{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T21:23:56Z","timestamp":1780608236467,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"EPIGENOMICS FLEGSHIP PROJECT- EPIGEN","award":["08934412"],"award-info":[{"award-number":["08934412"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:p>Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure,<jats:italic>EGFR<\/jats:italic>\/<jats:italic>KRAS<\/jats:italic>mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in<jats:italic>EGFR<\/jats:italic>signalling. HPV\u2010DNA detection was performed by<jats:italic>in\u2010situ<\/jats:italic>hybridisation and LINE\u20101 methylation was quantitatively determined by bisulphite\u2010pyrosequencing. High\u2010risk HPV was observed only in 13% of ISP\u2010associated SCC and in 8% of<jats:italic>de novo<\/jats:italic>\u2010SCC patients.<jats:italic>EGFR<\/jats:italic>mutations occurred in 72% of ISPs, 30% of ISP\u2010associated SCCs and 17% of<jats:italic>de novo<\/jats:italic>\u2010SCCs. At 5\u2010year follow\u2010up, SCC arose in only 30% (6\/20) of patients with<jats:italic>EGFR<\/jats:italic>\u2010mutated ISPs compared to 76% (13\/17) of patients with<jats:italic>EGFR<\/jats:italic>\u2010wild\u2010type ISP (<jats:italic>p<\/jats:italic>= 0.0044). LINE\u20101 hypomethylation significantly increased from papilloma\/early stage SCC to advanced stage SCC (<jats:italic>p<\/jats:italic>= 0.03) and was associated with occupational exposure (<jats:italic>p<\/jats:italic>= 0.01) and worse prognosis (<jats:italic>p<\/jats:italic>= 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection;<jats:italic>EGFR<\/jats:italic>mutations characterise those ISPs with a lower risk of developing into SCC; LINE\u20101 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.<\/jats:p>","DOI":"10.1002\/ijc.31971","type":"journal-article","created":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T11:44:42Z","timestamp":1541763882000},"page":"1313-1320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal\u2010inverted papilloma to squamous cell 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