{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T06:48:48Z","timestamp":1785653328668,"version":"3.56.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T00:00:00Z","timestamp":1432080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biokring II VZW","award":["R13-014"],"award-info":[{"award-number":["R13-014"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent high\u2010risk human papillomavirus (<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>) infection is strongly associated with the development of high\u2010grade cervical intraepithelial neoplasia (<jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>) or cancer. Not all persistent infections lead to cancer. Viral load measured at a single time\u2010point is a poor predictor of the natural history of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infections. However the profile of viral load evolution over time could distinguish nonprogressive from progressive (carcinogenic) infections. A retrospective natural history study was set up using a Belgian laboratory database including more than 800,000 liquid cytology specimens. All samples were submitted to <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> identifying E6\/E7 genes of 18 <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> types. Viral load changes over time were assessed by the linear regression slope. Database search identified 261 untreated women with persistent type\u2010specific <jats:styled-content style=\"fixed-case\">HPV DNA<\/jats:styled-content> detected (270 infections) in at least three of the last smears for a average period of 3.2\u00a0years. Using the coefficient of determination (<jats:italic>R<\/jats:italic>\u00b2) infections could be subdivided in a latency group (<jats:italic>n<\/jats:italic>\u00a0=\u00a0143; <jats:italic>R<\/jats:italic>\u00b2\u00a0&lt;\u00a00.85) and a regressing group (<jats:italic>n<\/jats:italic>\u00a0=\u00a0127; <jats:italic>R<\/jats:italic>\u00b2\u00a0\u2265\u00a00.85). In (\u22653) serial viral load measurements, serial transient infections with latency is characterized by a nonlinear limited difference in decrease or increase of type\u2010specific viral load (<jats:italic>R<\/jats:italic>\u00b2\u00a0&lt;\u00a00.85 and slopes between 2 measurements 0.0010 and \u22120.0010\u00a0HPV copies\/cell per day) over a longer period of time (1553\u00a0days), whereas regression of a clonal cell population is characterized by a linear (<jats:italic>R<\/jats:italic>\u00b2\u00a0\u2265\u00a00.85) decrease (\u22120.0033\u00a0HPV copies\/cell per day) over a shorter period of time (708\u00a0days; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Using serial <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> type\u2010specific viral load measurements we could for the first time identify regressing <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">CIN<\/jats:styled-content>3 lesions. Evolution of the viral load is an objective measurable indicator of the natural history of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infections and could be used for future triage in <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010based cervical screening programs.<\/jats:p>","DOI":"10.1002\/cam4.473","type":"journal-article","created":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T06:09:41Z","timestamp":1432102181000},"page":"1294-1302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Serial type\u2010specific human papillomavirus (<scp>HPV<\/scp>) load measurement allows differentiation between regressing cervical lesions and serial virion productive transient infections"],"prefix":"10.1002","volume":"4","author":[{"given":"Christophe E.","family":"Depuydt","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics AML Sonic Healthcare Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jef","family":"Jonckheere","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics AML Sonic Healthcare Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Berth","sequence":"additional","affiliation":[{"name":"Department of Immunology AML Sonic Healthcare Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert M.","family":"Salembier","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics AML Sonic Healthcare Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J.","family":"Vereecken","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics AML Sonic Healthcare Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes J.","family":"Bogers","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics AML Sonic Healthcare Antwerp Belgium"},{"name":"Laboratory for Cell Biology and Histology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02402-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.55.4.244"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)12490-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27650"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2012.01631.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.06.095"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.02.039"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01231-12"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57149"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874357901206010198"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181fe777f"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e318286a95d"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1128\/jvi.65.5.2254-2260.1991","article-title":"Amplification of human papillomavirus genomes in\u00a0vitro is dependent on epithelial differentiation","volume":"65","author":"Bedell M. 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