{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:59:53Z","timestamp":1782950393076,"version":"3.54.5"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Hamburg-Eppendorf (UKE)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Head and neck squamous cell carcinoma (HNSCC) negative for Human Papillomavirus (HPV) has remained a difficult to treat entity, whereas tumors positive for HPV are characterized by radiosensitivity and favorable patient outcome. On the cellular level, radiosensitivity is largely governed by the tumor cells` ability to repair radiation-induced DNA double-strand breaks (DSBs), but no biomarker is established that could guide clinical decision making. Therefore, we tested the impact of the expression levels of ATM, the central kinase of the DNA damage response as well as DNA-PKcs and Ku80, two major factors in the main DSB repair pathway non-homologous end joining (NHEJ).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A tissue microarray of a single center HNSCC cohort was stained for ATM, DNA-PKcs and Ku80 and the expression scored based on staining intensity and the percentages of tumor cells stained. Scores were correlated with clinicopathological parameters and survival.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Samples from 427 HNSCC patients yielded interpretable stainings and were scored following an established algorithm. The majority of tumors showed strong expression of both NHEJ factors, whereas the expression of ATM varied more. The expression scores of ATM and DNA-PKcs were not associated with patient survival. For HPV-negative HNSCC, the minority of tumors without strong Ku80 expression trended towards superior survival when treatment included radiotherapy. Focusing stronger on staining intensity to define the subgroup with lowest and therefore potentially insufficient expression levels in the HPV-negative subgroup, we observed significantly better overall survival for patients treated with radiotherapy but not with surgery alone.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our data suggest that HPV-negative HNSCC with particularly low Ku80 expression represent a highly radiosensitive subpopulation. Confirmation in independent cohorts is required.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13014-024-02541-3","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:28:07Z","timestamp":1730294887000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tissue microarray analyses of the essential DNA repair factors ATM, DNA-PKcs and Ku80 in head and neck squamous cell carcinoma"],"prefix":"10.1186","volume":"19","author":[{"given":"Henrike Barbara","family":"Zech","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"von Bargen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Oetting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"M\u00f6ckelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"M\u00f6ller-Koop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Witt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Struve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Betz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Rothkamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"M\u00fcnscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till Sebastian","family":"Clauditz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Rieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"issue":"1","key":"2541_CR1","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(1):24\u201335.","journal-title":"N Engl J Med"},{"issue":"12","key":"2541_CR2","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1200\/JCO.2008.20.2853","volume":"27","author":"P Lassen","year":"2009","unstructured":"Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992\u20138.","journal-title":"J Clin Oncol"},{"issue":"6","key":"2541_CR3","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","volume":"66","author":"AN Blackford","year":"2017","unstructured":"Blackford AN, Jackson SP, ATM, ATR DNA-PK. The trinity at the heart of the DNA damage response. Mol Cell. 2017;66(6):801\u201317.","journal-title":"Mol Cell"},{"issue":"2","key":"2541_CR4","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1158\/0008-5472.CAN-03-2384","volume":"64","author":"M Kuhne","year":"2004","unstructured":"Kuhne M, Riballo E, Rief N, Rothkamm K, Jeggo PA, Lobrich M. A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res. 2004;64(2):500\u20138.","journal-title":"Cancer Res"},{"issue":"1","key":"2541_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","volume":"11","author":"C Rothblum-Oviatt","year":"2016","unstructured":"Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016;11(1):159.","journal-title":"Orphanet J Rare Dis"},{"issue":"29","key":"2541_CR6","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1200\/JCO.2015.62.1086","volume":"33","author":"DN Hayes","year":"2015","unstructured":"Hayes DN, Van Waes C, Seiwert TY. Genetic Landscape of Human Papillomavirus-Associated Head and Neck Cancer and comparison to Tobacco-related tumors. J Clin Oncol. 