Human papillomavirus (HPV) detection using in situ hybridization in histologic samples: correlations with cytologic changes and polymerase chain reaction HPV detection

Abstract

Although in situ hybridization (ISH) and polymerase chain reaction (PCR) have extensively been used on cytology specimens, there have been limited reports of the usefulness of these techniques in relation to confirmed histologic findings. In this study, we used PCR and ISH to detect human papillomavirus (HPV) in cytologic and histologic specimens, respectively. By using positive and negative likelihood ratios, we attempted to identify any predictive role of ISH testing alone or in combination with PCR for the development of high-grade histologic lesions (cervical intraepithelial neoplasia [CIN] 2+). In our study, ISH was a useful method for detection of HPV, even in a large fraction of samples with normal cytologic or biopsy findings. We suggest that when used together and evaluated in conjunction with histologic sections, ISH is a useful tool for ancillary molecular testing of HPV infection in cervical lesions, especially in CIN 2+ histological lesions where its analytic sensitivities and specificities were as good as those of PCR testing.

Image 1

A, Cervical intraepithelial neoplasia (CIN) 1 with mild dysplasia and human papillomavirus (HPV) cytopathic effect with diffuse signal pattern of HPV staining (NBT/BCIP substrate with nuclear fast red counterstain, ×100). B, CIN 2 with moderate dysplasia and HPV cytopathic effect with diffuse signal pattern of HPV staining (NBT/BCIP substrate with nuclear fast red counterstain, ×400). C, Endocervical adenocarcinoma. In situ hybridization is positive for high-risk HPV types in rare adenocarcinoma cells and negative in benign endocervical glands. There is moderate dysplasia and HPV cytopathic effect with diffuse signal pattern of HPV staining (NBT/BCIP substrate with nuclear fast red counterstain, ×400).