Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women
| Autor: | Raji Ganesan, Kate Cuschieri, Lawrence S. Young, Ciaran B J Woodman, Sally Roberts, Ramanand Athavale, Merlin Pereira, Sarah Leonard, Gerard J. Nuovo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology Time Factors Physiology Cervix Uteri Polymerase Chain Reaction law.invention Cohort Studies 0302 clinical medicine law Virus latency Medicine In Situ Hybridization Polymerase chain reaction Cervical cancer Human papillomavirus 16 education.field_of_study Multidisciplinary Incidence (epidemiology) virus diseases Middle Aged Virus Latency DNA-Binding Proteins Real-time polymerase chain reaction 030220 oncology & carcinogenesis Population study Female Adult Risk medicine.medical_specialty Population In situ hybridization Hysterectomy Article Fixatives 03 medical and health sciences Formaldehyde Humans education Aged Tissue Embedding business.industry Papillomavirus Infections Oncogene Proteins Viral Cell Transformation Viral medicine.disease 030104 developmental biology Asymptomatic Diseases DNA Viral business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep20847 |
| Popis: | High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life. |
| Databáze: | OpenAIRE |
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