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J Gynecol Oncol. 2008 Sep;19(3):162-8. doi: 10.3802/jgo.2008.19.3.162. Epub 2008 Sep 30.

Expression of the p16 and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection.

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  • 1Women's Cancer Clinic, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.



The purposes of this study were to evaluate the expression of p16(INK4a) (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers.


We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopy-directed biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV.


The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007).


CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.


Cervical intraepithelial neoplasia; HPV 16; HPV 58; Ki-67; p16

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