Evidence map›Paper›PMID 30218891›Full record

ArticleJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology2018

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

Andrew Stevenson, Kim Kavanagh, Jiafeng Pan, Lynne Stevenson, Heather Griffin, John Doorbar, Evelyn Scott, Miriam Deeny, Kate Cuschieri, Sheila V Graham

Open access · hybridAbstract read
In one paragraph

Article in Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. p16International journal of cancer · 2025
    Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 1 country.

Andrew StevensonMRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow, G61 1QH, Scotland, UK. Electronic address: Andrew.Stevenson.2@gla.ac.uk.
Kim KavanaghMathematics and Statistics, Livingstone Tower, University of Strathclyde, Glasgow G1 1XQ, Scotland, UK. Electronic address: Kim.Kavanagh@strath.ac.uk.
Jiafeng PanMathematics and Statistics, Livingstone Tower, University of Strathclyde, Glasgow G1 1XQ, Scotland, UK. Electronic address: Pan.Jiafeng@strath.ac.uk.
Lynne StevensonVeterinary Diagnostic Services, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow, G61 1QH, Scotland, UK. Electronic address: Marion.Stevenson@gla.ac.uk.
Heather GriffinDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. Electronic address: hmg36@cam.ac.uk.
John DoorbarDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. Electronic address: jd121@cam.ac.uk.
Evelyn ScottStobhill Hospital, 133 Balornock Rd, Glasgow G21 3UW, Scotland, UK.
Miriam DeenyStobhill Hospital, 133 Balornock Rd, Glasgow G21 3UW, Scotland, UK. Electronic address: Miriam.Deeny@ggc.scot.nhs.uk.
Kate CuschieriScottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, Scotland, UK. Electronic address: Kate.Cuschieri@nhslothian.scot.nhs.uk.
Sheila V GrahamMRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow, G61 1QH, Scotland, UK. Electronic address: Sheila.Graham@gla.ac.uk.
MRC University of Glasgow Centre for Virus Research · GBStobhill Hospital · GBUniversity of Cambridge · GBUniversity of Strathclyde · GBNHS Lothian · GBUniversity of Glasgow · GB

Funding

Medical Research Council MC_PC_13050Medical Research Council MC_PC_13063Medical Research Council MC_UU_12014/3
6 · The paper itself

Abstract

backgroundWhile 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.

objectiveThe 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

designWe 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.

resultsA 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).

conclusionsCombined 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.

Indexed as

Cytological TechniquesAdultBiomarkersCervix UteriCohort StudiesEarly Detection of CancerFemaleHumansImmunohistochemistryMiddle AgedMinichromosome Maintenance ProteinsOncogene Proteins, ViralPapillomaviridaePapillomavirus InfectionsProspective StudiesRisk AssessmentBiomarkersMinichromosome Maintenance Proteinsoncogene protein E4, Human papillomavirus type 16Oncogene Proteins, ViralBiomarkersCervical intraepithelial neoplasiaCytospinHPVLiquid based cytology

Identifiers

PMID30218891
PMCPMC6224362
OpenAlexW2889501946

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.