{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:57:33Z","timestamp":1790632653556,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009844","name":"PA Research Foundation","doi-asserted-by":"publisher","award":["RSS_2021_177"],"award-info":[{"award-number":["RSS_2021_177"]}],"id":[{"id":"10.13039\/100009844","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Gene Ther"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integration of high-dimensional tumor gene expression data with clinicopathological data can increase our understanding of disease diversity, enable retrospective patient stratification, and identify new potential biomarkers and therapeutic targets. Using a systems biology approach, we provide a holistic overview of gene co-expression networks in head and neck squamous cell carcinomas (HNSCC). Weighted gene co-expression network analysis of HNSCC RNA sequencing data from 519 patients from The Cancer Genome Atlas (TCGA) was used to determine correlates of 5-year survival, using regression tree-based optimal threshold calculations. Survival-associated gene sets were transformed to gene set scores that were assessed for correlation with clinicopathological data. We identified 8 gene co-expression modules for HNSCC tumors, each of which contained co-expressed genes associated significantly with 5-year survival. Survival-associated co-expression gene signatures correlated dominantly with tumor HPV and p16 status. Network analysis identified that survival was associated with signaling networks of infection, immunity, epithelial-mesenchymal transition (EMT), hypoxia, glycolysis, focal adhesion, extracellular matrix, MYC signaling, autophagy and transcriptional regulation. EMT-associated gene signatures were expressed dominantly in fibroblasts, and cancer-associated fibroblasts were inversely correlated with immune activity. Interestingly, a high Immune Suppression Score based on expression of 21 genes associated with immune inhibition and including immune checkpoints, cytokines and regulatory T cell factors, was also associated with increased survival probability, and was significantly higher in HPV+\u2009HNSCC. Networks associated with HNSCC survival were further associated with survival in cervical cancer, melanoma and lung cancer. This study defines 5129 genes associated with HNSCC survival, organized into co-expressed networks, their correlation with clinicopathological data, and with gene expression data from other malignant diseases, and provides a source for the discovery of biomarkers and novel therapies for HNSCC.<\/jats:p>","DOI":"10.1038\/s41417-022-00577-9","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T15:03:41Z","timestamp":1672153421000},"page":"629-640","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HPV status represents dominant trait driving delineation of survival-associated gene co-expression networks in head and neck cancer"],"prefix":"10.1038","volume":"30","author":[{"given":"Ahmed M.","family":"Mehdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Turrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euan","family":"Walpole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Porceddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"Frazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4456-9480","authenticated-orcid":false,"given":"Janin","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"577_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394\u2013424.","journal-title":"CA Cancer J Clin"},{"key":"577_CR2","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.rcl.2021.05.005","volume":"59","author":"C Marcus","year":"2021","unstructured":"Marcus C, Sheikhbahaei S, Shivamurthy VKN, Avey G, Subramaniam RM. PET imaging for head and neck cancers. Radio Clin North Am. 2021;59:773\u201388.","journal-title":"Radio Clin North Am"},{"key":"577_CR3","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","volume":"375","author":"RL Ferris","year":"2016","unstructured":"Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856\u201367.","journal-title":"N Engl J Med"},{"key":"577_CR4","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/S0140-6736(19)32591-7","volume":"394","author":"B Burtness","year":"2019","unstructured":"Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915\u201328.","journal-title":"Lancet."