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

• Published in: Virus research 2011-11, Vol.161 (2), p.124-130
• Main Authors: Ho, Chih-Ming, Lee, Bor-Heng, Chang, Shwu-Fen, Chien, Tsai-Yen, Huang, Shih-Hung, Yan, Chiu-Cho, Cheng, Weng-Fang
• Format: Article
• Language: English
• Subjects: Adult; Alphapapillomavirus - classification; Alphapapillomavirus - genetics; Alphapapillomavirus - isolation & purification; Alphapapillomavirus - physiology; carcinogenesis; cell biology; Cervical cancer; cervix; Cervix Uteri - pathology; Cervix Uteri - virology; Cross-Sectional Studies; cytology; disease severity; DNA; Female; Gene Expression Regulation, Viral; Human papillomavirus; Humans; Integration; Middle Aged; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; oncogenes; Papillomaviridae; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; PCR; Physical state; Prospective Studies; quantitative polymerase chain reaction; Transcription, Genetic; uterine cervical neoplasms; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Virus Integration; women
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2011.06.012

► The incidence of HPV integration increases from normal cervix, CIN to cervical cancer. ► HPV gene expression reflects the HPV physical state. ► And HPV expression level correlates with the HPV physical state. 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.