2015;33(29):3227\u201334.","journal-title":"J Clin Oncol"},{"issue":"8","key":"2541_CR7","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.oraloncology.2012.02.014","volume":"48","author":"AM Lim","year":"2012","unstructured":"Lim AM, Young RJ, Collins M, Fox SB, McArthur GA, Corry J, et al. Correlation of Ataxia-Telangiectasia-Mutated (ATM) gene loss with outcome in head and neck squamous cell carcinoma. Oral Oncol. 2012;48(8):698\u2013702.","journal-title":"Oral Oncol"},{"issue":"8","key":"2541_CR8","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1002\/gcc.20462","volume":"46","author":"RA Parikh","year":"2007","unstructured":"Parikh RA, White JS, Huang X, Schoppy DW, Baysal BE, Baskaran R, et al. Loss of distal 11q is associated with DNA repair deficiency and reduced sensitivity to ionizing radiation in head and neck squamous cell carcinoma. Genes Chromosomes Cancer. 2007;46(8):761\u201375.","journal-title":"Genes Chromosomes Cancer"},{"issue":"2","key":"2541_CR9","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/gcc.22125","volume":"53","author":"M Sankunny","year":"2014","unstructured":"Sankunny M, Parikh RA, Lewis DW, Gooding WE, Saunders WS, Gollin SM. Targeted inhibition of ATR or CHEK1 reverses radioresistance in oral squamous cell carcinoma cells with distal chromosome arm 11q loss. Genes Chromosomes Cancer. 2014;53(2):129\u201343.","journal-title":"Genes Chromosomes Cancer"},{"issue":"8","key":"2541_CR10","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nrm.2017.48","volume":"18","author":"HHY Chang","year":"2017","unstructured":"Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol. 2017;18(8):495\u2013506.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1035","key":"2541_CR11","doi-asserted-by":"publisher","first-page":"20130685","DOI":"10.1259\/bjr.20130685","volume":"87","author":"A Kakarougkas","year":"2014","unstructured":"Kakarougkas A, Jeggo PA. DNA DSB repair pathway choice: an orchestrated handover mechanism. Br J Radiol. 2014;87(1035):20130685.","journal-title":"Br J Radiol"},{"issue":"3","key":"2541_CR12","doi-asserted-by":"publisher","first-page":"288","DOI":"10.2307\/3578948","volume":"144","author":"MJ Allalunis-Turner","year":"1995","unstructured":"Allalunis-Turner MJ, Zia PK, Barron GM, Mirzayans R, Day RS. 3rd. Radiation-induced DNA damage and repair in cells of a radiosensitive human malignant glioma cell line. Radiat Res. 1995;144(3):288\u201393.","journal-title":"Radiat Res"},{"issue":"23","key":"2541_CR13","doi-asserted-by":"publisher","first-page":"4778","DOI":"10.1093\/nar\/28.23.4778","volume":"28","author":"E Marangoni","year":"2000","unstructured":"Marangoni E, Foray N, O\u2019Driscoll M, Douc-Rasy S, Bernier J, Bourhis J, et al. A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells. Nucleic Acids Res. 2000;28(23):4778\u201382.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"2541_CR14","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1128\/MCB.17.3.1264","volume":"17","author":"BK Singleton","year":"1997","unstructured":"Singleton BK, Priestley A, Steingrimsdottir H, Gell D, Blunt T, Jackson SP, et al. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol. 1997;17(3):1264\u201373.","journal-title":"Mol Cell Biol"},{"issue":"5","key":"2541_CR15","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1016\/j.ijrobp.2012.02.014","volume":"84","author":"P Bouchaert","year":"2012","unstructured":"Bouchaert P, Guerif S, Debiais C, Irani J, Fromont G. DNA-PKcs expression predicts response to radiotherapy in prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1179\u201385.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"18","key":"2541_CR16","doi-asserted-by":"publisher","first-page":"7017","DOI":"10.1158\/0008-5472.CAN-10-1202","volume":"70","author":"A Choudhury","year":"2010","unstructured":"Choudhury A, Nelson LD, Teo MT, Chilka S, Bhattarai S, Johnston CF, et al. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010;70(18):7017\u201326.","journal-title":"Cancer Res"},{"issue":"4","key":"2541_CR17","doi-asserted-by":"publisher","first-page":"e80","DOI":"10.1097\/01.COC.0000077938.48974.59","volume":"26","author":"Y Harima","year":"2003","unstructured":"Harima Y, Sawada S, Miyazaki Y, Kin K, Ishihara H, Imamura M, et al. Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival. Am J Clin Oncol. 