Risk stratification of cervical disease using detection of human papillomavirus (HPV) E4 protein and cellular MCM protein in clinical liquid based cytology samples

Stevenson, A., Kavanagh, K., Pan, J., Stevenson, L., Griffin, H., Doorbar, J., Scott, E., Deeny, M., Cuschieri, K. and Graham, S. V. (2018) Risk stratification of cervical disease using detection of human papillomavirus (HPV) E4 protein and cellular MCM protein in clinical liquid based cytology samples. Journal of Clinical Virology, 108, pp. 19-25. (doi:10.1016/j.jcv.2018.08.011) (PMID:30218891) (PMCID:PMC6224362)

Stevenson, A., Kavanagh, K., Pan, J., Stevenson, L., Griffin, H., Doorbar, J., Scott, E., Deeny, M., Cuschieri, K. and Graham, S. V. (2018) Risk stratification of cervical disease using detection of human papillomavirus (HPV) E4 protein and cellular MCM protein in clinical liquid based cytology samples. Journal of Clinical Virology, 108, pp. 19-25. (doi:10.1016/j.jcv.2018.08.011) (PMID:30218891) (PMCID:PMC6224362)

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Abstract

Background: While human papillomavirus (HPV) DNA testing offers high sensitivity for the detection of significant cervical disease, its specificity is suboptimal given the high prevalence of transient HPV infections (CIN1 or less). Biomarkers to identify those suffering from low grade disease from those with high grade disease could save healthcare costs and reduce patient anxiety. Objective: The objective of the present work was to develop and test an immunohistochemistry (IHC)-based dual viral and cellular biomarker strategy which was applicable to liquid based cytology (LBC) samples. Study design: We developed a novel IHC assay for detection of HPV E4 and cellular minichromosome maintenance (MCM) proteins in routinely taken cervical LBC samples using cytospin-prepared slides. The assay was applied to a prospective cohort of Scottish women referred to a colposcopy clinic due to preceding cytological abnormalities. The performance of the biomarkers for detection of clinically insignificant (CIN1 or less) versus significant disease was determined. Results: A total of 81 women were recruited representing 64 cases of <=CIN1 and 28 of CIN2 + . Biomarker performance relative to histopathology outcomes showed high levels of MCM detection was significantly associated with CIN2+ (p = 0.03) while E4 was detected more frequently in <=CIN1 (p = 0.06). Conclusions: Combined detection of a host proliferation marker and a marker of viral gene expression could allow triage of cases of clinically insignificant disease prior to colposcopy. However, there was overlap between distributions of MCM levels in CIN2+ and <=CIN1 suggesting that additional biomarkers would be required for improved specificity. Combined with cytospin-prepared slides this approach could provide a means of risk stratification of disease in low resource settings.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cuschieri, Dr Kate and Stevenson, Mr Andrew and Graham, Professor Sheila and Deeny, Dr Miriam
Authors: Stevenson, A., Kavanagh, K., Pan, J., Stevenson, L., Griffin, H., Doorbar, J., Scott, E., Deeny, M., Cuschieri, K., and Graham, S. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Virology
Publisher:Elsevier
ISSN:1386-6532
ISSN (Online):1873-5967
Published Online:31 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of Clinical Virology 108: 19-25
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
660151Priming Innovative Translational Research - The University of Glasgow Confidence in Concept ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_13063RI CARDIOVASCULAR & MEDICAL SCIENCES