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HPV-related Squamous Neoplasia of the Lower Anogenital Tract: An Update and Review of Recent Guidelines

Maniar, Kruti P. MD; Nayar, Ritu MD

doi: 10.1097/PAP.0000000000000035
Review Articles

Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered “intraepithelial neoplasia” terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient’s true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL

The authors have no NIH funding or conflicts of interest to disclose.

Reprints: Kruti P. Maniar, MD, Department of Pathology, Northwestern University, Feinberg Pavilion 7-335, 251 E Huron St, Chicago, IL 60611 (e-mail: All figures can be viewed online in color at http://

© 2014 by Lippincott Williams & Wilkins.