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The Negative Predictive Value of p16INK4a to Assess the Outcome of Cervical Intraepithelial Neoplasia 1 in the Uterine Cervix

Hariri, Jalil M.D.; Øster, Anne M.Sc., Ph.D.

International Journal of Gynecological Pathology: July 2007 - Volume 26 - Issue 3 - p 223-228
doi: 10.1097/01.pgp.0000236942.51840.56

Summary: The immunohistochemical expression of p16INK4a in formalin-fixed and paraffin-embedded histological sections was evaluated in a retrospective study comprising a low-grade group of 100 cases of cervical intraepithelial neoplasia (CIN) 1, a high-grade group of 50 cases of CIN 2 to 3, and a benign group of 50 cases of normal tissue or benign lesions in the uterine cervix. The cases were consecutive within each group and had a minimum follow-up period of 5 years. Positive reaction for p16INK4a was detected in all cases in the high-grade group and in only 3 cases in the benign group. In the low-grade group, a total of 9 cases had to be excluded. The remaining 91 cases in the low-grade group showed positive reaction for p16INK4a in 65 cases (71%), including 23 cases that progressed to a high-grade lesion, 36 cases that revealed normal cytological and/or histological picture during the follow-up period, and 6 cases that persisted as CIN 1. A total of 26 cases (29%) in the low-grade group showed negative reaction for p16INK4a. All but one of these p16INK4a negative cases in the low-grade group had a benign or normal outcome. This case showed a high-grade lesion in the follow-up period and was probably a high-grade lesion from the beginning and so underestimated as CIN 1. These results reveal that the negative predictive value of p16INK4a to predict the outcome of the cases of CIN 1 is as high as 96%, which strongly suggest an important role of p16INK4a in the assessment of this type of lesion.

From the Department of Pathology, Sønderborg Hospital (J.H.); and Dako (A.Ø.), Glostrup, Denmark.

Address correspondence and reprint requests to Jali Hariri, MD, Department of Pathology, Sønderborg Hospital, Sønderborg, Denmark. E-mail:

All figures are available in color at

©2007International Society of Gynecological Pathologists