{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:28:31Z","timestamp":1791379711279,"version":"4.3.3"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,8,25]],"date-time":"2011-08-25T00:00:00Z","timestamp":1314230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2012,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Although previous studies have shown that p16<jats:sup>INK4a<\/jats:sup> and Ki\u201067 are sensitive and specific markers for high\u2010grade lesions (\u2265CIN2) on cervical biopsies, limited information is available regarding the performance of a dual\u2010staining approach as a diagnostic adjunct in cervical cytology. We evaluated a dual p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 immunocytochemistry (ICC) assay to determine its sensitivity and specificity versus that of high\u2010risk HPV (HR\u2010HPV) in a US\u2010based pilot cytology study.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>ThinPrep specimens from 122 cervical cytology specimens encompassing 23 negative (NILM), 20 ASC\u2010US, 22 LSIL, 17 ASCH, 22 HSIL, and 18 AGC cases were processed for multiplexed ICC staining using a CINtec Plus Kit. Dual\u2010positive assay results were defined based on the detection of 1 or more epithelial cells that were stained for both p16<jats:sup>INK4a<\/jats:sup> and Ki\u201067 without regard to cellular morphology. HR\u2010HPV testing was performed by multiplex PCR with capillary electrophoresis genotyping.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Dual staining for p16<jats:sup>INK4a<\/jats:sup> and Ki\u201067 was frequently detected in HSIL and AGC but was rarely detected in NILM cases. The HR\u2010HPV assay showed a sensitivity of 76.2% and a specificity of 55.8% for the detection of clinically significant cervical squamous or endometrial lesions. In contrast, the colocalization of p16<jats:sup>INK4a<\/jats:sup> plus Ki\u201067 maintained a high sensitivity of 81.8% and improved specificity to 81.8% for biopsy\u2010confirmed CIN2\/3, endocervical adenocarcinoma, or endometrial adenocarcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Dual staining for p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 immunocytochemistry dramatically increased specificity and maintained high\u2010level sensitivity for the diagnosis of CIN2\/3 or glandular lesions compared with PCR\u2010based testing for HR\u2010HPV. Cancer (Cancer Cytopathol) 2012. \u00a9 2011 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.20188","type":"journal-article","created":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T22:39:02Z","timestamp":1314830342000},"page":"26-34","source":"Crossref","is-referenced-by-count":41,"title":["Immunocytochemical colocalization of p16<sup>INK4a<\/sup> and Ki\u201067 predicts CIN2\/3 and AIS\/adenocarcinoma"],"prefix":"10.1002","volume":"120","author":[{"given":"Meenakshi","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mockler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Akalin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Laurie","family":"Shroyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth R.","family":"Shroyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.11.1500"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.5858\/2003-127-946-FTDFTA"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.02.047"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21844"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2004.02.012"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1174"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPXSVCDZ3D5MZM"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0b013e31817e9ac5"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20078"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910310104"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20061"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.RCT.0000157092.44680.25"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00793-07"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200211000-00001"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200302000-00006"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1996.0042"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4350"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2002.127439"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/dc.20175"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20140"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.02.033"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncy.20188","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.20188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:11:13Z","timestamp":1760299873000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.20188"}},"subtitle":["Pilot studies"],"short-title":[],"issued":{"date-parts":[[2011,8,25]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,2,25]]}},"alternative-id":["10.1002\/cncy.20188"],"URL":"https:\/\/doi.org\/10.1002\/cncy.20188","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,25]]}}}