TelePAPology vs. Liquid-Based Cervical Cytology: A Comparative Study Evaluating p16 Immunohistochemistry and HPV Testing by Hybrid Capture-2 and In Situ Hybridization
Trang Pham, Carmen Winters, Marilyn Davis, Fang Fan, Ossama Tawfik. Kansas University Medical Center, Kansas City, KS
Background: The etiologic role of HPV in cervical carcinogenesis is well established. p16, an excellent surrogate marker of HPV E7 functional inactivation of retinoblastoma gene protein, is a cyclin-dependent kinase inhibitor and a marker of cell cycle dysregulation. The use of p16 immunohistochemistry (IHC) has been advocated as an adjunct method in evaluating HPV presence in cervical lesions. Cellblock (CB) preparations from residual liquid based (LB) pap samples have been shown to be of diagnostic value. We have demonstrated the feasibility of not only utilizing imaging technology to overcome current limitations by digitizing cytologic specimens from CB preparations (Telepap method), but also to the value of CB preparation as a source of material for HPV in situ testing. In this study we evaluated HPV in situ hybridization (ISH) on CB preparations and compare the results with p16.
Design: 311 H&E stained CB slides prepared from CBs (Hologic, Marlborough, MA) from residual LP samples were analyzed. These included ASCUS (141), LGSIL (117), HGSIL (24), AGUS (15), normal (6), ASC-H (5), adenocarcinoma (2), squamous cell carcinoma (1) cases. Telepap slides were obtained using the Aperio imaging system (Vista, CA). HC-2 testing (QIAGEN, Inc, Valencia, CA) and HPV ISH testing (iVIEW Blue Detection Kit) (Ventana Medical Systems, Tucson, AZ) and p16 IHC were performed on all CB samples. Test performance characteristics of LP and Telepap samples were compared for diagnostic accuracy and HPV and p16 assay performances.
Results: Telepap virtual slides contained optimal amount of material from all cases. Compared to LP diagnoses, fewer ASCUS and LGSIL cases were diagnosed by Telepap method (124 vs. 141 for ASCUS and 94 vs. 117 for LGSIL cases) and more normal cases were diagnosed (41 vs. 6). The total percentage of HPV+/total HPV tests performed on LP and Telepap specimens were 64% and 66%, respectively. Percent HPV+/total HPV tested ASCUS and LGSIL LP cases were 56 and 96%, respectively and in the Telepap cases in was 51 and 84%, respectively. Percent p16+/total p16 tests performed was 35% in all Telepap samples. The percent +p16 cases in each category was 30% ASCUS, 33% LGSIL and 72% of HGSIL.
Conclusions: The concept TelePAPology is suitable for routine cytology, ISH and IHC testing for HPV and other prognostic markers. HPV ISH and p16 IHC testing is feasible, cost effective and practical. Combination of the two tests would ultimately improve diagnostic accuracy leading to better therapeutic decisions.
Monday, March 4, 2013 1:00 PM
Poster Session II # 88, Monday Afternoon