022","unstructured":"Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, Birkeland AC, Brizel DM, Busse PM, Cmelak AJ, Colevas AD, Eisele DW, Galloway T, Geiger JL, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Mell LK, Mittal BB, Pinto HA, Rocco JW, Rodriguez CP, Savvides PS, Schwartz D, Shah JP, Sher D, St John M, Weber RS, Weinstein G, Worden F, Yang Bruce J, Yom SS, Zhen W, Burns JL, Darlow SD. NCCN Guidelines\u00ae Insights: Head and Neck Cancers, Version 1.2022. J Natl Compr Canc Netw. 2022;20:224\u201334.","journal-title":"J Natl Compr Canc Netw"},{"key":"8082_CR14","doi-asserted-by":"publisher","first-page":"138469","DOI":"10.4061\/2011\/138469","volume":"2011","author":"RL Cantley","year":"2011","unstructured":"Cantley RL, Gabrielli E, Montebelli F, Cimbaluk D, Gattuso P, Petruzzelli G. Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review. Pathol Res Int. 2011;2011:138469.","journal-title":"Pathol Res Int"},{"key":"8082_CR15","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1038\/modpathol.2015.113","volume":"28","author":"H Mirghani","year":"2015","unstructured":"Mirghani H, Casiraghi O, Amen F, He M, Ma XJ, Saulnier P, Lacroix L, Drusch F, Ben Lakdhar A, Saint Guily JL, Badoual C, Scoazec JY, Vielh P. Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice. Mod Pathol. 2015;28:1518\u201327.","journal-title":"Mod Pathol"},{"key":"8082_CR16","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1002\/ijc.28580","volume":"134","author":"MM Rietbergen","year":"2014","unstructured":"Rietbergen MM, Snijders PJ, Beekzada D, Braakhuis BJ, Brink A, Heideman DA, Hesselink AT, Witte BI, Bloemena E, Baatenburg-De Jong RJ, Leemans CR, Brakenhoff RH. Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas. Int J Cancer. 2014;134:2366\u201372.","journal-title":"Int J Cancer"},{"key":"8082_CR17","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1097\/PAS.0b013e3181e84652","volume":"34","author":"JS Lewis","year":"2010","unstructured":"Lewis JS Jr., Thorstad WL, Chernock RD, Haughey BH, Yip JH, Zhang Q, El-Mofty SK. p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34:1088\u201396.","journal-title":"Am J Surg Pathol"},{"key":"8082_CR18","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/s41588-023-01357-3","volume":"55","author":"SV Puram","year":"2023","unstructured":"Puram SV, Mints M, Pal A, Qi Z, Reeb A, Gelev K, Barrett TF, Gerndt S, Liu P, Parikh AS, Ramadan S, Law T, Mroz EA, Rocco JW, Adkins D, Thorstad WL, Gay HA, Ding L, Paniello RC, Pipkorn P, Jackson RS, Wang X, Mazul A, Chernock R, Zevallos JP, Silva-Fisher J, Tirosh I. Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma. Nat Genet. 2023;55:640\u201350.","journal-title":"Nat Genet"},{"key":"8082_CR19","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671\u20135.","journal-title":"Nat Methods"},{"key":"8082_CR20","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, Lee MJ, Wilk AJ, Darby C, Zager M, Hoffman P, Stoeckius M, Papalexi E, Mimitou EP, Jain J, Srivastava A, Stuart T, Fleming LM, Yeung B, Rogers AJ, McElrath JM, Blish CA, Gottardo R, Smibert P, Satija R. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573\u2013e35873529.","journal-title":"Cell"},{"key":"8082_CR21","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289\u201396.","journal-title":"Nat Methods"},{"key":"8082_CR22","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1038\/s41592-023-01933-9","volume":"20","author":"IN Grabski","year":"2023","unstructured":"Grabski IN, Street K, Irizarry RA. Significance analysis for clustering with single-cell RNA-sequencing data. Nat Methods. 