Diagnostic Utility of p16INK4a in Cervical Biopsy Specimens from the Michoacán Cervical Cancer Screening Study II (MECCS II): Correlation with HPV Test Results and Cervical Cytology.
Kathryn S Dyhdalo, Andres Chiesa-Vottero, Lucybeth Nieves-Arriba, Suzanne Belinson, Jerome Belinson, Christine N Booth, Jennifer A Brainard. Cleveland Clinic, OH; Preventive Oncology International, Inc., Cleveland Heights, OH
Background: Surgical biopsy is the gold standard for diagnosis of CIN /carcinoma. CIN 2 is the least reproducible of CIN diagnoses. The p16INK4a (p16) immunostain is a useful objective adjunct in diagnosis of CIN 2. We studied the use of p16 in cervical biopsies from women enrollled in MECCS II.
Design: MECCS II was conducted in 2 sites in Michoacán, Mexico. Pts. ages 30-50, non-pregnant, with varied histories of screening, no history of hysterectomy or pelvic irradiation participated. All pts. had direct samples obtained for HPV testing (Qiagen HC2, Gen-Probe Aptima) and a ThinPrep Pap (Hologic). Pts. + on any test were recalled. At the 2nd visit VIA was done to rule out large (>3 quadrants) pre-invasive disease or cancer, colposcopy and biopsy followed using the POI directed and random biopsy protocol (>5biopsies/patient). All HC2 positive subjects eligible by VIA triage were treated with cryotherapy. P16 immunostaining (Cintec) was performed on all CIN biopsies. P16 was considered positive in CIN 2+ when diffuse, strong staining was seen.
Results: 503 pts. with a +HPV test or abnormal Pap were re-called for secondary screening and treatment (34 lost to follow up). 2,350 biopsies were reviewed and many showed marked acute and chronic cervicitis. Table 1 summarizes Pap test results, HPV status and p16 results in patients with CIN 2+. Of 9 patients with CIN 2 and negative p16, 3 were HPV -, 4 had NILM Paps and 5 had CIN 2 in 1 biopsy only. Table 2 shows a comparison of sensitivy, specificity and positive predictive value with and without p16 results.
|Diagnosis||HPV+||HPV-||Pap ≥ ASCUS||NILM/ Unsat Pap||p16+||p16-|
|CIN 3 (n=12)||12||0||9||2/ 1||12||0|
|CIN 2 (n=22)||18||4||15||5/ 2||13||9|
|Screening test||Sensitivity CIN 2+||Specificity CIN 2+||PPV CIN 2+|
|Pap ≥ ASCUS||73.2%||94.9%||22.6%|
|Pap ≥ ASCUS||76.2%||95.0%||24.1%|