{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:52:37Z","timestamp":1775267557572,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T00:00:00Z","timestamp":1381536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p><jats:italic>p16<jats:sup>INK4A<\/jats:sup><\/jats:italic> is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16<jats:sup>INK4A<\/jats:sup> as a marker for the risk of low\u2010grade CIN (CIN1) progression. We investigated the prevalence of p16<jats:sup>INK4A<\/jats:sup> immunostaining by CIN grade and whether overexpression of <jats:italic>p16<jats:sup>INK4A<\/jats:sup><\/jats:italic> in CIN1 predicts future risk for high\u2010grade CIN in Chinese women. 6,557 Chinese women aged 30\u201349 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16<jats:sup>INK4A<\/jats:sup> Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2\u2010year interval. The prevalence of p16<jats:sup>INK4A<\/jats:sup> staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (<jats:italic>p<\/jats:italic> &lt; 0.001). HPV positivity was strongly associated with p16<jats:sup>INK4A<\/jats:sup> staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2\u201331.6]. p16<jats:sup>INK4A<\/jats:sup> staining of CIN1 biopsies at baseline was associated with an increased risk of finding high\u2010grade CIN over 2 years of follow\u2010up (OR = 1.43; 95% CI: 0.52\u20133.91). The two\u2010year cumulative incidence of CIN2+ for p16<jats:sup>INK4A<\/jats:sup> positive women was higher at 10.71% than for p16<jats:sup>INK4A<\/jats:sup> negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02\u201366.62). <jats:italic>p16<jats:sup>INK4A<\/jats:sup><\/jats:italic> overexpression is strongly associated with grade of CIN and risk of progression to high\u2010grade CIN in women with low\u2010grade lesions.<\/jats:p>","DOI":"10.1002\/ijc.28485","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T16:50:31Z","timestamp":1381251031000},"page":"1715-1724","source":"Crossref","is-referenced-by-count":54,"title":["p16<sup>INK4A<\/sup> immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: A prospective study in China"],"prefix":"10.1002","volume":"134","author":[{"given":"Guang\u2010Dong","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics The West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education Chengdu China"},{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Sellors","sequence":"additional","affiliation":[{"name":"PATH Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Kui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Ping","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose","family":"Jeronimo","sequence":"additional","affiliation":[{"name":"PATH Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang\u2010Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Rong","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics The West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You\u2010Lin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology Cancer Institute\/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 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