{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:40:33Z","timestamp":1790113233162,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010358","name":"KV Fonden","doi-asserted-by":"publisher","award":["6030\/67"],"award-info":[{"award-number":["6030\/67"]}],"id":[{"id":"10.13039\/501100010358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023490","name":"IMK Almene Fond","doi-asserted-by":"publisher","award":["30\u2010206\u2010365"],"award-info":[{"award-number":["30\u2010206\u2010365"]}],"id":[{"id":"10.13039\/501100023490","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006576","name":"Civilingeni\u00f8r Frode V. Nyegaard og Hustrus Fond","doi-asserted-by":"publisher","award":["12062018"],"award-info":[{"award-number":["12062018"]}],"id":[{"id":"10.13039\/501100006576","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010347","name":"Fabrikant Einar Willumsens Mindelegat","doi-asserted-by":"publisher","award":["6000073"],"award-info":[{"award-number":["6000073"]}],"id":[{"id":"10.13039\/501100010347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010347","name":"Fabrikant Einar Willumsens Mindelegat","doi-asserted-by":"publisher","award":["500028"],"award-info":[{"award-number":["500028"]}],"id":[{"id":"10.13039\/501100010347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009906","name":"Grosserer A.V. Lykfeldt og Hustrus Legat","doi-asserted-by":"publisher","award":["27022021"],"award-info":[{"award-number":["27022021"]}],"id":[{"id":"10.13039\/501100009906","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008262","name":"Harboefonden","doi-asserted-by":"publisher","award":["19181"],"award-info":[{"award-number":["19181"]}],"id":[{"id":"10.13039\/501100008262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008141","name":"Inge og J\u00f8rgen Larsens Mindelegat","doi-asserted-by":"publisher","award":["105 37\u201005"],"award-info":[{"award-number":["105 37\u201005"]}],"id":[{"id":"10.13039\/501100008141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Circulating cell\u2010free human papillomavirus (ccfHPV) DNA is a promising biomarker for cervical cancer monitoring. This study used next\u2010generation sequencing (NGS) to assess its prognostic and surveillance value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The authors included 141 cervical cancer patients (International Federation of Gynecology and Obstetrics IA1\u2013IVB) grouped by treatment: primary surgery (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a050), primary surgery\u00a0+\u00a0adjuvant oncological (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a022), and primary oncological treatment (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a069). Plasma was collected pretreatment, at early follow\u2010up (first post\u2010treatment sample [FPS]), and during longer follow\u2010up. ccfHPV DNA was detected using an NGS\u2010based assay, enabling high sensitivity without prior knowledge of human papillomavirus (HPV) genotype. Associations between ccfHPV DNA status and recurrence were assessed using Cox proportional hazards models, and predictive accuracy was evaluated via sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pretreatment ccfHPV DNA positivity was detected in 8.0%, 36.4%, and 82.6% of patients across the groups, and ccfHPV DNA positivity was significantly associated with higher recurrence risk (adjusted hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.29\u201318.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.02). At FPS, ccfHPV DNA positivity strongly predicted recurrence (adjusted HR, 19.1; 95% CI, 7.27\u201350.2), with a PPV of 83% and NPV of 90% for recurrence within 50 months. Among patients who developed recurrence, ccfHPV DNA was detectable before clinical evidence of recurrence in 60.9% of cases with a mean lead time of 144 days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ccfHPV DNA detected by NGS is a strong prognostic biomarker for residual disease or recurrence. Its strong performance, already at early follow\u2010up, supports its integration into individualized follow\u2010up strategies. Prospective multicenter studies should validate these findings and guide clinical implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      The study was registered with\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (identifiers: NCT03749720)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70282","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T12:38:31Z","timestamp":1770467911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ultrasensitive next\u2010generation sequencing\u2013based detection of circulating human papillomavirus DNA for cervical cancer recurrence monitoring"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-1288","authenticated-orcid":false,"given":"Sara","family":"B\u00f8nl\u00f8kke","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Obstetrics and Gynecology G\u00f8dstrup Regional Hospital  Herning Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Stougaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boe Sandahl","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Clinical Biochemistry Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Parner","sequence":"additional","affiliation":[{"name":"Department of Public Health, Unit for Biostatistics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte\u2010Bettina","family":"Nyvang","sequence":"additional","affiliation":[{"name":"Department of Oncology Odense University Hospital  Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob Christian","family":"Lindegaard","sequence":"additional","affiliation":[{"name":"Department of Oncology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Blaak\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Odense University Hospital  Odense C Denmark"},{"name":"Department of Clinical Research University of Southern Denmark  Odense M Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Fuglsang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Obstetrics and Gynecology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Steiniche","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13538\/v2\/response1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142170"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096\u20109896(199909)189:1<12::aid\u2010path431>3.0.co;2\u2010f"},{"key":"e_1_2_9_5_1","unstructured":"Dansk Gyn\u00e6kologisk Cancergruppe.Dansk gyn\u00e6kologisk cancer database. Accessed October 24; 2025.https:\/\/dgcg.dk\/index.php\/database"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.09.008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.02.021"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.03.038"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2017.1530"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.12.018"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010025\u201000876\u2010y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/po.18.00152"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2022.07.028"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201023\u20103941"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100154"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.47"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201021\u20100625"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201019\u20102384"},{"key":"e_1_2_9_19_1","article-title":"Clinical validation of human papilloma virus circulating tumor DNA for early detection of residual disease after chemoradiation in cervical cancer","author":"Han K","year":"2023","journal-title":"J Clin Oncol"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010023\u201002233\u2010x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201021\u20100293"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15092590"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12749"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201018\u20100922"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00505"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030652"},{"key":"e_1_2_9_27_1","volume-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans","author":"The International Agency for Research on Cancer","year":"2007"},{"key":"e_1_2_9_28_1","volume-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 90. Human Papillomaviruses","author":"World Health Organization","year":"2007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104568"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjgenmed.2016.4"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw100"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201017\u20101553"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2019.03.005"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191581"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100230"},{"issue":"19","key":"e_1_2_9_36_1","article-title":"Detection of circulating tumor DNA in early and late stage human malignancies","volume":"74","author":"Bettegowda C","year":"2014","journal-title":"Cancer Res"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70282","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.70282","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:32:38Z","timestamp":1780655558000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.70282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,7]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2,15]]}},"alternative-id":["10.1002\/cncr.70282"],"URL":"https:\/\/doi.org\/10.1002\/cncr.70282","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,7]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70282"}}