Research ArticlesDetection of HPV-induced Cervical (Pre) Neoplastic Lesions: A Tissue Microarray (TMA) StudyArafa, Mohammad MD; Boniver, Jacques MD, PhD; Delvenne, Philippe MD, PhDAuthor Information Department of Anatomic Pathology and Cytology, GIGA-Cancer, University of Liege, Belgium Supported by the Belgian Fund for Medical Scientific Research, the L. Fredericq Fund, the Centre Anti-Cancéreux près l'Université de Liège, the Marshall Programme of the Walloon Region (Neoangio No. 616476) and the Egyptian Ministry of Higher Education. Philippe Delvenne is a senior Research Associate of the Belgian National Fund for Scientific Research (FNRS). Reprints: Mohammad Arafa, MD, Department of Pathology B35, CHU Sart Tilman, 4000 Liege, Belgium (e-mail: firstname.lastname@example.org). Received for publication November 16, 2007; accepted January 2, 2008 Applied Immunohistochemistry & Molecular Morphology: October 2008 - Volume 16 - Issue 5 - p 422-432 doi: 10.1097/PAI.0b013e318166fd42 Buy Metrics Abstract The aim of this study was to evaluate the usefulness of a panel of biomarkers in the characterization of human papillomavirus (HPV)-induced cervical lesions. Management of these lesions depends on their histologic confirmation. Misinterpretation especially for benign mimics results in a significant diagnostic disagreement. For these reasons, a continuous effort is still needed to discover surrogate markers, which could support the final diagnosis. Archival biopsies of normal ectocervical and endocervical tissues, squamous metaplasia, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma, adenocarcinoma in situ, and adenocarcinoma were retrieved to perform a tissue microarray (TMA). A panel of markers was tested on the TMA obtained slides by in situ hybridization (HPV DNA) and immunohistochemistry (p16, involucrin, Ki-67, and HPV L1 proteins). The sensitivity to detect high-risk HPV DNA increased with lesion's severity. In situ hybridization signals suggesting integrated viral physical status predominated in CIN II/III, squamous cell carcinoma, and glandular (pre) neoplastic lesions. The p16 and Ki-67 protein expression increased from CIN I to CIN III and to infiltrative lesions. Involucrin positivity was better appreciated in well-differentiated diagnostic entities (ectocervix, mature metaplasia, and CIN I). HPV L1 antibody detected the viral capsid protein in a low proportion of CIN I and II. In conclusion, using a panel of cervical biomarkers improves the final reporting of various HPV-induced epithelial lesions. Carefully constructed TMA with single spots of 1-mm diameter are powerful tools, which have a high reliability in representing full tissue sections. © 2008 Lippincott Williams & Wilkins, Inc.