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Cited by 494Cervical Cancer and HPV ResearchWomen's cancer prevention and managementReproductive tract infections research

The DOI matches its Crossref record; 142 of the 145 references it cites were found in a registry or an index.

Cytology versus HPV testing for cervical cancer screening in the general population

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Koliopoulos, George, Nyaga, Victoria N, Santesso, Nancy, Bryant, Andrew, Martin-Hirsch, Pierre PL, Mustafa, Reem A, Schünemann, Holger, Paraskevaidis, Evangelos, Arbyn, Marc·2017·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd008587.pub2PMC PMC6483676
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Abstract

BACKGROUND: Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and cervical carcinogenesis, HPV testing has been proposed as an alternative screening test. OBJECTIVES: To determine the diagnostic accuracy of HPV testing for detecting histologically confirmed cervical intraepithelial neoplasias (CIN) of grade 2 or worse (CIN 2+), including adenocarcinoma in situ, in women participating in primary cervical cancer screening; and how it compares to the accuracy of cytological testing (liquid-based and conventional) at various thresholds. SEARCH METHODS: We performed a systematic literature search of articles in MEDLINE and Embase (1992 to November 2015) containing quantitative data and handsearched the reference lists of retrieved articles. SELECTION CRITERIA: We included comparative test accuracy studies if all women received both HPV testing and cervical cytology followed by verification of the disease status with the reference standard, if positive for at least one screening test. The studies had to include women participating in a cervical cancer screening programme who were not being followed up for previous cytological abnormalities. DATA COLLECTION AND ANALYSIS: We completed a 2 x 2 table with the number of true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study. We calculated the absolute and relative sensitivities and the specificities of the tests for the detection of CIN 2+ and CIN 3+ at various thresholds and computed sensitivity (TP/(TP + TN) and specificity (TN/ (TN + FP) for each test separately. Relative sensitivity and specificity of one test compared to another test were defined as sensitivity of test-1 over sensitivity of test-2 and specificity of test-1 over specificity of test-2, respectively. To assess bias in the studies, we used the Quality Assessment of Diagnostic test Accuracy Studies (QUADAS) tool. We used a bivariate random-effects model for computing pooled accuracy estimates. This model takes into account the within- and between-study variability and the intrinsic correlation between sensitivity and specificity. MAIN RESULTS: We included a total of 40 studies in the review, with more than 140,000 women aged between 20 and 70 years old. Many studies were at low risk of bias. There were a sufficient number of included studies with adequate methodology to perform the following test comparisons: hybrid capture 2 (HC2) (1 pg/mL threshold) versus conventional cytology (CC) (atypical squamous cells of undetermined significance (ASCUS)+ and low-grade squamous intraepithelial lesions (LSIL)+ thresholds) or liquid-based cytology (LBC) (ASCUS+ and LSIL+ thresholds), other high-risk HPV tests versus conventional cytology (ASCUS+ and LSIL+ thresholds) or LBC (ASCUS+ and LSIL+ thresholds). For CIN 2+, pooled sensitivity estimates for HC2, CC and LBC (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). AUTHORS' CONCLUSIONS: Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment. Evidence from prospective longitudinal studies is needed to establish the relative clinical implications of these tests.

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Research works printed but not linked: 9

  1. McAdam, 2010, Evaluation of a cervical cancer screening program based on HPV testing and LLETZ excision in a low resource setting, PLoS ONE, 5, e13266, 10.1371/journal.pone.0013266 · DOI
  2. Castle, 2011, Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study, Lancet Oncology, 12, 880, 10.1016/S1470-2045(11)70188-7 · DOI
  3. Chan, 1999, NASBA and other transcription-based amplification methods for research and diagnostic microbiology, Review Medical Microbiology, 10, 184
  4. International Agency for research on Cancer, 2005, Cervix Cancer Screening: IARC Handbooks of Cancer Prevention, 10
  5. IARC working group on the evaluation of carcinogenic risks to humans, 2007, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 90: Human Papilloma viruses
  6. Kjaer S Long term predictive value of HPV testing (the Danish prospective cohort study) 21st International Human Papillomavirus Conference Mexico City Abstract 339
  7. Luesley, 2004, NHSCSP Publication No. 20. Colposcopy and Programme Management. Guidelines for the NHS Cervical Screening Programme
  8. Reitsma JB Rutjes AWS Whiting P Vlassov VV Leeflang MMG Deeks JJ Chapter 9: Assessing methodological quality. In: Deeks JJ, Bossuyt PM, Gatsonis C (editors), Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 1.0.0. The Cochrane Collaboration, 2009 Available from: srdta.cochrane.org/
  9. Nordic Cochrane Centre, The Cochrane Collaboration Review Manager 5 (RevMan 5) 2014

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Metadata

Authors
Koliopoulos, G., Nyaga, V. N., Santesso, N., Bryant, A., Martin-Hirsch, P. P., Mustafa, R. A., Schünemann, H., Paraskevaidis, E., & Arbyn, M.
Affiliations
  • General-Maternity District Hospital Helena Venizelou (GR)
  • Institut Scientifique de Santé Publique (BE)
  • McMaster University (CA)
  • Newcastle University (GB)
  • Royal Preston Hospital, Lancashire Teaching Hospital NHS Trust; Gynaecological Oncology Unit; Sharoe Green Lane Fullwood Preston Lancashire UK PR2 9HT
  • University Hospital of Ioannina (GR)
  • Sciensano (Belgium) (BE)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2017-08-10
Volume
2018
Issue
7
Pages
CD008587-CD008587
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd008587.pub2
PMC
PMC6483676
OpenAlex
W2171104009
Cited by
494
References
145
Citations by year
2026: 25 · 2025: 71 · 2024: 82 · 2023: 61 · 2022: 70 · 2021: 72 · 2020: 52 · 2019: 40 · 2018: 16
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
European Commission (603019)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
Keywords
cervical cancer screening, HPV testing, cervical cytology, cervical intraepithelial neoplasia, CIN 2, CIN3, adenocarcinoma in situ, Hybrid Capture 2, HPV genotyping, liquid-based cytology, diagnostic accuracy, sensitivity and specificity, primary screening, test comparison, screening thresholds, bias assessment, QUADAS
MeSH terms
Adult, Aged, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Female, Humans, Middle Aged, Precancerous Conditions, Sensitivity and Specificity, Vaginal Smears, Polymerase Chain Reaction, Papillomavirus Infections, Early Detection of Cancer

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