},{"key":"577_CR5","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2018.02.052","volume":"173","author":"J Liu","year":"2018","unstructured":"Liu J, Lichtenberg T, Hoadley KA, Poisson LM, Lazar AJ, Cherniack AD, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell. 2018;173:400\u201316.e11","journal-title":"Cell."},{"key":"577_CR6","doi-asserted-by":"publisher","first-page":"622643","DOI":"10.3389\/fmolb.2021.622643","volume":"8","author":"M Budhwani","year":"2021","unstructured":"Budhwani M, Turrell G, Yu M, Frazer IH, Mehdi AM, Chandra J. Immune-inhibitory gene expression is positively correlated with overall immune activity and predicts increased survival probability of cervical and head and neck cancer patients. Front Mol Biosci. 2021;8:622643.","journal-title":"Front Mol Biosci"},{"key":"577_CR7","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","volume":"171","author":"SV Puram","year":"2017","unstructured":"Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171:1611\u201324.e24.","journal-title":"Cell."},{"key":"577_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 2008;9:559.","journal-title":"BMC Bioinforma"},{"key":"577_CR9","doi-asserted-by":"crossref","unstructured":"Langfelder P, Horvath S. Fast R functions for robust correlations and hierarchical clustering. J Stat Softw. 2012;46:i11.","DOI":"10.18637\/jss.v046.i11"},{"key":"577_CR10","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","volume":"53","author":"EL Kaplan","year":"1958","unstructured":"Kaplan EL, Meier P. Nonparametric-estimation from incomplete observations. J Am Stat Assoc. 1958;53:457\u201381.","journal-title":"J Am Stat Assoc"},{"key":"577_CR11","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36:411\u201320.","journal-title":"Nat Biotechnol"},{"key":"577_CR12","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonzalez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14:1083\u20136.","journal-title":"Nat Methods"},{"key":"577_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v032.i06","volume":"32","author":"T Benaglia","year":"2009","unstructured":"Benaglia T, Chauveau D, Hunter DR, Young DS. mixtools: An R Package for Analyzing Mixture Models. J Stat Softw. 2009;32:1\u201329.","journal-title":"J Stat Softw"},{"key":"577_CR14","doi-asserted-by":"publisher","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 Bioinforma. 2018;19:404.","journal-title":"BMC Bioinforma"},{"key":"577_CR15","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/S1470-2045(14)70471-1","volume":"15","author":"C Ndiaye","year":"2014","unstructured":"Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsague X, Laporte L, et al. HPV DNA, E6\/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol. 2014;15:1319\u201331.","journal-title":"Lancet Oncol"},{"key":"577_CR16","doi-asserted-by":"publisher","first-page":"102368","DOI":"10.1016\/j.isci.2021.102368","volume":"24","author":"A Bubie","year":"2021","unstructured":"Bubie A, Zoulim F, Testoni B, Miles B, Posner M, Villanueva A, et al. Landscape of oncoviral genotype and co-infection via human papilloma and hepatitis B viral tumor in situ profiling. iScience. 2021;24:102368.","journal-title":"iScience"},{"key":"577_CR17","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-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24\u201335.","journal-title":"N Engl J Med"},{"key":"577_CR18","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/jnci\/djn011","volume":"100","author":"C Fakhry","year":"2008","unstructured":"Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261\u20139.","journal-title":"J Natl Cancer Inst"},{"key":"577_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-01594-0","volume":"20","author":"C Yang","year":"2020","unstructured":"Yang C, Zhang ZC, Liu TB, Xu Y, Xia BR, Lou G. E2F1\/2\/7\/8 as independent indicators of survival in patients with cervical squamous cell carcinoma. Cancer Cell Int. 2020;20:500.","journal-title":"Cancer Cell Int"},{"key":"577_CR20","doi-asserted-by":"crossref","unstructured":"Scarth JA, Patterson MR, Morgan EL, Macdonald A. The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation. J Gen Virol. 