HPV16 and HPV58 integrations in cervical cancer and premalignant lesions

Abstract

BACKGROUND: Genomic integration of the high-risk human papillomavirus (HPV) DNA into host genome is an important event in the cervical carcinogenesis from premalignant lesions to invasive cervical cancer. The viral DNA integration usually causes the deletion and/or disruption of HPV E2 gene, leading to the up-regulation of E6/7 viral oncoproteins. However, the prognostic value of the viral DNA integration in the prediction of the progression of premalignant lesions is still controversial. HPV16 and HPV58 are the most prevalent high-risk types found in cervical cancer and premalignant lesions in Chinese women, whereas the viral DNA integration status is unknown. OBJECTIVES: To assess the prevalence of HPV16 and HPV58 integrations in cervical cancer and premalignant lesions, as well as their clinical significance. Methods: Genomic DNAs were extracted from 110 HPV16 positive and 48 HPV58 positive cervical samples. HPV infection and genotyping was detected using INNO-LiPA HPV genotyping test. The integration state of the virus was measured by quantitative real-time fluorescent PCR with specific primers targeting E2 and E6 genes of HPV16 and HPV58, and determined by the E2/E6 ratio. RESULTS: HPV16 integration was detected in over 90% of the samples, counting 20 (95.2%) normal cervical samples, 12 (92.3%) ASCUS/low-grade CIN, 22 (95.7%) high-grade CIN and 53 (100%) cancers. Similarly, viral integration was also observed in most of the HPV58 positive samples (44 of 48, 91.7%), including 86.7% normal cervical samples and ASCUS/low-grade CIN, and 100% high-grade CIN and cancers. The integration status of HPV16/58 did not correlate with disease stages and patient survival. CONCLUSIONS: The HPV viral integration in host genome was a common phenomenon in HPV infected normal and cervical disease cases, suggesting that viral DNA integration may occur early in the cervical lesion progression.