{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:13:17Z","timestamp":1782252797474,"version":"3.54.5"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T00:00:00Z","timestamp":1407801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Z01 CP010124"],"award-info":[{"award-number":["Z01 CP010124"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Dual\u2010stain cytology for p16 and Ki\u201067 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual\u2010stain cytology among 10 newly trained evaluators.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In total, 480 p16\/Ki\u201067\u2013stained slides from human papillomavirus\u2010positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16\/Ki\u201067 cytology. All participants underwent p16\/Ki\u201067 training and subsequent proficiency testing. Reproducibility of dual\u2010stain cytology was measured using the percentage agreement, individual and aggregate \u03ba values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual\u2010stain cytology.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the \u03ba values ranged from 0.65 to 0.81. The combined \u03ba value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual\u2010stain positivity increased with greater numbers of p16\/Ki\u201067\u2013positive cells on the slides.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Good to excellent reproducibility of p16\/Ki\u201067 dual\u2010stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16\/Ki\u201067 dual\u2010stain evaluation can be implemented in routine cytology practice with limited training. <jats:bold><jats:italic>Cancer (Cancer Cytopathol)<\/jats:italic> 2014;122:914\u2013920.<\/jats:bold> \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21473","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T10:56:00Z","timestamp":1407840960000},"page":"914-920","source":"Crossref","is-referenced-by-count":51,"title":["Interobserver reproducibility and accuracy of p16\/<scp>K<\/scp>i\u201067 dual\u2010stain cytology in cervical cancer screening"],"prefix":"10.1002","volume":"122","author":[{"given":"Nicolas","family":"Wentzensen","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Fetterman","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group Regional Laboratory Kaiser Permanente Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Tokugawa","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group Regional Laboratory Kaiser Permanente Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Schiffman","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E.","family":"Castle","sequence":"additional","affiliation":[{"name":"Global Coalition Against Cervical Cancer Arlington Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon N.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Stiemerling","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group Regional Laboratory Kaiser Permanente Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Poitras","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group Regional Laboratory Kaiser Permanente Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lorey","sequence":"additional","affiliation":[{"name":"The Permanente Medical Group Regional Laboratory Kaiser Permanente Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Kinney","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Kaiser Permanente Medical Care Program Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21139"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a1754"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70145-0"},{"key":"e_1_2_7_5_1","article-title":"The clinical impact of using p16INK4a immunochemistry in cervical histopathology and cytology: an update of recent developments [published online ahead of print April 17, 2013]","author":"Bergeron C","year":"2014","journal-title":"Int J Cancer."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70529-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70568-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/678793"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21378"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt235"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.02.033"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20140"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0270"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.11.1500"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22420"},{"key":"e_1_2_7_16_1","first-page":"109","article-title":"A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides","volume":"32","author":"Grabe N","year":"2010","journal-title":"Cell Oncol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061441"}],"container-title":["Cancer 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