Biology and evolution of cervical squamous intraepithelial lesions: A hypothesis with diagnostic prognostic implications

Recent advances in the understanding of HPV-associated cervical squamous intraepithelial lesions, specifically with respect to HPV DNA integration into basal cervical epithelial cells, need to be incorporated into strategies for diagnosing and classifying these lesions. The biology and evolution of HPV-associated cervical squamous intraepithelial lesions is reviewed, along with recent developments using tyramide-based in situ hybridization and MIB-1 immunoreactivity. It is proposed that HPV DNA integration into the basal cells of cervical squamous epithelium precedes the transformation of low- into high-grade lesions. The HPV DNA tyramide-based in situ hybridization system may prove to be a powerful diagnostic/prognostic tool in this regard. It is also proposed that the presence of mitoses (especially atypical forms) in the upper layers may be a discriminatory hallmark in the morphologic distinction between low- and high-grade lesions. Further, since the biologic changes manifest between these two lesions are reflected in their respective phenotype, it appears plausible to adopt the Bethesda System two-tiered/binary classification of LGSIL and HGSIL for histopathologic diagnoses.