Chromosomal biomarkers for detection of human papillomavirus associated genomic instability in epithelial cells of cervical cytology specimens.
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.
Sokolova
Irina
I
Abbott Molecular Inc., 1300 E. Touhy Avenue, Des Plaines, IL 60018, USA. irina.sokolova@abbott.com
Algeciras-Schimnich
Alicia
A
Song
Minghao
M
Sitailo
Svetlana
S
Policht
Frank
F
Kipp
Benjamin R
BR
Voss
Jesse S
JS
Halling
Kevin C
KC
Ruth
Adam
A
King
Walter
W
Underwood
Dawn
D
Brainard
Jennifer
J
Morrison
Larry
L
D052685:Alphapapillomavirus / Q000502:physiology*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D002898:Chromosomes, Human, Pair 8; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D005260:Female; D018628:Gene Dosage; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D014626:Vaginal Smears
D005819:Genetic Markers