2003;26(4):e80\u20135.","journal-title":"Am J Clin Oncol"},{"issue":"1","key":"2541_CR18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00066-016-1023-7","volume":"193","author":"T Hasegawa","year":"2017","unstructured":"Hasegawa T, Someya M, Hori M, Matsumoto Y, Nakata K, Nojima M, et al. Expression of Ku70 predicts results of radiotherapy in prostate cancer. Strahlenther Onkol. 2017;193(1):29\u201337.","journal-title":"Strahlenther Onkol"},{"issue":"9","key":"2541_CR19","doi-asserted-by":"publisher","first-page":"e74161","DOI":"10.1371\/journal.pone.0074161","volume":"8","author":"S Hu","year":"2013","unstructured":"Hu S, Qu Y, Xu X, Xu Q, Geng J, Xu J. Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array. PLoS ONE. 2013;8(9):e74161.","journal-title":"PLoS ONE"},{"issue":"3","key":"2541_CR20","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.ygyno.2004.08.005","volume":"95","author":"U Saygili","year":"2004","unstructured":"Saygili U, Gorkay IB, Koyuncuoglu M, Gol M, Uslu T, Erten O. The relationship between expression of Ku70 and survival in irradiated patients with endometrial carcinoma. Gynecol Oncol. 2004;95(3):518\u201322.","journal-title":"Gynecol Oncol"},{"issue":"6","key":"2541_CR21","first-page":"1547","volume":"37","author":"K Soderlund Leifler","year":"2010","unstructured":"Soderlund Leifler K, Queseth S, Fornander T, Askmalm MS. Low expression of Ku70\/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer. Int J Oncol. 2010;37(6):1547\u201354.","journal-title":"Int J Oncol"},{"issue":"12","key":"2541_CR22","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1054\/bjoc.2000.1510","volume":"83","author":"CR Wilson","year":"2000","unstructured":"Wilson CR, Davidson SE, Margison GP, Jackson SP, Hendry JH, West CM. Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer. 2000;83(12):1702\u20136.","journal-title":"Br J Cancer"},{"issue":"4","key":"2541_CR23","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/hed.10199","volume":"25","author":"S Friesland","year":"2003","unstructured":"Friesland S, Kanter-Lewensohn L, Tell R, Munck-Wikland E, Lewensohn R, Nilsson A. Expression of Ku86 confers favorable outcome of tonsillar carcinoma treated with radiotherapy. Head Neck. 2003;25(4):313\u201321.","journal-title":"Head Neck"},{"issue":"5","key":"2541_CR24","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1002\/ijc.23635","volume":"123","author":"MA Pavon","year":"2008","unstructured":"Pavon MA, Parreno M, Leon X, Sancho FJ, Cespedes MV, Casanova I, et al. Ku70 predicts response and primary tumor recurrence after therapy in locally advanced head and neck cancer. Int J Cancer. 2008;123(5):1068\u201379.","journal-title":"Int J Cancer"},{"issue":"5","key":"2541_CR25","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/j.ijrobp.2004.12.049","volume":"62","author":"SW Lee","year":"2005","unstructured":"Lee SW, Cho KJ, Park JH, Kim SY, Nam SY, Lee BJ, et al. Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2005;62(5):1451\u20137.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"4","key":"2541_CR26","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.4103\/jcrt.JCRT_582_19","volume":"17","author":"JS Joshi","year":"2021","unstructured":"Joshi JS, Vora HH, Ghosh NR, Tankshali RN, Jetly DH, Trivedi TI. Nonhomologous end joining repair pathway molecules as predictive biomarkers for patients with oral squamous cell carcinoma. J Cancer Res Ther. 2021;17(4):1031\u20138.","journal-title":"J Cancer Res Ther"},{"issue":"7","key":"2541_CR27","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1158\/1078-0432.CCR-10-2641","volume":"17","author":"BJ Moeller","year":"2011","unstructured":"Moeller BJ, Yordy JS, Williams MD, Giri U, Raju U, Molkentine DP, et al. DNA repair biomarker profiling of head and neck cancer: Ku80 expression predicts locoregional failure and death following radiotherapy. Clin Cancer Res. 2011;17(7):2035\u201343.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"2541_CR28","first-page":"803","volume":"59","author":"L Bubendorf","year":"1999","unstructured":"Bubendorf L, Kononen J, Koivisto P, Schraml P, Moch H, Gasser TC, et al. Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res. 1999;59(4):803\u20136.","journal-title":"Cancer Res"},{"key":"2541_CR29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-1-59745-545-9_4","volume":"576","author":"AM Dancau","year":"2010","unstructured":"Dancau AM, Simon R, Mirlacher M, Sauter G. Tissue microarrays. Methods Mol Biol. 2010;576:49\u201360.","journal-title":"Methods Mol Biol"},{"key":"2541_CR30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/978-1-60761-806-5_12","volume":"664","author":"R Simon","year":"2010","unstructured":"Simon R, Mirlacher M, Sauter G. Immunohistochemical analysis of tissue microarrays. Methods Mol Biol. 2010;664:113\u201326.","journal-title":"Methods Mol Biol"},{"key":"2541_CR31","doi-asserted-by":"publisher","first-page":"151793","DOI":"10.1016\/j.anndiagpath.2021.151793","volume":"54","author":"S Steurer","year":"2021","unstructured":"Steurer S, Schneider J, Buscheck F, Luebke AM, Kluth M, Hube-Magg C, et al. Immunohistochemically detectable thyroglobulin expression in extrathyroidal cancer is 100% specific for thyroidal tumor origin. Ann Diagn Pathol. 