2021;102:001540.","DOI":"10.1099\/jgv.0.001540"},{"key":"577_CR21","doi-asserted-by":"publisher","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","volume":"3","author":"M Cassandri","year":"2017","unstructured":"Cassandri M, Smirnov A, Novelli F, Pitolli C, Agostini M, Malewicz M, et al. Zinc-finger proteins in health and disease. Cell Death Discov. 2017;3:17071.","journal-title":"Cell Death Discov"},{"key":"577_CR22","first-page":"S48","volume":"97(S 01)","author":"C Wittekindt","year":"2018","unstructured":"Wittekindt C, Wagner S, Sharma SJ, Wurdemann N, Knuth J, Reder H, et al. HPV - A different view on Head and Neck Cancer. Laryngorhinootologie. 2018;97(S 01):S48\u2013S113.","journal-title":"Laryngorhinootologie."},{"key":"577_CR23","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1084\/jem.20062512","volume":"204","author":"S Deaglio","year":"2007","unstructured":"Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257\u201365.","journal-title":"J Exp Med"},{"key":"577_CR24","doi-asserted-by":"publisher","first-page":"1744946","DOI":"10.1080\/2162402X.2020.1744946","volume":"9","author":"I Shevchenko","year":"2020","unstructured":"Shevchenko I, Mathes A, Groth C, Karakhanova S, Muller V, Utikal J, et al. Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses. Oncoimmunology. 2020;9:1744946.","journal-title":"Oncoimmunology."},{"key":"577_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14060-x","volume":"11","author":"M Yu","year":"2020","unstructured":"Yu M, Guo G, Huang L, Deng L, Chang CS, Achyut BR, et al. CD73 on cancer-associated fibroblasts enhanced by the A2B-mediated feedforward circuit enforces an immune checkpoint. Nat Commun. 2020;11:515.","journal-title":"Nat Commun"},{"key":"577_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01367-x","volume":"20","author":"M Herrera","year":"2021","unstructured":"Herrera M, Berral-Gonzalez A, Lopez-Cade I, Galindo-Pumarino C, Bueno-Fortes S, Martin-Merino M, et al. Cancer-associated fibroblast-derived gene signatures determine prognosis in colon cancer patients. Mol Cancer. 2021;20:73.","journal-title":"Mol Cancer"},{"key":"577_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01291-6","volume":"20","author":"SK Madden","year":"2021","unstructured":"Madden SK, de Araujo AD, Gerhardt M, Fairlie DP, Mason JM. Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc. Mol Cancer. 2021;20:3.","journal-title":"Mol Cancer"},{"key":"577_CR28","doi-asserted-by":"crossref","unstructured":"Masso-Valles D, Soucek L. Blocking Myc to treat cancer: reflecting on two decades of Omomyc. Cells. 2020;9:883.","DOI":"10.3390\/cells9040883"},{"key":"577_CR29","doi-asserted-by":"crossref","unstructured":"Schulze A, Oshi M, Endo I, Takabe K. MYC targets scores are associated with cancer aggressiveness and poor survival in ER-positive primary and metastatic breast cancer. Int J Mol Sci. 2020;21:8127.","DOI":"10.3390\/ijms21218127"},{"key":"577_CR30","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1002\/lary.27807","volume":"129","author":"E Du","year":"2019","unstructured":"Du E, Mazul AL, Farquhar D, Brennan P, Anantharaman D, Abedi-Ardekani B, et al. Long-term survival in head and neck cancer: impact of site, stage, smoking, and human papillomavirus status. Laryngoscope. 2019;129:2506\u201313.","journal-title":"Laryngoscope."},{"key":"577_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21988-6","volume":"12","author":"S Muralidharan","year":"2022","unstructured":"Muralidharan S, Ali S, Yang L, Badshah J, Zahir SF, Ali RA, et al. Environmental pathways affecting gene expression (E.PAGE) as an R package to predict gene-environment associations. Sci Rep. 2022;12:18710.","journal-title":"Sci Rep."},{"key":"577_CR32","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.oraloncology.2016.04.004","volume":"58","author":"CN Saber","year":"2016","unstructured":"Saber CN, Gronhoj Larsen C, Dalianis T, von Buchwald C. Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: review of the literature. Oral Oncol. 2016;58:8\u201313.","journal-title":"Oral Oncol"},{"key":"577_CR33","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.immuni.2019.11.014","volume":"52","author":"AR Cillo","year":"2020","unstructured":"Cillo AR, Kurten CHL, Tabib T, Qi Z, Onkar S, Wang T, et al. Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity. 2020;52:183\u201399.e9.","journal-title":"Immunity."