2023;20:1196\u2013202.","journal-title":"Nat Methods"},{"key":"8082_CR23","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suv\u00e0 ML, Regev A, Bernstein BE. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396\u2013401.","journal-title":"Science"},{"key":"8082_CR24","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/s41422-019-0195-y","volume":"29","author":"J Peng","year":"2019","unstructured":"Peng J, Sun BF, Chen CY, Zhou JY, Chen YS, Chen H, Liu L, Huang D, Jiang J, Cui GS, Yang Y, Wang W, Guo D, Dai M, Guo J, Zhang T, Liao Q, Liu Y, Zhao YL, Han DL, Zhao Y, Yang YG, Wu W. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019;29:725\u201338.","journal-title":"Cell Res"},{"key":"8082_CR25","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/s12864-021-07739-3","volume":"22","author":"S Kurtenbach","year":"2021","unstructured":"Kurtenbach S, Cruz AM, Rodriguez DA, Durante MA, Harbour JW. Uphyloplot2: visualizing phylogenetic trees from single-cell RNA-seq data. BMC Genomics. 2021;22:419.","journal-title":"BMC Genomics"},{"key":"8082_CR26","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1093\/bioinformatics\/btw325","volume":"32","author":"ZL Skidmore","year":"2016","unstructured":"Skidmore ZL, Wagner AH, Lesurf R, Campbell KM, Kunisaki J, Griffith OL, Griffith M. GenVisR: Genomic Visualizations in R. Bioinformatics. 2016;32:3012\u20134.","journal-title":"Bioinformatics"},{"key":"8082_CR27","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13059-019-1663-x","volume":"20","author":"FA Wolf","year":"2019","unstructured":"Wolf FA, Hamey FK, Plass M, Solana J, Dahlin JS, G\u00f6ttgens B, Rajewsky N, Simon L, Theis FJ. PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells. Genome Biol. 2019;20:59.","journal-title":"Genome Biol"},{"key":"8082_CR28","doi-asserted-by":"publisher","first-page":"7739","DOI":"10.1038\/s41467-023-43120-6","volume":"14","author":"D Pham","year":"2023","unstructured":"Pham D, Tan X, Balderson B, Xu J, Grice LF, Yoon S, Willis EF, Tran M, Lam PY, Raghubar A, Kalita-de Croft P, Lakhani S, Vukovic J, Ruitenberg MJ, Nguyen QH. Robust mapping of spatiotemporal trajectories and cell-cell interactions in healthy and diseased tissues. Nat Commun. 2023;14:7739.","journal-title":"Nat Commun"},{"key":"8082_CR29","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","volume":"17","author":"E Becht","year":"2016","unstructured":"Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Saut\u00e8s-Fridman C, Fridman WH, de Reyni\u00e8s A. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17:218.","journal-title":"Genome Biol"},{"key":"8082_CR30","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.immuni.2022.02.001","volume":"55","author":"M Meylan","year":"2022","unstructured":"Meylan M, Petitprez F, Becht E, Bougo\u00fcin A, Pupier G, Calvez A, Giglioli I, Verkarre V, Lacroix G, Verneau J, Sun CM, Laurent-Puig P, Vano YA, Ela\u00efdi R, M\u00e9jean A, Sanchez-Salas R, Barret E, Cathelineau X, Oudard S, Reynaud CA, de Reyni\u00e8s A, Saut\u00e8s-Fridman C, Fridman WH. Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer. Immunity. 2022;55:527\u2013e541525.","journal-title":"Immunity"},{"key":"8082_CR31","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41587-021-00830-w","volume":"40","author":"DM Cable","year":"2022","unstructured":"Cable DM, Murray E, Zou LS, Goeva A, Macosko EZ, Chen F, Irizarry RA. Robust decomposition of cell type mixtures in spatial transcriptomics. Nat Biotechnol. 2022;40:517\u201326.","journal-title":"Nat Biotechnol"},{"key":"8082_CR32","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1186\/s12859-018-2435-4","volume":"19","author":"M Foroutan","year":"2018","unstructured":"Foroutan M, Bhuva DD, Lyu R, Horan K, Cursons J, Davis MJ. Single sample scoring of molecular phenotypes. BMC Bioinformatics. 