{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:13:24Z","timestamp":1777526004393,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Roche Diagnostics, Basel, Switzer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The triage of human papillomavirus (HPV)\u2010positive women is needed to avoid overreferral to colposcopy. p16<jats:sup>INK4a<\/jats:sup> immunostaining is an efficient triage method. p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 dual staining was introduced mainly to increase reproducibility and specificity compared with stand\u2010alone p16<jats:sup>INK4a<\/jats:sup> staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Within a pilot project, HPV\u2010positive women were referred to colposcopy if cytology was abnormal or unsatisfactory or HPV testing was still positive after 1 year. For 500 consecutive women, a slide obtained during colposcopy was immunostained for p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 and independently interpreted by 7 readers without previous experience with dual staining. Four of these readers were experts in cervical pathology and 3 were not. Kappa values for multiple raters, sensitivity, and specificity for cervical intraepithelial neoplasia type 2\u2010positive histology were computed. Because women with normal cytology were underrepresented, estimates for all HPV\u2010positive women were obtained as weighted means of cytology\u2010specific estimates.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The overall kappa for HPV\u2010positive women was 0.70 (95% confidence interval [95% CI], 0.60\u20100.77). Kappa values were not found to be significantly different between expert and nonexpert readers with regard to cervical cytology but were significantly increased (<jats:italic>P<\/jats:italic> =. 0066) after consensus discussion. The overall specificity estimate for HPV\u2010positive women was 64.0% (95% CI, 57.4%\u201070.2%): 66.7% (95% CI, 59.8%\u201073.0%) for experts and 60.5% (95% CI, 59.8%\u201073.0%) for nonexperts. Among women with abnormal cytology, the sensitivity was 85.5% (95% CI, 77.9%\u201090.8%): 85.8% (95% CI, 77.9%\u201091.2%) for experts and 85.1% (95% CI, 76.6%\u201090.9%) for nonexperts.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 immunostaining demonstrated good reproducibility and specificity when triaging HPV\u2010positive women. Dual\u2010staining interpretation can be performed, after short training, even by staff who are not experts in cervical cytology. This allows HPV\u2010based screening with triage to be performed in settings in which such expert staff is not available. <jats:bold><jats:italic>Cancer (Cancer Cytopathol)<\/jats:italic> 2015;123:212\u2013218.<\/jats:bold> \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21511","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T10:55:26Z","timestamp":1419245726000},"page":"212-218","source":"Crossref","is-referenced-by-count":34,"title":["Interpretation of p16<sup>INK4a<\/sup>\/Ki\u201067 dual immunostaining for the triage of human papillomavirus\u2010positive women by experts and nonexperts in cervical cytology"],"prefix":"10.1002","volume":"123","author":[{"given":"Elena","family":"Allia","sequence":"first","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guglielmo","family":"Ronco","sequence":"additional","affiliation":[{"name":"Center for Cancer Epidemiology and Prevention Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Coccia","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Luparia","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigia","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Fiorito","sequence":"additional","affiliation":[{"name":"Unit of Pathology, OIRM S. Anna Hospital, AO City of Health and Science Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Maletta","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Deambrogio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Tunesi","sequence":"additional","affiliation":[{"name":"Center for Cancer Epidemiology and Prevention Turin Italy"},{"name":"Unit of Medical Statistics and Cancer Epidemiology Department of Translational Medicine Center for Cancer Epidemiology and Prevention Piedmont, University of Eastern Piedmont Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Marco","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"},{"name":"Cancer Epidemiology, Center for Experimental Research and Medical Studies, University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gillio\u2010Tos","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"},{"name":"Cancer Epidemiology, Center for Experimental Research and Medical Studies, University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sapino","sequence":"additional","affiliation":[{"name":"Center for Cervical Cancer Screening, AO City of Health and Science Turin Italy"},{"name":"Department of Medical Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Ghiringhello","sequence":"additional","affiliation":[{"name":"Unit of Pathology, OIRM S. 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