{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:04:59Z","timestamp":1787738699527,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T00:00:00Z","timestamp":1528329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Candys Foundation and Kraeftfonden"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Otolaryngology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The incidence of human papillomavirus\u2010induced (<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>+) head and neck squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">HNSCC<\/jats:styled-content>), that is, especially oropharyngeal cancers (<jats:styled-content style=\"fixed-case\">OPSCC<\/jats:styled-content>), is increasing, and a significant proportion of patients encounter disease progression. A simple and sensitive test to identify patients with progression is an unmet need.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective of Review<\/jats:title><jats:p>To systematically review the literature and carry out a meta\u2010analysis of studies, investigating circulating <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> as a biomarker for disease progression in patients with <jats:styled-content style=\"fixed-case\">HNSCC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Type of Review<\/jats:title><jats:p>A systematic review and meta\u2010analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Search Strategy<\/jats:title><jats:p>PubMed, <jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content> and the Cochrane Library were systematically searched for articles published in English from January 1980 to November 2017. Search terms used were related to <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>, cancer sites, blood\u2010based biomarkers and terms for specific use settings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evaluation Method<\/jats:title><jats:p>Articles reviewed and selected by authors and data on study design, demographic variables, location, <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> status, number of pre\u2010treatment blood tests, number of post\u2010treatment blood tests, blood <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> status and number of recurrences and length of follow\u2010up were extracted. A meta\u2010analysis of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> as a diagnostic test for recurrence by means of a hierarchical summary receiver operating curve (<jats:styled-content style=\"fixed-case\">HSROC<\/jats:styled-content>) model was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 5 studies (n\u00a0=\u00a0600 subjects) examining circulating <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> in patients with <jats:styled-content style=\"fixed-case\">HNSCC<\/jats:styled-content>. In these 5 studies (n\u00a0=\u00a0411), patients had both pre\u2010 and post\u2010treatment blood samples. The pooled sensitivity, in detecting a recurrence, was estimated to be 54% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 32%\u201074%), while the pooled specificity was 98% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 93%\u201099.4%). The pooled false\u2010positive rate is 2% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 0.6%\u20107%). The area under the curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) of the summary <jats:styled-content style=\"fixed-case\">HSROC<\/jats:styled-content> was 0.93. Positive predictive value was estimated to 93% and the negative predictive value to 94%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Plasma <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> is a promising tool for surveillance in patients with <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010related <jats:styled-content style=\"fixed-case\">HNSCC<\/jats:styled-content>, that is, <jats:styled-content style=\"fixed-case\">OPSCC<\/jats:styled-content>, and has a high specificity. By recent technical advances and by increasing follow\u2010up blood samples, the sensitivity could likely be improved.<\/jats:p><\/jats:sec>","DOI":"10.1111\/coa.13136","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T22:59:21Z","timestamp":1526425161000},"page":"1242-1249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Circulating human papillomavirus <scp>DNA<\/scp> as a surveillance tool in head and neck squamous cell carcinoma: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6001-8569","authenticated-orcid":false,"given":"K.K.","family":"Jensen","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gr\u00f8nh\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.H.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"von Buchwald","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_9_3_1","first-page":"77","article-title":"New insights into human papillomavirus\u2010associated head and neck squamous cell carcinoma","volume":"33","author":"Boscolo\u2010Rizzo P","year":"2013","journal-title":"Acta Otorhinolaryngol Ital"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.3870"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29254"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104123441503"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.10.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.14694\/EDBK_161309"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29323"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.1937"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12335"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6031793"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-951602"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3628"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032260"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20294"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.03.013"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308859"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.06.0226"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2005.02.022"},{"key":"e_1_2_9_24_1","unstructured":"DoeblerP.Meta\u2010Analysis of Diagnostic Accuracy. 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