2018;19:404.","journal-title":"BMC Bioinformatics"},{"key":"8082_CR33","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nature14129","volume":"517","author":"CGA Network","year":"2015","unstructured":"Network CGA. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576\u201382.","journal-title":"Nature"},{"key":"8082_CR34","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1007\/s00405-020-06214-1","volume":"278","author":"K Metzger","year":"2021","unstructured":"Metzger K, Moratin J, Freier K, Hoffmann J, Zaoui K, Plath M, St\u00f6gbauer F, Freudlsperger C, Hess J, Horn D. A six-gene expression signature related to angiolymphatic invasion is associated with poor survival in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2021;278:1199\u2013207.","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"8082_CR35","doi-asserted-by":"publisher","first-page":"1100417","DOI":"10.3389\/fimmu.2022.1100417","volume":"13","author":"Z Nan","year":"2022","unstructured":"Nan Z, Dou Y, Chen A, Wang K, Sun J, Meng Z, Neckenig M, Ai D, Liu S, Dong Z, Ma C, Cheng Y, Qu X. Identification and validation of a prognostic signature of autophagy, apoptosis and pyroptosis-related genes for head and neck squamous cell carcinoma: to imply therapeutic choices of HPV negative patients. Front Immunol. 2022;13:1100417.","journal-title":"Front Immunol"},{"key":"8082_CR36","doi-asserted-by":"crossref","unstructured":"Novotn\u00fd J, Band\u00farov\u00e1 V, Strnad H, Chovanec M, Hradilov\u00e1 M, \u0160\u00e1chov\u00e1 J, \u0160teffl M, Gru\u0161anovi\u0107 J, Kodet R, Pa\u010des V, Lacina L, Smetana K Jr., Plz\u00e1k J, Kol\u00e1\u0159 M, Vomastek T. Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas and Paired Normal Mucosae Reveals Cyclin D1 Deregulation and Compensatory Effect of Cyclin D2. Cancers (Basel). 2020;12.","DOI":"10.3390\/cancers12040792"},{"key":"8082_CR37","doi-asserted-by":"publisher","first-page":"e56823","DOI":"10.1371\/journal.pone.0056823","volume":"8","author":"V Walter","year":"2013","unstructured":"Walter V, Yin X, Wilkerson MD, Cabanski CR, Zhao N, Du Y, Ang MK, Hayward MC, Salazar AH, Hoadley KA, Fritchie K, Sailey CJ, Weissler MC, Shockley WW, Zanation AM, Hackman T, Thorne LB, Funkhouser WD, Muldrew KL, Olshan AF, Randell SH, Wright FA, Shores CG, Hayes DN. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS ONE. 2013;8:e56823.","journal-title":"PLoS ONE"},{"key":"8082_CR38","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1002\/ijc.29649","volume":"137","author":"G Wichmann","year":"2015","unstructured":"Wichmann G, Rosolowski M, Krohn K, Kreuz M, Boehm A, Reiche A, Scharrer U, Halama D, Bertolini J, Bauer U, Holzinger D, Pawlita M, Hess J, Engel C, Hasenclever D, Scholz M, Ahnert P, Kirsten H, Hemprich A, Wittekind C, Herbarth O, Horn F, Dietz A, Loeffler M. The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer. Int J Cancer. 2015;137:2846\u201357.","journal-title":"Int J Cancer"},{"key":"8082_CR39","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1001\/jamaoncol.2016.3067","volume":"3","author":"G D\u2019Souza","year":"2017","unstructured":"D\u2019Souza G, Westra WH, Wang SJ, van Zante A, Wentz A, Kluz N, Rettig E, Ryan WR, Ha PK, Kang H, Bishop J, Quon H, Kiess AP, Richmon JD, Eisele DW, Fakhry C. Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method. JAMA Oncol. 