{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:00:15Z","timestamp":1792699215424,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>p16 is a sensitive surrogate marker for transcriptionally active high\u2010risk human papillomavirus (HR\u2010HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR\u2010HPV infection by mRNA <jats:italic>in\u2010situ<\/jats:italic> hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR\u2010HPV was detected in 83 of 108 ECA cases (77%), including five HPV\u2010associated adenocarcinomas <jats:italic>in situ<\/jats:italic> and 78 invasive HPV\u2010associated adenocarcinomas. All 83 HPV\u2010positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV\u2010independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV\u2010independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR\u2010HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR\u2010HPV infection correlated with better prognosis among invasive ECAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR\u2010HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15169","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T09:44:35Z","timestamp":1709718275000},"page":"1178-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Immunohistochemical p16 overexpression and Rb loss correlate with high\u2010risk human papillomavirus infection in endocervical adenocarcinomas"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-969X","authenticated-orcid":false,"given":"Nobuko","family":"Yasutake","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Gynecology and Obstetrics Japan Community Healthcare Organization Kyushu Hospital  Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-6445","authenticated-orcid":false,"given":"Hidetaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Science Okayama University  Okayama Japan"},{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Kuga","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Otorhinolaryngology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-6870","authenticated-orcid":false,"given":"Rina","family":"Jiromaru","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0395-8946","authenticated-orcid":false,"given":"Takahiro","family":"Hongo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-3923","authenticated-orcid":false,"given":"Kenzo","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics National Kyushu Cancer Center  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-8993","authenticated-orcid":false,"given":"Hideaki","family":"Yahata","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoko","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-1182","authenticated-orcid":false,"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F"},{"key":"e_1_2_9_3_1","first-page":"336","volume-title":"Tumours of the uterine cervix. 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