Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm

Since the discovery of human papillomavirus (HPV) type 16 in early 80’s, 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 over-treatment 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 anatomical site where the large majority of HPVrelated
(pre)neoplastic lesions develop. These cells appear 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.