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Int J Surg Pathol. 2012 Apr;20(2):146-53. doi: 10.1177/1066896911427703. Epub 2011 Nov 21.

Utility of p16, Ki-67, and HPV test in diagnosis of cervical intraepithelial neoplasia and atrophy in women older than 50 years with 3- to 7-year follow-up.

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Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.



Differentiating cervical intraepithelial neoplasia (CIN) from atrophy in postmenopausal women based on morphology alone is challenging. p16 and Ki-67 help distinguish CIN2/3 from atrophy. The goal of this study is to further characterize the utility of p16, Ki-67, and human papillomavirus (HPV) tests in women older than 50 years, particularly in CIN1.


The authors retrospectively identified cervical specimens from three, 1-year time periods. Included were cases from women older than 50 years with benign diagnoses, atrophy, and CIN. Slides were stained with p16 and Ki-67 and graded as positive or negative. Medical records were reviewed for cytology, HPV test, and histopathologic diagnoses from the time of biopsy to 2010.


A total of 97 cervical samples were included. In all, 34 (74%) CIN1 cases were negative for p16 and Ki-67. Of CIN1 cases with positive HPV tests, only 1/10 (10%) had positive p16 staining versus 2/2 (100%) of CIN2/3 cases. Of 39 women with CIN1 who had follow-up data available, 4 (10%) had subsequent histologic progression to CIN2/3 and none developed invasive disease.


In our study, the majority of cases (74%) diagnosed as CIN1 in women ≥ 50 years are negative for p16 and Ki-67 and do not progress to high-grade dysplasia during 3- to 7-year follow-up. A combination of morphology, p16, and Ki-67 on cervical specimens in women older than 50 years, and furthermore, use of these stains on Pap tests in combination with HPV testing may help distinguish CIN from atrophy and reduce unnecessary invasive follow-up testing.

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