Immunocytochemical analysis of the cervical pap smear

Although immunostained cervical Pap smears are not yet FDA approved for clinical use, it is very likely that they will become widely employed in the near future to identify neoplastic squamous and iendocervical glandular cells when screening liquid-based cytological preparations (i.e., SurePath™ or ThinPrep™). The current problem with cytology complemented by high-risk human papillomavirus (HPV) testing is poor specificity. HPV testing provides superior sensitivity, but many women are infected with the virus, while very few have had persistent infections leading to carcinoma. Pathologists routinely use antibodies directed against the cyclin-dependent kinase inhibitor p16 (p16^INK4a) or a combination of antibodies directed against topoisomerase-2-alpha and minichromosome maintenance protein-2 (as in ProEx™ C) to improve diagnostic precision and accuracy in cervical tissue biopsies. This chapter will describe the immunocytochemical methods used by our group to immunostain cervical Pap smears and provide significantly improved positive predictive value when screening for cervical cancer.