Utility of P16, KI67 and HPV Test in Diagnosis of Cervical Intraepithelial Neoplasia and Atrophy in Women over 50 Years of Age with 3-7 Year Follow-Up.
Julie A Jackson, Umesh Kapur, Praba Rajan, Alia Salhadar, Cagatay Ersahin. Loyola University Medical Center, Maywood, IL
Background: Differentiating Cervical Intraepithelial Neoplasia (CIN) from atrophy in postmenopausal women is challenging based on morphology alone. p16 and Ki67 help in distinguishing CIN2/3 from atrophy, and a positive HPV test increases the likelihood of follow-up histologic diagnosis of CIN2/3 in women over age 50. Our goal is to further characterize the utility of p16, Ki-67 and HPV tests in women over age 50, particularly in CIN1.
Design: We retrospectively identified consecutive cervical specimens (biopsy, cone, and LEEP) from three one-year time periods (2003, 2004, and 2007). Included were cases from women ≥ age 50 with benign diagnoses, atrophy, and CIN. Slides were stained with p16 and Ki67. p16 was graded as positive or negative, and Ki67 graded as positive or negative. Medical records were reviewed for cytology, HPV test, and histopathologic diagnoses from time of biopsy to 2010.
Results: 97 cervical samples from 86 women (mean age=57) were analyzed and stained. The reason for sampling was either for follow up of abnormal pap smear in 68 (70%) cases or for other reasons (i.g. abnormal biopsy, postmenopausal bleeding). 34 (74%) of CIN1 cases were negative for both p16 and Ki67 (see table). Of CIN1 cases with positive HPV tests, only 1/11(9%) had positive p16 staining, versus 2/2 (100%) of CIN2/3 cases. 39 women with CIN1 had follow-up data available. Of those, 4 (10%) had subsequent histologic progression to CIN2/3 and none developed invasive disease. Of these four cases, p16 was positive in 1 case, and HPV test was positive in a separate case.