Integration of human papillomavirus correlates with high levels of viral oncogene transcripts in cervical carcinogenesis

A prospective, cross-sectional study was conducted to investigate the correlation between the integration of high-risk human papillomavirus and disease severity of cervical lesions. 720 liquid-based cytology specimens including 422 normal cytology, 78 low-grade squamous intraepithelial lesions, 172 high-grade squamous intraepithelial lesions, and 48 women with cervical cancers were examined using HPV blot and type-specific E6 PCR. Positive HPV DNA types 16, 18, 52 and 58 were examined for viral DNA using real-time PCR. Expression of E6 transcripts was 89.5% (pure integration), 71.7% (mixed type), and 47.1% (pure episomal) (p<0.0001). Geometric mean levels ranged from 110.6 (episomal form) to 508.4 (mixed form), and 5966.2 (integration form) by real-time PCR (p<0.0001). Geometric mean levels of E6 transcript in HPV 16, 18, 52, and 58 correlated with the severity of cervical lesions and the physical integration state of the viral genome (p<0.0001). We conclude that this is the first paper to point out that integration of high-risk HPVs not only 16 and 18 but also 52 and 58 is correlated with high levels of oncogene transcripts from normal cervix, CIN to cervical cancer.