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. (C) 2011 Elsevier B.V. All rights reserved.