2017;3:169\u201377.","journal-title":"JAMA Oncol"},{"key":"8082_CR40","doi-asserted-by":"publisher","first-page":"e29386","DOI":"10.1002\/jmv.29386","volume":"96","author":"H Lee","year":"2024","unstructured":"Lee H, Park S, Yun JH, Seo C, Ahn JM, Cha HY, Shin YS, Park HR, Lee D, Roh J, Heo HJ, Baek SE, Kim EK, Lee HS, Kim CH, Kim YH, Jang JY. Deciphering head and neck cancer microenvironment: Single-cell and spatial transcriptomics reveals human papillomavirus-associated differences. J Med Virol. 2024;96:e29386.","journal-title":"J Med Virol"},{"key":"8082_CR41","doi-asserted-by":"publisher","first-page":"103961","DOI":"10.1016\/j.esmoop.2024.103961","volume":"9","author":"MH Hong","year":"2024","unstructured":"Hong MH, Park S, Vo T, Cho J, Jung HA, Lee SH, Kim SH, Zhou H, Chirovsky D, Koh YW, Yoon SO, Webber AL, Gumuscu B, Cho BC, Ahn MJ. Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma. ESMO Open. 2024;9:103961.","journal-title":"ESMO Open"},{"key":"8082_CR42","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12943-023-01761-7","volume":"22","author":"R Ruan","year":"2023","unstructured":"Ruan R, Li L, Li X, Huang C, Zhang Z, Zhong H, Zeng S, Shi Q, Xia Y, Zeng Q, Wen Q, Chen J, Dai X, Xiong J, Xiang X, Lei W, Deng J. Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF\/FGFR signaling in tumor microenvironment. Mol Cancer. 2023;22:60.","journal-title":"Mol Cancer"},{"key":"8082_CR43","doi-asserted-by":"publisher","first-page":"200268","DOI":"10.1016\/j.tvr.2023.200268","volume":"16","author":"J Doorbar","year":"2023","unstructured":"Doorbar J. The human Papillomavirus twilight zone - Latency, immune control and subclinical infection. Tumour Virus Res. 2023;16:200268.","journal-title":"Tumour Virus Res"},{"key":"8082_CR44","doi-asserted-by":"crossref","unstructured":"Porter VL, Marra MA. The Drivers, Mechanisms, and Consequences of Genome Instability in HPV-Driven Cancers. Cancers (Basel). 2022;14.","DOI":"10.3390\/cancers14194623"},{"key":"8082_CR45","doi-asserted-by":"publisher","first-page":"E990","DOI":"10.1073\/pnas.1615758114","volume":"114","author":"K Hoppe-Seyler","year":"2017","unstructured":"Hoppe-Seyler K, Bossler F, Lohrey C, Bulkescher J, R\u00f6sl F, Jansen L, Mayer A, Vaupel P, D\u00fcrst M, Hoppe-Seyler F. Induction of dormancy in hypoxic human papillomavirus-positive cancer cells. Proc Natl Acad Sci U S A. 2017;114:E990\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8082_CR46","doi-asserted-by":"crossref","unstructured":"Bossler F, Kuhn BJ, G\u00fcnther T, Kraemer SJ, Khalkar P, Adrian S, Lohrey C, Holzer A, Shimobayashi M, D\u00fcrst M, Mayer A, R\u00f6sl F, Grundhoff A, Krijgsveld J, Hoppe-Seyler K, Hoppe-Seyler F. Repression of Human Papillomavirus Oncogene Expression under Hypoxia Is Mediated by PI3K\/mTORC2\/AKT Signaling. mBio. 2019;10.","DOI":"10.1128\/mBio.02323-18"},{"key":"8082_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcancer.2023.10.005","volume":"98","author":"R Verdikt","year":"2024","unstructured":"Verdikt R, Thienpont B. Epigenetic remodelling under hypoxia. Semin Cancer Biol. 2024;98:1\u201310.","journal-title":"Semin Cancer Biol"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08082-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08082-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08082-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T01:01:55Z","timestamp":1779066115000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08082-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8082"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08082-5","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"18 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board of the Asan Medical Center (IRB no. 2021\u2009\u2212\u20091235).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"681"}}