Morphological analysis of in situ hybridization signals in cervical intraepithelial neoplasia containing human papillomavirus type 16 or 18: Relationship with histological grade and DNA content

Abstract

Among 345 lesions histologically defined as cervical intraepithelial neoplasia (CIN) examined by in situ hybridization (ISH) for the presence of DNA from human papillomavirus (HPV) types 6/11, 16, 18, 31, 33, and 51, a group of 69 lesions (41 low grade and 28 high grade) containing HPV 16 or 18 was further characterized with the following criteria: DNA ploidy and morphological patterns of ISH spots, i.e., punctate or diffuse throughout the nuclei corresponding to integrated or episomal state of HPV DNA, respectively. The highest percentage of aneuploid lesions, the highest diploid index values, and the highest proportion of CIN with punctase ISH signals were associated with high-grade lesions. In addition, punctase ISH signals were also most frequently found in aneuploid CIN. These results underline that punctate ISH signals considered as integrated HPV DNA were preferentially associated with aneuploid and high-grade lesions, and lead to suggest that this later criteria could be used to predict the evolution of a lesion, towards malignancy.