Characteristics of HPV Integration in Cervical Adenocarcinoma and Squamous Carcinoma

Abstract

Abstract Purpose HPV integration usually occur in HPV-related cancer, and is the main cause of cancer. But the carcinogenic mechanism of HPV integration is unclear. The study aims to provide a theoretical basis for understanding the pathogenesis of cervical adenocarcinoma (AC) and cervical squamous carcinoma (SCC). Methods We used HPV capture sequencing to obtain HPV integration sites in AC and SCC, and analyzed cytobands, distribution of genetic and genomic elements, identified integration hotspot genes, and performed pathway analysis. Results The results revealed that the most frequently observed integrated cytoband was 8q24.21 in AC and 21p11.2 in SCC, respectively. The breakpoints in both AC and SCC were more tended to occur within gene regions, compared to intergenetic regions. Compared to SCC samples, AC samples had a higher prevalence of genomic elements. Hotspot genes of HPV integration were STARD3 and ERBB2 in AC, and RNA45S rDNA and MIR3648-1 in SCC, respectively. Conclusion These results suggest that overexpression of viral oncogenes plays a significant role in the carcinogenesis of SCC. In AC, HPV integration may affect hosts’ oncogenes, and the dysregulation of oncogenes primarily contributes to progression of AC. Our analysis highlights STARD3 as a novel candidate biomarker of AC.