Assessing the detection of human papillomavirus late mRNA in liquid base cytology samples for risk stratification of cervical disease

Chambers, G., Millan, D., Cuschieri, K., Cubie, H.A. and Graham, S.V. (2014) Assessing the detection of human papillomavirus late mRNA in liquid base cytology samples for risk stratification of cervical disease. Journal of Medical Virology, 86(4), pp. 627-633. (doi: 10.1002/jmv.23793) (PMID:24142394) (PMCID:PMC4282440)

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Abstract

Molecular human papillomavirus (HPV) testing is an important and developing tool for cervical disease management. However there is a requirement to develop new HPV tests that can differentiate between clinically significant and benign, clinically insignificant infection. Evidence would indicate that clinically significant infection is linked to an abortive HPV replication cycle. In particular the later stages of the replication cycle (i.e., production of late messenger (m) RNAs and proteins) appear compromised. Compared to current DNA-based tests which indicate only presence or absence of virus, detecting virus mRNAs by reverse transcriptase PCR (RT-PCR) may give a more refined insight into viral activity and by implication, clinical relevance. A novel quantitative (q)RT-PCR assay was developed for the detection of mRNAs produced late in the viral replication cycle. Initially this was validated on HPV-containing cell lines before being applied to a panel of 223 clinical cervical samples representing the cervical disease spectrum (normal to high grade). Samples were also tested by a commercial assay which detects expression of early HPV E6/E7 oncoprotein mRNAs. Late mRNAs were found in samples associated with no, low and high grade disease and did not risk-stratify HPV infection. The data reveal hidden complexities within the virus replication cycle and associated lesion development. This suggests that future mRNA tests for cervical disease may require quantitative detection of specific novel viral mRNAs.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Professor Sheila and Chambers, Dr George and Cuschieri, Dr Kate
Authors: Chambers, G., Millan, D., Cuschieri, K., Cubie, H.A., and Graham, S.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Medical Virology
Publisher:Wiley
ISSN:0146-6615
ISSN (Online):1096-9071
Published Online:19 October 2013
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in the Journal of Medical Virology 84(4):627-633
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
474021Investigating high risk HPV late mRNAs present in tissues isolated from patients with cervical lesions for development of new diagnostic proceduresSheila GrahamScottish Executive Health Department (SEHHD-CSO)CZB/4/632MVLS III - CENTRE FOR VIRUS RESEARCH