title: Comparison of p16INK4A and Hybrid Capture 2 human papillomavirus testing as adjunctive tests in liquid-based gynecologic SurePath preparations.
abstract: p16(INK4a), cyclin-dependent kinase inhibitor, is functionally inactivated in many tumors, including cervical cancer. We compared p16(INK4A) immunocytochemical staining and Hybrid Capture 2 (HCII) on SurePath specimens using tissue biopsies (as the gold standard). Their utility in a spectrum of atypical and preneoplastic lesions, and their ability to accurately identify underlying lesions of CIN II or greater was assessed using biopsy follow-up data. One-hundred and seventeen residual SurePath samples were collected: 43 atypical squamous cells of undetermined significance (ASCUS), 47 low-grade (LGSIL), and 27 high-grade (HGSIL) squamous intraepithelial lesions. Two slides were prepared from each sample; one stained with the SurePath autocyte stain and one immunostained using the CINtec p16(INK4a) Cytology Kit (Dakocytomation). High-risk HPV testing was performed using the HCII DNA test (Digene, Gaithersburg, MD). Available tissue biopsy follow-up data was retrieved. p16(INK4a) was positive in 32.6% (14/43) ASCUS, 46.8% (22/47) LGSIL, and 48.1% (13/27) HGSIL specimens. HCII DNA test was positive in 41.9% (18/43) ASCUS, 78.7% (37/47) LGSIL, and 96.3% (26/27) HGSIL samples. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of p16(INK4a) and HCII were: 58.7% and 89.8%, 58.6% and 34.6%, 69.2% and 72.1%, 47.2% and 64.3%, respectively. In patients with cervical biopsies, the PPV of HCII (92.3%) results for a biopsy with CINII/III was significantly higher than the PPV of p16(INK4a) (52%) (P=0.001). Using liquid-based cytology specimens, HCII is a more sensitive test than p16(INK4a) for detection of abnormal cytology. HCII has a higher PPV than p16(INK4a) for identifying CIN II/III.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. nassar.aziza@mayo.edu
authors.forename: Aziza
authors.initials: A
authors.lastname: Nassar
authors.forename: Katie
authors.initials: K
authors.lastname: O'Reilly
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Momin T
authors.initials: MT
authors.lastname: Siddiqui
mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000737:chemistry* / Q000821:virology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods*; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004279:DNA, Viral