Cited by 851Cervical Cancer and HPV ResearchWomen's cancer prevention and managementReproductive tract infections research

The DOI matches its Crossref record; 130 of the 130 references it cites were found in a registry or an index; 14 of the 33 sources its claims cite were checked for support.

Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses

Open access

Abstract

Objective: To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women. Design: Updated meta-analysis. Data sources: Medline (PubMed), Embase, and CENTRAL from 1 January 2013 to 15 April 2018 (accuracy review), and 1 January 2014 to 15 April 2018 (participation review). Review methods: Accuracy review: hrHPV assay on a vaginal self sample and a clinician sample; and verification of the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by colposcopy and biopsy in all enrolled women or in women with positive tests. Participation review: study population included women who were irregularly or never screened; women in the self sampling arm (intervention arm) were invited to collect a self sample for hrHPV testing; women in the control arm were invited or reminded to undergo a screening test on a clinician sample; participation in both arms was documented; and a population minimum of 400 women. Results: 56 accuracy studies and 25 participation trials were included. hrHPV assays based on polymerase chain reaction were as sensitive on self samples as on clinician samples to detect CIN2+ or CIN3+ (pooled ratio 0.99, 95% confidence interval 0.97 to 1.02). However, hrHPV assays based on signal amplification were less sensitive on self samples (pooled ratio 0.85, 95% confidence interval 0.80 to 0.89). The specificity to exclude CIN2+ was 2% or 4% lower on self samples than on clinician samples, for hrHPV assays based on polymerase chain reaction or signal amplification, respectively. Mailing self sample kits to the woman’s home address generated higher response rates to have a sample taken by a clinician than invitation or reminder letters (pooled relative participation in intention-to-treat-analysis of 2.33, 95% confidence interval 1.86 to 2.91). Opt-in strategies where women had to request a self sampling kit were generally not more effective than invitation letters (relative participation of 1.22, 95% confidence interval 0.93 to 1.61). Direct offer of self sampling devices to women in communities that were underscreened generated high participation rates (>75%). Substantial interstudy heterogeneity was noted (I 2 >95%). Conclusions: When used with hrHPV assays based on polymerase chain reaction, testing on self samples was similarly accurate as on clinician samples. Offering self sampling kits generally is more effective in reaching underscreened women than sending invitations. However, since response rates are highly variable among settings, pilots should be set up before regional or national roll out of self sampling strategies.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In updated meta-analyses of 56 diagnostic accuracy studies and 25 randomized participation trials, hrHPV testing on self samples was as sensitive as clinician samples when using PCR-based assays, but less sensitive with signal-amplification assays. Mailing self-sampling kits increased participation among underscreened women, though effects varied substantially by invitation strategy and setting.

Key findings

  • PCR-based hrHPV assays on self samples were as sensitive as clinician samples for CIN2+ (pooled ratio 0.99, 95% CI 0.97 to 1.02) and CIN3+ (0.99, 0.96 to 1.02), with slightly lower specificity to exclude CIN2+ (0.98, 0.97 to 0.99).
  • Signal-amplification hrHPV assays were less sensitive on self samples for CIN2+ (0.85, 0.80 to 0.89) and CIN3+ (0.86, 0.76 to 0.98), and less specific to exclude CIN2+ (0.96, 0.93 to 0.98).
  • In intention-to-treat analysis, mailing self-sampling kits to the home increased participation versus invitation/reminder letters (relative participation 2.33, 95% CI 1.86 to 2.91), whereas opt-in strategies were not significantly more effective (1.22, 0.93 to 1.61).
  • Door-to-door delivery generated high participation (>75%; pooled self-sampling participation 94.2% per protocol and 94.6% intention-to-treat), and CIN2+ detection per 1000 invited women was higher in self-sampling arms (relative proportion 2.28, 95% CI 1.44 to 3.61).

