Presence of episomal and integrated human papillomavirus DNA sequences in cervical carcinoma

Abstract

Thirty surgical samples of squamous cell carcinoma of the cervix obtained from Chinese women were analysed for the presence of human papillomavirus (HPV) types 16 and 18 using Southern blot hybridization procedure. HPV16 was detected in 53% while HPV18 was found in only 6% of the samples analyzed. When compared with other reports, variation in the geographic distribution of these two HPV types in association with cervical carcinoma is noted. Thirty-seven and a half percent of the HPV16-positive samples contained this HPV type in episomal form and an equal number in cellular DNA-integrated form. The simultaneous presence of both episomal and integrated forms was found in the remaining 25% of the positive samples. The two HPV18-positive cases harbored only episomal viral genome and were not superinfected by HPV16. Analysis of the HPV16 integration samples showed that single integration events had probably occurred and some of the viral sequences had been lost on or subsequent to integration.

The Human Papillomavirus Type 16 E5 Oncoprotein Inhibits Epidermal Growth Factor Trafficking Independently of Endosome Acidification

“…In addition, targeted epithelial expression of 16E5 (without E6 and E7) in transgenic mice induces skin tumors (21). It may be noteworthy that unlike high-risk HPV-18, which integrates into the host DNA and potentially disrupts E5 gene expression (20, 64), the HPV-16 genome often persists in episomal form in malignant lesions (12,16,24,36,42).Biological activities of 16E5 that may facilitate carcinogenesis include evading host immune detection by interfering with the transport of antigen-presenting major histocompatibility complex (MHC) class I molecules to the cell surface (6), promoting anchorage-independent growth (33, 41, 52) and disrupting gap junctions responsible for cell-cell communication (37,58). The 16E5 phenotype most frequently linked to the development of cancer is enhanced ligand-dependent activation of the epidermal growth factor receptor (EGFR) (15,41,46,52).…”

“…In addition, targeted epithelial expression of 16E5 (without E6 and E7) in transgenic mice induces skin tumors (21). It may be noteworthy that unlike high-risk HPV-18, which integrates into the host DNA and potentially disrupts E5 gene expression (20, 64), the HPV-16 genome often persists in episomal form in malignant lesions (12,16,24,36,42).…”

Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa

“…Rather, papilloma virus-mediated oncogenesis requires supplementary genetic changes that occur over time following the initial infection. Whilst it is clear that integration of viral DNA into the host genome is crucial to HPV-induced tumor development (22,23), whether this is a cause or consequence of wider-spread chromosome instability is not clear.…”

Quantitative Measurement of Human Papillomavirus Type 16 E5 Oncoprotein Levels in Epithelial Cell Lines by Mass Spectrometry

“…The same genetic changes that alter E2 expression during viral integration are also believed to disrupt E5 expression (52). It is for this reason that E5 is thought to function mainly during the productive life cycle of the virus (when the viral genome is maintained episomally).Unlike high-risk HPV-18, which is almost exclusively integrated in cervical cancer (18, 64), the HPV-16 genome has been found to persist episomally in 26 to 76% of malignant lesions (9,11,16,22,37,44). Other evidence suggests that 16E5 also may be expressed from integrated viral DNA.…”

“…Unlike high-risk HPV-18, which is almost exclusively integrated in cervical cancer (18, 64), the HPV-16 genome has been found to persist episomally in 26 to 76% of malignant lesions (9,11,16,22,37,44). Other evidence suggests that 16E5 also may be expressed from integrated viral DNA.…”