{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:54:24Z","timestamp":1775580864190,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Oesophageal Cancer Research Fund, Sydney, New South Wales, Australia"},{"name":"Kishen Family Trust, Sydney, New South Wales, Australia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,11,15]]},"abstract":"<jats:p>We have previously demonstrated that transcriptionally active high\u2010risk HPV (hr\u2010HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)\/BD\/OAC by immunohistochemical staining (IHC) of formalin\u2010fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6\/E7, respectively. Prospectively, BM (<jats:italic>n<\/jats:italic>\u2009=\u200981)\/BD (<jats:italic>n<\/jats:italic>\u2009=\u200972)\/OAC (<jats:italic>n<\/jats:italic>\u2009=\u200965) FFPE specimens were subjected to IHC staining for pRb, p16<jats:sup>INK4A<\/jats:sup>, cyclin D<jats:sub>1<\/jats:sub>, p53 and RNA <jats:italic>in\u2010situ<\/jats:italic> hybridization for E6\/E7 transcripts. HPV DNA was determined <jats:italic>via<\/jats:italic> PCR in fresh frozen specimens. Viral load measurement (real\u2010time PCR) and Next Generation Sequencing of TP53 was performed. Of 218 patients, 56 were HPV DNA positive [HPV16 (<jats:italic>n<\/jats:italic>\u2009=\u200942), 18 (<jats:italic>n<\/jats:italic>\u2009=\u200913), 6 (<jats:italic>n<\/jats:italic>\u2009=\u20091)]. Viral load was low. Transcriptionally active HPV (DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>+<\/jats:sup>) was only found in the dysplastic and adenocarcinoma group (<jats:italic>n<\/jats:italic>\u2009=\u200921). The majority of HPV DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>+<\/jats:sup> BD\/OAC were characterized by p\n<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/ijc30896-math-0001.png\" xlink:title=\"urn:x-wiley:00207136:media:ijc30896:ijc30896-math-0001\"\/> (14\/21, 66.7%), pRb<jats:sub>low<\/jats:sub> (15\/21, 71.4%) and p53<jats:sub>low<\/jats:sub> (20\/21, 95%) and was significantly different to controls [combination of HPV DNA<jats:sup>\u2013<\/jats:sup>\/RNA<jats:sup>\u2013<\/jats:sup> (<jats:italic>n<\/jats:italic>\u2009=\u200994) and HPV DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>\u2013<\/jats:sup> cohorts (<jats:italic>n<\/jats:italic>\u2009=\u200922)]. p53<jats:sub>low<\/jats:sub> had the strongest association with DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>+<\/jats:sup> oesophageal lesions (OR\u2009=\u200923.5, 95% CI\u2009=\u20092.94\u2013187.8, <jats:italic>p<\/jats:italic>\u2009=\u20090.0029). Seventeen HPV DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>+<\/jats:sup> BD\/OAC identified as p53<jats:sub>low,<\/jats:sub> were sequenced and all but one exhibited wild\u2010type status. pRb<jats:sub>low<\/jats:sub>\/p53<jats:sub>low<\/jats:sub> provided the best balance of strength of association (OR\u2009=\u20098.0, 95% CI\u2009=\u20092.6\u201325.0, <jats:italic>p<\/jats:italic>\u2009=\u20090.0003) and sensitivity (71.4%)\/specificity (71.6%) for DNA<jats:sup>+<\/jats:sup>\/RNA<jats:sup>+<\/jats:sup> BD\/OAC. Active HPV involvement in BD\/OAC is characterized by wild\u2010type p53 and aberrations of the retinoblastoma protein pathway.<\/jats:p>","DOI":"10.1002\/ijc.30896","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T12:10:57Z","timestamp":1500466257000},"page":"2037-2049","source":"Crossref","is-referenced-by-count":28,"title":["Active human papillomavirus involvement in Barrett's dysplasia and oesophageal adenocarcinoma is characterized by wild\u2010type p53 and aberrations of the retinoblastoma protein pathway"],"prefix":"10.1002","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8893-4638","authenticated-orcid":false,"given":"Shanmugarajah","family":"Rajendra","sequence":"first","affiliation":[{"name":"Gastro\u2010Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Sydney NSW Australia"},{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Bankstown\u2010Lidcombe Hospital, South Western Sydney Local Health Network Bankstown, Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology South Western Sydney Area Pathology Service, Liverpool Sydney NSW Australia"},{"name":"Faculty of Medicine Discipline of Pathology, School of Medicine, University of Western Sydney  NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xuan","sequence":"additional","affiliation":[{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"},{"name":"Ingham Institute for Applied Medical Research, Liverpool Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prateek","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Veterans Affairs Medical Center and University of Kansas City  MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Pavey","sequence":"additional","affiliation":[{"name":"Gastro\u2010Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Sydney NSW Australia"},{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Bankstown\u2010Lidcombe Hospital, South Western Sydney Local Health Network Bankstown, Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheong Soon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology South Western Sydney Area Pathology Service, Liverpool Sydney NSW Australia"},{"name":"Faculty of Medicine Discipline of Pathology, School of Medicine, University of Western Sydney  NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Son","family":"Le","sequence":"additional","affiliation":[{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Bankstown\u2010Lidcombe Hospital, South Western Sydney Local Health Network Bankstown, Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine","family":"Collins","sequence":"additional","affiliation":[{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"},{"name":"Department of Gastroenterology &amp; Hepatology Bankstown\u2010Lidcombe Hospital, South Western Sydney Local Health Network Bankstown, Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Gastro\u2010Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Sydney NSW Australia"},{"name":"South Western Sydney Clinical School, University of New South Wales Kensington, Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2009.067447"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.94"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.206"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.11.017"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12881"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206923"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh183"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103411"},{"key":"e_1_2_7_10_1","first-page":"250","article-title":"Human papillomavirus and the risk of Barrett's esophagus","volume":"43","author":"El\u2010Serag HB","year":"2012","journal-title":"Dis Esophagus"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2008.07.004"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2010.11.015"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.1670"},{"key":"e_1_2_7_15_1","first-page":"4620","article-title":"E7 protein of human papilloma virus\u201016 induces degradation of retinoblastoma protein through the ubiquitin\u2010proteasome pathway","volume":"56","author":"Boyer SN","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_7_16_1","first-page":"5","article-title":"Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control","volume":"58","author":"Andl T","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.00.3335"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90409-8"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25479"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.296"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2000.00720.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2007.00489.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2009.02.004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.63"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28142"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27605"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.2904"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2008.08.006"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.7662"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21974"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25174"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205214"},{"key":"e_1_2_7_33_1","first-page":"1633","article-title":"Absence of cyclin D\/cdk complexes in cells lacking functional retinoblastoma protein","volume":"9","author":"Bates S","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.06.008"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318220e59d"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.30896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.30896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T17:48:24Z","timestamp":1696528104000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.30896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,4]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,11,15]]}},"alternative-id":["10.1002\/ijc.30896"],"URL":"https:\/\/doi.org\/10.1002\/ijc.30896","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,4]]}}}