Study On HPV Integration And Genomic Instability In Cervical Cancer

Objective:To study the significance of HPV integration and genomic instability in the development of cervical cancer, we established the HPV integration-FISH technique, investigated HPV integration characteristics of cervical cancer in situ, explored the possibility to use copy number and protein expression of TP63and MYC as progression, as well as gene set enrichment analysis, to reveal the impact of HPV integration and genomic instability on cervical carcinogenesis.Methods:We established a new replicable FISH probes production methods, investigated the frequency of HPV integration in different genomic loci of cervical cancer. Copy numbers of TP63and MYC were investigated by FISH, protein expressions of them were analyzed by IHC. The diagnostic test performance was measured by ROC. We also analyzed cervical squamous cell carcinoma and normal cervical epithelial tissue specimens in GEO database for expression profiling.Results:The new FISH probes production method can effectively detect HPV integration in cervical cancer. The most frequent HPV integration site was8q24locus. The average copy number and expression of TP63and MYC increased in the progression of CIN to cervical cancer. TP63amplification showed good diagnostic performance. ATM signaling pathway is activated in cervical cancer, Chromosome3q region was prone to enrich overexpressed genes.Conclusions:There are high frequent HPV integration sites in cervical cancer. Amplification and overexpression of TP63and MYC, and HPV integration rate are associated with the transition of CIN to cervical cancer. ATM pathway and chromosome3q region activation are major events in cervical cancer. These are all valuable biomarkers in cervical cancer.