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

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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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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: Nyaga, Victoria N
Santesso, Nancy
Bryant, Andrew
Mustafa, Reem A
Schünemann, Holger
Paraskevaidis, Evangelos
Arbyn, Marc
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: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
onlinelibrary.wiley.com/termsAndConditions (vor)
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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Cytology versus HPV testing for cervical cancer screening in the general population

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