Methods

  • Updated meta-analyses: accuracy review searched Medline, Embase, and CENTRAL from 1 January 2013 to 15 April 2018; participation review searched from 1 January 2014 to 15 April 2018.
  • Included 56 diagnostic test accuracy studies comparing hrHPV testing on vaginal self samples versus clinician samples with CIN2+/CIN3+ verification, and 25 randomized trials of self-sampling offers among irregularly/never-screened women with at least 400 women.
  • Pooled accuracy using a bivariate normal model for logit-transformed sensitivity/specificity; pooled participation using random-effects models for proportions and ratios; assessed quality with QUADAS-2 and Cochrane risk-of-bias tools.

Limitations

  • Stated: meta-analyses based on aggregated published results lacked detailed data equally stratified by potentially influencing factors; meta-regression including only eight studies did not reveal age effects, and subgroup analyses/meta-regressions were not possible because covariates were categorized differently across studies.
  • Stated: the authors propose pooling individual patient data from the best trials to evaluate influential factors more efficiently.
  • Evident: substantial interstudy heterogeneity was noted (I²>95%), including high heterogeneity for participation outcomes and opt-in results (P<0.001), and quality reporting was incomplete for some domains, such as uninterpretable results poorly reported for evaluated tests (39%) and reference standard (45%).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.k4823

Cites

130 of 130 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

14 of 33 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

Show all 60 claims

  • Probably not a substantial claim. 9
  • It may state two separate claims as one. 19
  • The quote only partly states this claim. 2
25 of 25
  • The paper relies on this without support.

    Intention-to-treat analyses of participation trials reflect the overall public health effect in a real world situation.

    “In the intention-to-treat analyses, which reflected the overall public health effect in a real world situation, we additionally included women in the experimental arm who had been offered self sampling but choose to have a clinician sample taken instead.”
  • The paper relies on this without support.

    New assays, self sampling devices, storage media, and participation strategies have entered the market since the publication of the two previous meta-analyses, and more accuracy and participation studies have been conducted.

    “New assays, self sampling devices, storage media, and participation strategies have entered the market since the publication of these two meta-analyses; and more accuracy and participation studies have been conducted.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Vaginal-lavage study count differs between text and table

    Minor

    The text gives a count of two for polymerase-chain-reaction testing on vaginal lavage self samples, but table 2 lists four studies for that category.

1 of 1

Citations

Cites

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Show all 130 references

Research works printed but not linked: 2

  1. IARC, 2005, Cervix Cancer Screening. IARC Handbooks of Cancer Prevention. Vol. 10
  2. Deeks, 2013, Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 1.0.0.

Cited by

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Metadata

Authors
Arbyn, M., Smith, S. B., Temin, S., Sultana, F., & Castle, P.
Affiliations
  • Sciensano (Belgium) (BE)
  • American Society of Clinical Oncology (US)
  • The University of Melbourne (AU)
  • Albert Einstein College of Medicine (US)
Corresponding author
Arbyn, Marc
Venue
BMJ
Publisher
BMJ
Published
2018-12-05
Volume
363
Pages
k4823
ISSN
  • 1756-1833 (ISSN-L)
  • 0959-8138
OpenAlex
W2902810541
Cited by
851
References
130
Citations by year
2026: 93 · 2025: 136 · 2024: 136 · 2023: 137 · 2022: 116 · 2021: 104 · 2020: 89 · 2019: 39
FWCI
39.55
Type
journal article
Language
en
Open access
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, other-oa)
  • PubMed Central (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
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, self-sampling, cervical intraepithelial neoplasia, CIN2+ detection, diagnostic accuracy, underscreened women, screening uptake, reminder letters, clinician-collected samples, community-based screening
MeSH terms
Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Colposcopy, Female, Humans, Mass Screening, Sensitivity and Specificity, Specimen Handling, Vagina, Vaginal Smears, Incidence, Randomized Controlled Trials as Topic, Papillomaviridae, Papillomavirus Infections, Early Detection of Cancer, Intention to Treat Analysis

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