},{"key":"577_CR34","first-page":"20180047","volume":"92","author":"EL Gottgens","year":"2019","unstructured":"Gottgens EL, Ostheimer C, Span PN, Bussink J, Hammond EM. HPV, hypoxia and radiation response in head and neck cancer. Br J Radiol. 2019;92:20180047.","journal-title":"Br J Radiol"},{"key":"577_CR35","doi-asserted-by":"publisher","first-page":"565306","DOI":"10.3389\/fonc.2020.565306","volume":"10","author":"AM Knops","year":"2020","unstructured":"Knops AM, South A, Rodeck U, Martinez-Outschoorn U, Harshyne LA, Johnson J, et al. Cancer-associated fibroblast density, prognostic characteristics, and recurrence in head and neck squamous cell carcinoma: a meta-analysis. Front Oncol. 2020;10:565306.","journal-title":"Front Oncol"},{"key":"577_CR36","doi-asserted-by":"publisher","first-page":"4887","DOI":"10.1038\/s41388-019-0765-y","volume":"38","author":"L Bu","year":"2019","unstructured":"Bu L, Baba H, Yoshida N, Miyake K, Yasuda T, Uchihara T, et al. Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment. Oncogene. 2019;38:4887\u2013901.","journal-title":"Oncogene."},{"key":"577_CR37","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature03688","volume":"436","author":"DC Radisky","year":"2005","unstructured":"Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005;436:123\u20137.","journal-title":"Nature."},{"key":"577_CR38","doi-asserted-by":"publisher","first-page":"4584","DOI":"10.1158\/1078-0432.CCR-07-5211","volume":"14","author":"E Ostermann","year":"2008","unstructured":"Ostermann E, Garin-Chesa P, Heider KH, Kalat M, Lamche H, Puri C, et al. Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clin Cancer Res. 2008;14:4584\u201392.","journal-title":"Clin Cancer Res"},{"key":"577_CR39","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/nature08822","volume":"463","author":"R Beroukhim","year":"2010","unstructured":"Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463:899\u2013905.","journal-title":"Nature."},{"key":"577_CR40","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1111\/j.1600-0714.2009.00781.x","volume":"38","author":"N Bhattacharya","year":"2009","unstructured":"Bhattacharya N, Roy A, Roy B, Roychoudhury S, Panda CK. MYC gene amplification reveals clinical association with head and neck squamous cell carcinoma in Indian patients. J Oral Pathol Med. 2009;38:759\u201363.","journal-title":"J Oral Pathol Med"},{"key":"577_CR41","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/odi.12254","volume":"21","author":"MK Sannigrahi","year":"2015","unstructured":"Sannigrahi MK, Singh V, Sharma R, Panda NK, Khullar M. Role of autophagy in head and neck cancer and therapeutic resistance. Oral Dis. 2015;21:283\u201391.","journal-title":"Oral Dis"},{"key":"577_CR42","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.yexmp.2010.11.011","volume":"90","author":"N Vigneswaran","year":"2011","unstructured":"Vigneswaran N, Wu J, Song A, Annapragada A, Zacharias W. Hypoxia-induced autophagic response is associated with aggressive phenotype and elevated incidence of metastasis in orthotopic immunocompetent murine models of head and neck squamous cell carcinomas (HNSCC). Exp Mol Pathol. 2011;90:215\u201325.","journal-title":"Exp Mol Pathol"}],"container-title":["Cancer Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41417-022-00577-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41417-022-00577-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41417-022-00577-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T23:05:14Z","timestamp":1681513514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41417-022-00577-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,27]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["577"],"URL":"https:\/\/doi.org\/10.1038\/s41417-022-00577-9","relation":{},"ISSN":["0929-1903","1476-5500"],"issn-type":[{"value":"0929-1903","type":"print"},{"value":"1476-5500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,27]]},"assertion":[{"value":"19 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AMM is employed by QCIF Bioinformatics. IHF receives funding from Jingang Medicine Pty Ltd for clinical trial research for HNSCC.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study only used publicly available non-identifiable data. Data sources are clearly indicated.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}