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We investigated the pathological diagnosis by expert consensus with immunohistochemistry and the presence of somatic mutations in recognised tumour genes in HPV\u2010positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin\u2010embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study. These represented different diagnoses made at previous diagnostic review and HPV status. All were suitable for analysis for somatic tumour associated gene mutations. Three pathologists examined H\/E slides and immunohistochemistry for p16, progesterone receptor and p53 and classified the cases. L1 genes from high\u2010risk HPVs and low\u2010risk HPVs were analysed by SPF10 PCR\u2010DEIA\u2010LiPA25 version 1 in whole tissue sections and microdissected tumour and retested by PCR for E6\/E7 genes of hrHPVs if negative. Cases were analysed for microsatellite instability and next\u2010generation sequencing mutation analysis. From the 45 cases, 20 cases of usual CADC were confirmed of which 17 (85%) were HPV\u2010positive in tumour cells. The other 25 cases were reclassified as endometrial, serous, clear\u2010cell and gastric\u2010type adenocarcinomas and all were HPV\u2010negative in tumour cells. Careful retesting for HPV DNA and IHC leads to more accurate identification of HPV\u2010positive usual cervical adenocarcinomas. Endometrioid endometrial adenocarcinomas, other uterine adenocarcinoma with multiple somatic mutations were important in misclassification of HPV\u2010negative cases locally managed as cervical adenocarcinoma, as was gastric\u2010type adenocarcinoma with germline STK11 mutation in East Asia. Few consensuses confirmed HPV\u2010negative usual cervical adenocarcinomas showed somatic tumorigenic mutations also seen in some HPV\u2010positive usual CADC.<\/jats:p>","DOI":"10.1002\/ijc.33124","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T12:55:03Z","timestamp":1590929703000},"page":"2526-2536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Molecular and pathological basis of <scp>HPV<\/scp>\u2010negative cervical adenocarcinoma seen in a global study"],"prefix":"10.1002","volume":"147","author":[{"given":"David","family":"Jenkins","sequence":"first","affiliation":[{"name":"DDL Diagnostic Laboratory  Rijswijk The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-3005","authenticated-orcid":false,"given":"Anco","family":"Molijn","sequence":"additional","affiliation":[{"name":"DDL Diagnostic Laboratory  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