Cervical cancer is the second most common
cancer and the third leading cause of
cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-
HPV) infection causes
cervical cancer and precancerous
cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into the host
chromatin is an important step in cervical
carcinogenesis. The detection of integrated papillomavirus sequences-PCR (
DIPS-PCR) allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed
DIPS-PCR for 4 cell lines including 3
cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1 (2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH) to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC) to determine the
protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and
FHIT protein expression levels showed significant decreases when CIN transitioned to
cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and
cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve) analysis to evaluate the potential of all these indexes in distinguishing CIN and
cervical cancer, and the HPV copy number, FHIT copy number and
FHIT protein expression levels have good diagnostic efficiencies.