2021;54:151793.","journal-title":"Ann Diagn Pathol"},{"issue":"2","key":"2541_CR32","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nmeth.3252","volume":"12","author":"W Huber","year":"2015","unstructured":"Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115\u201321.","journal-title":"Nat Methods"},{"key":"2541_CR33","unstructured":"Kassambara A, Kosinski M, survminer. Drawing Survival Curves using \u2018ggplot2\u2019. R package version 0.4.3. https:\/\/CRANR-projectorg\/package=survminer. 2018."},{"key":"2541_CR34","doi-asserted-by":"crossref","unstructured":"Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. Springer, New York ISBN 0-387-98784-3. 2000.","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"2541_CR35","unstructured":"Wei T, Simko V. R package corrplot: visualization of a correlation matrix (Version. 84). https:\/\/githubcom\/taiyun\/corrplot. 2017."},{"issue":"12","key":"2541_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v021.i12","volume":"21","author":"H Wickham","year":"2007","unstructured":"Wickham H. Reshaping data with the reshape Package. J Stat Softw. 2007;21(12):1\u201320. http:\/\/www.jstatsoft.org\/v21\/i12\/. .","journal-title":"J Stat Softw"},{"issue":"6","key":"2541_CR37","doi-asserted-by":"publisher","first-page":"djv403","DOI":"10.1093\/jnci\/djv403","volume":"108","author":"X Castellsague","year":"2016","unstructured":"Castellsague X, Alemany L, Quer M, Halec G, Quiros B, Tous S, et al. HPV involvement in Head and Neck cancers: Comprehensive Assessment of biomarkers in 3680 patients. J Natl Cancer Inst. 2016;108(6):djv403.","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"2541_CR38","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1002\/ijc.33514","volume":"149","author":"IH Nauta","year":"2021","unstructured":"Nauta IH, Heideman DAM, van der Brink A, Bloemena E, Koljenovic S, et al. The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma. Int J Cancer. 2021;149(2):420\u201330.","journal-title":"Int J Cancer"},{"key":"2541_CR39","doi-asserted-by":"publisher","first-page":"101925","DOI":"10.1016\/j.canep.2021.101925","volume":"72","author":"C Simoens","year":"2021","unstructured":"Simoens C, Gorbaslieva I, Gheit T, Holzinger D, Lucas E, Ridder R, et al. HPV DNA genotyping, HPV E6*I mRNA detection, and p16(INK4a)\/Ki-67 staining in Belgian head and neck cancer patient specimens, collected within the HPV-AHEAD study. Cancer Epidemiol. 2021;72:101925.","journal-title":"Cancer Epidemiol"},{"key":"2541_CR40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.oraloncology.2016.08.009","volume":"61","author":"M Taberna","year":"2016","unstructured":"Taberna M, Resteghini C, Swanson B, Pickard RK, Jiang B, Xiao W, et al. Low etiologic fraction for human papillomavirus in larynx squamous cell carcinoma. Oral Oncol. 2016;61:55\u201361.","journal-title":"Oral Oncol"},{"key":"2541_CR41","doi-asserted-by":"crossref","unstructured":"Tagliabue M, Mena M, Maffini F, Gheit T, Quiros Blasco B, Holzinger D et al. Role of human papillomavirus infection in Head and Neck Cancer in Italy: the HPV-AHEAD study. Cancers (Basel). 2020;12(12).","DOI":"10.3390\/cancers12123567"},{"issue":"11","key":"2541_CR42","doi-asserted-by":"publisher","first-page":"3837","DOI":"10.1007\/s00405-017-4718-1","volume":"274","author":"C Wittekindt","year":"2017","unstructured":"Wittekindt C, Wuerdemann N, Gattenlohner S, Brobeil A, Wierzbicka M, Wagner S, et al. The role of high-risk human papillomavirus infections in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2017;274(11):3837\u201342.","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"2541_CR43","doi-asserted-by":"publisher","first-page":"765968","DOI":"10.3389\/fonc.2022.765968","volume":"12","author":"S Kocher","year":"2022","unstructured":"Kocher S, Zech HB, Krug L, Gatzemeier F, Christiansen S, Meyer F, et al. A lack of effectiveness in the ATM-Orchestrated DNA damage response contributes to the DNA repair defect of HPV-Positive Head and Neck Cancer cells. Front Oncol. 2022;12:765968.","journal-title":"Front Oncol"},{"issue":"23","key":"2541_CR44","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1158\/1078-0432.CCR-18-1346","volume":"24","author":"Q Liu","year":"2018","unstructured":"Liu Q, Ma L, Jones T, Palomero L, Pujana MA, Martinez-Ruiz H, et al. Subjugation of TGFbeta Signaling by Human Papilloma Virus in Head and Neck squamous cell carcinoma shifts DNA repair from homologous recombination to alternative end joining. Clin Cancer Res. 2018;24(23):6001\u201314.