Comprehensive Analysis Of HPV Integration In Cervical Cancer Identifies Some New Genomic Hot Spots And Tumor-relevant Genes

Cervical cancer is responsible for 10–15% of cancer-related deaths in women worldwide.Persistent infection with high-risk type human papillomavirus(HR-HPV)is a necessary causal factor in the pathogenesis of cervical carcinoma and integration of HPV into the host genome is regarded as a determining event in cervical carcinogenesis.However,the exact mechanism for integration,and the role of integration in stimulating cancer progression,is not fully characterized.Given this need,the goal of this study was to search for possible common denominators of the integration sites of HPV DNA and to analyse the adjacent cellular sequences.We performed whole-genome sequencing in 13 primary cervical cancer samples,utilized the chromosomal coordinates of 869 breakpoints,and examined for statistical overrepresentation of integration sites with various features of chromatin information data.Analysis of the integration sites in the human genome revealed that there were several integration hotspots such as 14q32,10p15 and 2q37,although all chromosomes were represented.Furthermore,it revealed that HPV DNA preferred to integrate into intragenic regions and gene-dense regions of human chromosomes.Intriguingly,vast host cellular genes affected by the integration sites were found to be cancer-related,for instance,NET1,TUBAL3 and UCN3.The integration-targeted cellular genes identified were also found to be enriched in tumor-related terms and pathways using gene ontology and KEGG analysis.The results expand on knowledge on HPV integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.