ArticleJournal of the National Cancer Institute2021
p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06366516 (Clinical Validation of ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671 Methylation in HPV Positive Women), which is not on this map. Cited by 44 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Clinical Validation of ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671 Methylation in HPV Positive Women: a Multi-center RCT From China
Who cites it
44 citing papers in PubMed, 4 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- A bibliometric analysis and visualization of trends in cervical cancer screening technologies based on dual-database analysis.Frontiers in oncology · 2026Pooled it
- Italian guidelines for cervical cancer screening. Multisocietal recommendations on the use of biomarkers in HPV screening with risk-based approach and GRADE methodology.British journal of cancer · 2025Guideline
- Pooled it
- Canadian Guideline on the Management of a Positive Human Papillomavirus Test and Guidance for Specific Populations.Current oncology (Toronto, Ont.) · 2023Guideline
- Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study.Microbiology spectrum · 2025Trial
- Role and insights of human papillomavirus E5 oncoprotein in cervical carcinogenesis.Experimental and therapeutic medicine · 2026Article
- HPV integration as a triage tool for HPV-positive women in cervical cancer screening.Tumour virus research · 2026Article
- Development of a Double-Antibody Sandwich ELISA for the Detection of HPV16 E6 Protein.Diagnostics (Basel, Switzerland) · 2026Article
- HPV status determines prognostic gene expression methylation and immune infiltration in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- A nomogram-based prediction model for assessing the risk of vain and stump cancer recurrence following radical surgery for cervical cancer.Discover oncology · 2026Article
- Advances in Screening, Immunotherapy, Targeted Agents, and Precision Surgery in Cervical Cancer: A Comprehensive Clinical Review (2018-2025).Current oncology (Toronto, Ont.) · 2026Review
- A prospective observational study on the value of HPV E6/E7 oncoprotein immunocytochemistry for triaging HPV-positive women.Frontiers in medicine · 2026Article
- Comparison of ThinPrep cytology and high-risk human papillomavirus testing with different triage protocols for cervical cancer screening.American journal of translational research · 2026Article
- Comparative Diagnostic Performance of DNA Ploidy Analysis and p16/Ki67 Dual-Staining with Cytology in hrHPV-Defined Subgroups: A Single-Center Evaluation.Cancer management and research · 2026Article
- Comparative performance of standalone E6/E7 mRNA testing versus a combined DNA genotyping and viral load assay for detecting cervical high-grade lesions: a retrospective paired study.American journal of translational research · 2026Article
- Real-world efficacy, safety, and associated biomarkers of cadonilimab in cervical cancer: a prospective observational study.Frontiers in immunology · 2026Observational
- Clinical performance of triage strategies for HPV-positive women in cervical cancer screening in rural Yunnan China.BMC cancer · 2025Article
- Identification of the important role of CA9 in immune infiltration and prognosis in cervical cancer.Future science OA · 2025Article
- Impact of differentiating between persistent and new infections on colposcopy referral in HPV-positive triage-negative women: results from the NTCC2 study.Infectious agents and cancer · 2025Article
- Molecular Insights into HPV-Driven Head and Neck Cancers: From Viral Oncoproteins to Precision Therapeutics.Viruses · 2025Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundThe study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis.
methodsWomen aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided.
results40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both).
conclusionsp16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.
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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.