We could no longer remove may render the transgene more susceptible to silencing

The integration not only changes the transcription pattern relevant for the dysregulated expression of the viral oncogenes, but also affects the expression of the host gene with virus genome integration. The integration alters the expression of host genes in integration sites, even if this occurs within the intron sequences. In our study, we identified a broad spectrum of cancerassociated genes in the integration sites and flanking sequence regions. Most of genes in the integration sites were associated with tumor development, and nineteen genes were strongly related to cervical cancer. Some of them act as tumor suppressors or oncogenes. Interestingly, most of them were not reported in previous documents. MiR-34a, an important tumor suppressor, is down-regulated in cervical cancer. It has been reported that oncoprotein E6 of HPV16 and HPV18 can inhibit the expression of tumorsuppressive miR-34a by destabilization of p53 and resulted in cell proliferation. The disruption of miR-34a gene might further interpret the phenomenon of reduced expression of miR-34a in cervical cancer. MSH2 is a DNA mismatch repair protein, and associated with DNA repair pathway. Decreased expression of MSH2 might be a risk factor in the early stage cervical cancer. ROCK2, an important signaling molecule, can promote cervical cancer metastasis by upregulating and activating the expression and function of moesin protein through RhoA/ ROCK2 pathway. Besides the cancer-associated genes, the genes in integration sites and flanking sequence regions might be also beneficial for viral genome integration. FANCM which is a DNA translocase and highly related to DNA replication regulates checkpoint signaling and replication fork progression. Other genes, such as COX6B1 is related to cell apoptosis and ESRRA also have been reported associated with cervical cancer. In addition, among 45 integration events, 13 events led to antisense transcription of the coding sequences, such as PRDX5, EBAG9 and CD28, etc. These integrations were generally deemed of no interest.