Predictive role of histological features and Ki67 pattern on high-risk HPV presence in atypical cervical lesions.

The most frequently detected alterations of squamous cervical epithelia consist of metaplastic/reactive conditions and human papillomavirus (HPV)-related dysplastic lesions. These latter are traditionally identified as cervical intraepithelial neoplasia (CIN1, 2 or 3) or, in the Bethesda System, as low-grade squamous intraepithelial lesions (LSIL), including CIN1, and high-grade SIL, including CIN2 and CIN3. Some HPV-induced lesions, which are not characterized by obvious dysplasia, are often diagnosed as LSIL. In these lesions, which are hereafter referred to as cervical atipical lesions (CAL), histological features of HPV infection (namely, koilocytosis, multinucleation, acanthosis, papillomatosis, parakeratosis, individual cell keratinization, mitoses in the lower basal third of the epithelium, hyperplasia of basal layers and absence of distinct basal cell layer) can be either inconsistently present or only mildly/focally evident, raising the question of differential diagnosis between HPV-associated changes and repair/reactive or metaplastic changes. In addition, cervical reactive/metaplastic conditions and LSIL can also be contemporaneously present, making the diagnosis even more challenging. Of note, a clear trend to over-diagnose normal, metaplastic or reactive cervical epithelium as HPV-associated LSIL has been reported, leading to therapeutic, reproductive, sexual and social consequences. To improve the diagnosis and management of CAL, it is important to identify among them those lesions that are HPV associated, mainly those harbouring high-risk (HR)-HPV.