The characteristics of HPV integration in cervical intraepithelial cells

Abstract

Cervical cancer is one of the most common malignant tumors in gynecology. Deploying HIVID, a cost-effective technique to detect HPV integration sites, our team had studied the characteristics of HPV integrations in cervical exfoliated cells. Our results indicated that both the sample proportion and the number of HPV integrations gradually increased following the development of cervical lesion. Meanwhile, our data also revealed that there were recurrent genes integrated by HPV in cervical exfoliated cells. Collectively, the HPV integration breakpoints were highly enriched in the intron and promoter regions. Intriguingly, the gene pathway analysis indicated that the HPV-integrated genes were strongly inclined to pathways of metabolism of xenobiotics by cytochrome P450, chemical carcinogenesis and steroid hormone biosynthesis. In conclusion, this study unveiled the HPV integration patterns and the associated recurrent genes in cervical epithelial exfoliated cells. Altogether, our data suggested that the HPV integrations in cervical exfoliated cells might have vital clinical significance, and probably also diagnostic and/or prognostic values in future clinical applications.

Accurate Detection of HPV Integration Sites in Cervical Cancer Samples Using the Nanopore MinION Sequencer Without Error Correction

“…Our data indicated that most of the integration sites exist in the intergenic region of the human genome, concordant with previous studies ( Bodelon et al, 2016 ; Pinatti et al, 2017 ; Brant et al, 2018 ; Koneva et al, 2018 ; Li et al, 2019 ). Since human genome was identified with large portion (∼60%) of intergenic region, our results identified about 40% integration sites located in intergenic region of human genome, which showed no significant difference.…”

“…After enrichment of virus genomic material using this method, the fusion fragment of human and HPV sequence is isolated and further sequenced by NGS. Many studies have used this method to identify large amount of integration sites with good accuracy ( Chandrani et al, 2015 ; Liu et al, 2016a , b ; Li et al, 2018 , 2019 ). Although NGS is powerful for discovering HPV integration sites, the quality of the results relies on many factors including the probe capture efficiency, sequencing depth, and analysis method.…”

High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis

“…However, HPV-associated cancers contain integrated, episomal or episomal/integrated forms of HPV genome at variable number of copies [74,75]. In addition, it seems that integration events occur randomly in the host cell genome, even though specific hot spots have been reported in cervical exfoliated cells [76]. When integration is not detected in carcinomas, other mechanisms account for E6 and E7 overexpression [77][78][79].…”

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions

“…Most of the HPVint studies are focused on carcinomas [ 20 , 29 , 30 , 31 ] where clonal selection for tumor growth has already happened, and an integration event showed several non-PCR duplicates reads. In this study, nevertheless, we analyzed the viral integration in precancerous samples [ 16 , 21 , 47 ] where a new analysis strategy was designed that allows us to identify reads with evidence of the viral integration with presumably high sensitivity ( Figure 1 ). It was found that virtually all samples analyzed presented viral integration (96%) (except one sample of scarce mapped reads).…”