Utility of p16 Immunohistochemistry in Evaluating Negative Cervical Biopsies Following High-Risk Pap Test Results
Alana F Shain, Shirley Kwok, Christina S Kong. Stanford University, Stanford, CA
Background: The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions (LAST) recommends p16 immunohistochemical staining as an adjunct to morphologic assessment of cervical biopsies interpreted as negative from patients that are at high risk for missed high-grade disease (defined as a prior cytologic interpretation of HSIL, ASC-H, ASC-US/HPV-16+, or AGC-NOS) (Darragh, 2012). However, to our knowledge no studies have specifically evaluated the utility of performing p16 on negative cervical biopsies and endocervical curettage specimens following high-risk Pap test results.
Design: A search of Pap test cases from 7/1/2002-12/31/2009 for the term “HSIL” yielded 907 cases with diagnoses of ASC-H, HSIL, and “LSIL cannot exclude HSIL” (AGC-NOS and Atypical Endocervical Cells were secondary diagnoses). 478 cases had tissue follow-up. Cases were excluded if the biopsy was diagnosed as atypical, LSIL, HSIL, or insufficient, or if the time to follow up was >1 year. Immunostain for p16 (CINtec) was performed on 113 cases (91 ASC-H, 22 HSIL) from 106 patients (age 39.6+/-13.1 years) and scored as positive (diffuse strong) or negative. For the positive cases, the corresponding H&E section was re-examined and HPV in situ hybridization (ISH) (Ventana HPV III probe) was performed; follow-up data was also obtained.
Results: Strong p16 staining was seen in 7/106 patients (6.6%) corresponding to missed diagnoses of LSIL (2 cases), HSIL (CIN2, 1 case), and SIL-indeterminate grade (3 cases). One case exhibited staining of bland metaplastic cells undermining endocervical glands; follow-up biopsies showed HSIL. Of 21 patients with a prior HSIL Pap test, 2 (9.5%) had p16(+) biopsies that were also HPV ISH(+). Of 85 patients with prior ASC-H, 2 (2.4%) had p16(+) biopsies and HSIL on follow-up.
|CASE||AGE (YRS)||PRIOR PAP||HPV ISH||REVISED BIOPSY DIAGNOSIS||FOLLOW-UP|