Abstract
BackgroundThe integration of HR-HPV genome into host DNA is regarded as a key step for the development of cervical cancer. However, HR-HPV genome indeed exists as episome except for integrant. It may be alternative mechanisms in episome-associated carcinogenesis, although, by which HPV 16 episome induces cervical carcinogenesis is unclear now.MethodsNinety-three invasive cervical cancer tissues with HPV16 positive were collected. Viral physical status was calculated from comparing E2 to E6-copies and detection of viral load was made with realtime-PCR using copy numbers of E6. HPV16 E6 mRNA transcript levels were measured by realtime-PCR. The methylation frequency of HPV16 promoter was detected by PCR and pyrosequencing.ResultsIn 93 samples, 21.5% (20/93) presented purely integrated viral genome, 53.8% (50/93) mixed viral genome, and 24.7% (23/93) purely episomal viral genome. Mean E6 expression in samples with purely episomal viral genomes was 7.13-fold higher than that with purely integrated viral genomes. Meanwhile, viral load in samples with purely episomal viral genomes was 4.53-fold higher than that with purely integrated viral genomes. E6 mRNA expression increased with the viral load in purely episomal cases. There were no differences of mean methylation frequency between purely episomal and integrated virus and among five CpG positions of HPV16 promoter for all samples. And there also was no correlation between E6 mRNA expression and methylation of HPV16 promoter among all samples with purely HPV16 episomal virus.ConclusionsHPV16 with the purely episomal viral genomes exists in a definite proportion of invasive cervical cancer, and episomal HPV16 also overexpresses E6 mRNA, probably through a high level of viral load.
Highlights
The integration of HR-human papillomaviruses (HPV) genome into host Deoxyribonucleic acid (DNA) is regarded as a key step for the development of cervical cancer
Li et al [4] reported the existence of HPV 16 integration in all of 15 cases of cervical cancer tissues, but Dutta S et al [5] detected 82% cases contained HPV16 integrant in cervical cancer samples, and Mazumder D and his collogues found that 70.3% samples harbored integration HPV16 in cervical cancer tissue [6]
E6 Messenger Ribonucleic Acid (mRNA) expression was higher in high viral load group than that in low viral load group in purely episomal cases (P = 0.007; Mann–Whitney Test), but E6 mRNA expression was not significantly different between high and low viral load group in purely integrated cases
Summary
The integration of HR-HPV genome into host DNA is regarded as a key step for the development of cervical cancer. HR-HPV genome exists as episome except for integrant It may be alternative mechanisms in episome-associated carcinogenesis, by which HPV 16 episome induces cervical carcinogenesis is unclear now. This phenomenon points toward the biological plausibility of cervical carcinogenesis under the impact of HPV16 episome, in addition to E2 disruption due to viral genome integration into the host genome. It may be alternative mechanisms in episome-associated carcinogenesis, by which HPV 16 episome induces cervical carcinogenesis is unclear
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