{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:19:06Z","timestamp":1792793946750,"version":"4.5.0"},"reference-count":88,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Cervical cancer is the fourth most common cancer in females. Genome\u2010wide association studies (GWASs) have proposed cervical cancer susceptibility variants at the <jats:italic>HLA<\/jats:italic> locus on chromosome 6p21. To corroborate these findings and investigate their functional impact in cervical tissues and cell lines, we genotyped nine variants from cervical cancer GWASs (rs17190106, rs535777, rs1056429, rs2763979, rs143954678, rs113937848, rs3117027, rs3130214, and rs9477610) in a German hospital\u2010based series of 1122 invasive cervical cancers, 1408 dysplasias, and 1196 healthy controls. rs17190106, rs1056429 and rs143954678\/rs113937848 associated with cervical malignancies overall, while rs17190106 and rs535777 associated specifically with invasive cancer (OR\u2009=\u20090.69, 95% CI\u2009=\u20090.55\u20130.86, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) or adenocarcinomas (OR\u2009=\u20091.63, 95%CI\u2009=\u20091.17\u20132.27, <jats:italic>p<\/jats:italic>\u2009=\u20090.004), respectively. We tested these and one previously genotyped GWAS variant, rs9272117, for potential eQTL effects on 36 gene transcripts at the <jats:italic>HLA<\/jats:italic> locus in 280 cervical epithelial tissues. The strongest eQTL pairs were rs9272117 and <jats:italic>HLA\u2010DRB6<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20091.9x10E\u20105), rs1056429 and <jats:italic>HLA\u2010DRB5<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20092.5x10E\u20104), and rs535777 and <jats:italic>HLA\u2010DRB1<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20092.7x10E\u20104). We also identified transcripts that were specifically upregulated (<jats:italic>DDX39B<\/jats:italic>, <jats:italic>HCP5<\/jats:italic>, <jats:italic>HLA\u2010B<\/jats:italic>, <jats:italic>LTB<\/jats:italic>, <jats:italic>NFKBIL1<\/jats:italic>) or downregulated (<jats:italic>HLA\u2010C<\/jats:italic>, <jats:italic>HLA\u2010DPB2<\/jats:italic>) in HPV+ or HPV16+ samples. In comparison, treating cervical epithelial cells with proinflammatory cytokine \u03b3\u2010IFN led to a dose\u2010dependent induction of <jats:italic>HCP5<\/jats:italic>, <jats:italic>HLA\u2010B<\/jats:italic>, <jats:italic>HLA\u2010C<\/jats:italic>, <jats:italic>HLA\u2010DQB1<\/jats:italic>, <jats:italic>HLA\u2010DRB1<\/jats:italic>, <jats:italic>HLA\u2010DRB6<\/jats:italic>, and repression of <jats:italic>HSPA1L<\/jats:italic>. Taken together, these results identify relevant genes from both the MHC class I and II regions that are inflammation\u2010responsive in cervical epithelium and associate with HPV (<jats:italic>HCP5<\/jats:italic>, <jats:italic>HLA\u2010B<\/jats:italic>, <jats:italic>HLA\u2010C<\/jats:italic>) and\/or with genomic cervical cancer risk variants (<jats:italic>HLA\u2010DRB1<\/jats:italic>, <jats:italic>HLA\u2010DRB6<\/jats:italic>). They may thus constitute important contributors to the immune escape of precancerous cells after HPV\u2010infection.<\/jats:p>","DOI":"10.1111\/tan.15597","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T10:13:03Z","timestamp":1722852783000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Validation and functional follow\u2010up of cervical cancer risk variants at the <scp>HLA<\/scp> locus"],"prefix":"10.1111","volume":"104","author":[{"given":"Rieke","family":"Eisenbl\u00e4tter","sequence":"first","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finja","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover 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