{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:22:09Z","timestamp":1778624529724,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T00:00:00Z","timestamp":1452211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested formalin\u2010fixed paraffin\u2010embedded diagnostic biopsies for p16 immunohistochemistry and HPV\u2010DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010one percent of patients (170 of 801) showed both HPV\u2010DNA and p16\u2010positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV\u2010positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; .0001). Other independent determinants of HPV positivity were tumor site and smoking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the first study to establish geographic variability as an independent risk factor in HPV\u2010positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. \u00a9 2016 The Authors Head &amp; Neck Published by Wiley Periodicals, Inc.\n                      <jats:italic>Head Neck<\/jats:italic>\n                      <jats:bold>38<\/jats:bold>\n                      : E1863\u2013E1869, 2016\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.24336","type":"journal-article","created":{"date-parts":[[2016,1,10]],"date-time":"2016-01-10T11:23:14Z","timestamp":1452424994000},"source":"Crossref","is-referenced-by-count":39,"title":["Geographic variation in human papillomavirus\u2013related oropharyngeal cancer: Data from 4 multinational randomized trials"],"prefix":"10.1002","volume":"38","author":[{"given":"Hisham","family":"Mehanna","sequence":"first","affiliation":[{"name":"Institute of Head and Neck Studies and Education (InHANSE), School of Cancer Sciences University of Birmingham Edgbaston Birmingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Franklin","sequence":"additional","affiliation":[{"name":"Roche Products Ltd, Shire Park Welwyn Garden City United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Compton","sequence":"additional","affiliation":[{"name":"PPD Granta Park Great Abington Cambridge United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Robinson","sequence":"additional","affiliation":[{"name":"Centre for Oral Health Research Newcastle University Newcastle\u2010upon\u2010Tyne United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ned","family":"Powell","sequence":"additional","affiliation":[{"name":"HPV Oncology Group, Institute of Cancer and Genetics, School of Medicine Cardiff University Cardiff United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Biswas\u2013Baldwin","sequence":"additional","affiliation":[{"name":"GSK Uxbridge Middlesex United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vindh","family":"Paleri","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Newcastle upon Tyne Hospitals, NHS Trust, and Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Hartley","sequence":"additional","affiliation":[{"name":"Hall\u2010Edwards Radiotherapy Research Group Old Queen Elizabeth Hospital Birmingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Fresco","sequence":"additional","affiliation":[{"name":"Department of Oncology University Hospitals Coventry and Warwickshire Coventry United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoda","family":"Al\u2010Booz","sequence":"additional","affiliation":[{"name":"Bristol Haematology and Oncology Centre Bristol United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Junor","sequence":"additional","affiliation":[{"name":"Edinburgh Cancer Centre Western General Hospital Edinburgh United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"El\u2010Hariry","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Synta Pharmaceuticals Corp Lexington Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham Edgbaston Birmingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Harrington","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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