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"2541_CR45","doi-asserted-by":"publisher","first-page":"10312","DOI":"10.18632\/oncotarget.14400","volume":"8","author":"J Ma","year":"2017","unstructured":"Ma J, Setton J, Morris L, Albornoz PB, Barker C, Lok BH, et al. Genomic analysis of exceptional responders to radiotherapy reveals somatic mutations in ATM. Oncotarget. 2017;8(6):10312\u201323.","journal-title":"Oncotarget"},{"issue":"49","key":"2541_CR46","doi-asserted-by":"publisher","first-page":"18597","DOI":"10.1073\/pnas.0609061103","volume":"103","author":"PO Mari","year":"2006","unstructured":"Mari PO, Florea BI, Persengiev SP, Verkaik NS, Bruggenwirth HT, Modesti M, et al. Dynamic assembly of end-joining complexes requires interaction between Ku70\/80 and XRCC4. Proc Natl Acad Sci U S A. 2006;103(49):18597\u2013602.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"2541_CR47","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.dnarep.2011.12.007","volume":"11","author":"Z Shao","year":"2012","unstructured":"Shao Z, Davis AJ, Fattah KR, So S, Sun J, Lee KJ, et al. Persistently bound Ku at DNA ends attenuates DNA end resection and homologous recombination. DNA Repair (Amst). 2012;11(3):310\u20136.","journal-title":"DNA Repair (Amst)"},{"issue":"6","key":"2541_CR48","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/ncb1591","volume":"9","author":"E Soutoglou","year":"2007","unstructured":"Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T, et al. Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol. 2007;9(6):675\u201382.","journal-title":"Nat Cell Biol"},{"issue":"12","key":"2541_CR49","doi-asserted-by":"publisher","first-page":"4088","DOI":"10.1093\/nar\/gkn347","volume":"36","author":"WY Mansour","year":"2008","unstructured":"Mansour WY, Schumacher S, Rosskopf R, Rhein T, Schmidt-Petersen F, Gatzemeier F, et al. Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res. 2008;36(12):4088\u201398.","journal-title":"Nucleic Acids Res"},{"issue":"21","key":"2541_CR50","doi-asserted-by":"publisher","first-page":"6170","DOI":"10.1093\/nar\/gkl840","volume":"34","author":"M Wang","year":"2006","unstructured":"Wang M, Wu W, Wu W, Rosidi B, Zhang L, Wang H, et al. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006;34(21):6170\u201382.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2541_CR51","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41467-022-28158-2","volume":"13","author":"Y Chen","year":"2022","unstructured":"Chen Y, Zhao Y, Yang X, Ren X, Huang S, Gong S, et al. USP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma. Nat Commun. 2022;13(1):501.","journal-title":"Nat Commun"},{"key":"2541_CR52","doi-asserted-by":"publisher","first-page":"176647","DOI":"10.1016\/j.ejphar.2024.176647","volume":"975","author":"X Chen","year":"2024","unstructured":"Chen X, Chen C, Luo C, Liu J, Lin Z. Discovery of UMI-77 as a novel Ku70\/80 inhibitor sensitizing cancer cells to DNA damaging agents in vitro and in vivo. Eur J Pharmacol. 2024;975:176647.","journal-title":"Eur J Pharmacol"},{"issue":"5","key":"2541_CR53","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1002\/ijc.30516","volume":"140","author":"ES Prigge","year":"2017","unstructured":"Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M. Diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Int J Cancer. 2017;140(5):1186\u201398.","journal-title":"Int J Cancer"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-024-02541-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13014-024-02541-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-024-02541-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:30:59Z","timestamp":1730295059000},"score":1,"resource":{"primary":{"URL":"https:\/\/ro-journal.biomedcentral.com\/articles\/10.1186\/s13014-024-02541-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2541"],"URL":"https:\/\/doi.org\/10.1186\/s13014-024-02541-3","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"assertion":[{"value":"6 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Patient consent was waived because the use of archived remnants of diagnostic tissues and their analysis for research purposes as well as patient data analysis have been approved by local laws (HmbKHG,\u00a7\u00a012,1) and by the local ethics committee (Ethics commission Hamburg, WF-049\/09). The whole study has been carried out in compliance with the Helsinki Declaration.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"150"}}