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Laboratory Management of Cervical Intraepithelial Neoplasia: Proposing a New Paradigm

Herfs, Michael PhD; Crum, Christopher P. MD

Advances In Anatomic Pathology: March 2013 - Volume 20 - Issue 2 - p 86–94
doi: 10.1097/PAP.0b013e3182862aab
Review Articles

Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

*Department of Pathology, Division of Women’s and Perinatal Pathology, Brigham and Women’s Hospital, Boston, MA

Department of Pathology, GIGA-Cancer, University of Liege, Liege, Belgium

The authors declare no conflict of interest or NIH funding sources.

All figures can be viewed online in color at

Reprints: Christopher P. Crum, MD, Department of Pathology, Amory 3, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 (e-mail:

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