Abstract
One of the most frequent challenges in routine diagnostic assessment of cervical biopsies consists of some lesions in which histological features of HPV infection are either inconsistently present or only mildly/focally evident. We named them Atypical Lesions (AL) because differential diagnosis with metaplastic/reactive lesions and LSIL is difficult. It would be important to identify among them those lesions that are really HPV-associated. We studied 52 AL cases to evaluate whether the morphological features and the proliferation index, assessed by Mib1 (Ki67) immunostaining, would be useful to better understand the real nature of AL, with relation to the HPV presence and to the proliferative activity HPV induced. By univariate analysis, koilocytosis was found to be the only relatively sensitive and specific morphologic parameter associated with HPV status (74% sensitivity, 72% specificity, 77.0% PPV). Mib1 index was not proven to be either a sensitive or a specific method (40.7% sensitivity, 64.0%, specificity and 55.0% PPV). Nevertheless, when AL were stratified by the three investigated features (koilocytosis, Mib1 immunostaining and HPV-DNA presence), they could be divided in subgroups consisting of normal cases (lacking of all the three studied features) reactive/repair changes, mimics of koilocytosis, latent, sub-clinical infection, cytopathic infection, without replicative activity (all of them at least lacking of one of the studied features) and finally, proliferative infection cases, in which all the three features were present. The last group showed high probability to harbour HR-HPV DNA (91% of cases). In conclusion, AL appear as a very heterogeneous group of lesions, in which Mib1 assessment alone is not sensitive and specific enough to distinguish HPV negative from HPV positive lesions. Nevertheless, the Mib1 together with koylocitosis, could be useful to identify cases with HPV infection and increased proliferative activity that are at high risk of harbouring HR-HPV DNA and that could have a greater clinical rilevance.
Highlights
The most frequently detected alterations of squamous cervical epithelia consist of metaplastic/reactive conditions and human papillomavirus (HPV)-related dysplastic lesions, these latter being traditionally identified as cervical intraepithelial neoplasia CIN1, 2 or 3[1]
HPV associated lesions have been classified in the Bethesda System as Low-grade Squamous Intraepithelial Lesions (LSIL), which include CIN1 lesions and High-grade SIL (HSIL), which include CIN2 and CIN3
One likely reason is that experienced histopathologists sometimes diagnose as LSIL some less striking HPV-induced lesions, which are not characterized by clear dysplasia and should not be considered as CIN[10]
Summary
The most frequently detected alterations of squamous cervical epithelia consist of metaplastic/reactive conditions and human papillomavirus (HPV)-related dysplastic lesions, these latter being traditionally identified as cervical intraepithelial neoplasia CIN1, 2 or 3[1]. HPV associated lesions have been classified in the Bethesda System as Low-grade Squamous Intraepithelial Lesions (LSIL), which include CIN1 lesions and High-grade SIL (HSIL), which include CIN2 and CIN3. One likely reason is that experienced histopathologists sometimes diagnose as LSIL some less striking HPV-induced lesions, which are not characterized by clear dysplasia and should not be considered as CIN[10]. From the colposcopical point of view, both AL and metaplastic/reactive lesions and LSIL appear like acetowhite foci, which are usually bioptised and represent one of the most frequent challenges in routine surgical pathology practice
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