Chromosomal biomarkers for detection of human papillomavirus associated genomic instability in epithelial cells of cervical cytology specimens

Irina Sokolova, Alicia Algeciras-Schimnich, Minghao Song, Svetlana Sitailo, Frank Policht, Benjamin R. Kipp, Jesse S. Voss, Kevin C. Halling, Adam Ruth, Walter King, Dawn Underwood, Jennifer Brainard, Larry Morrison

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35 Scopus citations

Abstract

The goal of this study was to compare how accumulation of chromosomal aberrations in human papillomavirus (HPV)-infected cells correlates with the severity of cervical dysplastic lesions. We assessed the frequency of genomic alterations for 35 different loci in a pilot biopsy study and selected two loci (3q26 and 8q24) with the highest frequency of copy number gains found in high-grade dysplasia and cancer. These probes were labeled with gold and red fluorophores and combined with HPV biotin-labeled probes for subsequent detection using a tyramide signal amplification system with a green fluorophore. Cells that were both HPV positive and chromosomally abnormal were designated as "double-positive cells." Cervical cytology specimens from 235 patients were used for this blinded study. The average number of double-positive cells increased from two cells in patients with a cytological interpretation of atypical squamous cells of undetermined significance to 22 cells in low-grade squamous intraepithelial lesion and 99 cells in high-grade squamous intraepithelial lesion, reflecting an accumulation of chromosomal abnormality with disease progression. Using a cutoff of four or more double-positive cells as the criterion for the presence of a cervical intraepithelial neoplasia 2 or 3 lesion, we demonstrated that low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion cytology specimens with underlying cervical intraepithelial neoplasia 2/3 histology showed positive test results in more than 80% of cases. Correlation of 3q26 and 8q24 aneusomy with concurrent HPV infection may thus serve as a biomarker of genetic instability in HPV-infected cells.

Original languageEnglish (US)
Pages (from-to)604-611
Number of pages8
JournalJournal of Molecular Diagnostics
Volume9
Issue number5
DOIs
StatePublished - Nov 2007

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ASJC Scopus subject areas

  • Molecular Biology

Cite this

Sokolova, I., Algeciras-Schimnich, A., Song, M., Sitailo, S., Policht, F., Kipp, B. R., Voss, J. S., Halling, K. C., Ruth, A., King, W., Underwood, D., Brainard, J., & Morrison, L. (2007). Chromosomal biomarkers for detection of human papillomavirus associated genomic instability in epithelial cells of cervical cytology specimens. Journal of Molecular Diagnostics, 9(5), 604-611. https://doi.org/10.2353/jmoldx.2007.070007