Cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN) has been traditionally defined as a continuum of intraepithelial squamous abnormalities which exhibit nuclear atypia in all epithelial layers and possess some potential for progression to invasive carcinoma if not removed. Efforts to subdivide this spectrum into categories of low and high cancer risk have been based previously on the strong association between CIN III (carcinoma in situ) and subsequent invasive carcinoma. However, in practice, this distinction has been discouraged because CIN I and II may be associated with CIN III and a small proportion may progress to invasive carcinoma. As human papillomaviruses (HPV) have emerged as potential markers for subdividing precursor lesions, so-called "high-risk" HPV types have been associated with all grades of CIN, whereas "low-risk" HPV types have segregated primarily in lesions closely resembling condylomata. The place of condyloma in the spectrum of CIN, as well as the precise definition of CIN I, has been controversial. Some authors distinguish condyloma from CIN I and other use similar criteria for the diagnosis of both. Currently, the trend among pathologists and cytopathologists is to classify CIN I as a process either identical to or closely resembling condyloma (low-grade), and CIN II and III as lesions falling within the spectrum of CIN as classically described (high-grade). As new etiologic perspectives (HPV), classifications (Bethesda) and outpatient managements (LEEP) evolve, morphologic definitions of CIN will remain important to patient care, particularly if management decisions are based on nuances of histologic or cytologic grade. When using cervical lesion morphology as an endpoint in chemoprevention studies, investigators must understand that "morphologic progression" of CIN may not be synonymous with biologic progression, that discrepancies between HPV type and morphology exist, and that cytology and histology provide variable, and at times conflicting, information.