Disruption Events in the HPV18 E1 and E2 Genes in Precancerous Cervical Lesions

Human papillomavirus 18 (HPV18) is the second most oncogenic high-risk HPV genotype, after HPV16, and is responsible for about 15% of cervical cancer cases worldwide. The integration of high-risk HPV DNA into the host genome leads to the disruption of the <i>E1</i> and/or <i>E2</i> genes, which is considered a risk factor for viral-induced carcinogenesis. This study examined the disruption events of HPV18 <i>E1</i> and <i>E2</i> genes in precancerous cervical lesions to investigate the rates and sites of gene disruption in the Greek population. The complete <i>E1</i> and <i>E2</i> genes were amplified using three and four overlapping primer sets, respectively. Extensive analysis revealed that the disruption/deletion events of the <i>E1</i> and <i>E2</i> genes were detected in all grades of cytology-determined lesions, with high frequency. <i>E2</i> gene disruption was significantly related to LSIL+ cases (Fisher's exact test, <i>p</i> = 0.022). No significant association was found in the analysis of the <i>E1</i> gene. Additionally, no preferential sites of <i>E1</i>/<i>E2</i> gene disruption were detected. This is the first study to provide evidence of disruption events of the HPV18 <i>E1</i> gene. The data from the current analysis suggest that disruption of the <i>E2</i> gene could be a significant marker for the progression of cytology-determined cervical dysplasia. However, future studies are required to evaluate whether different geographic populations have particular profiles regarding the rates and sites of gene disruption to further determine population-specific biomarkers.