SynthesisCancer treatment reviews2009
p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis.
Synthesis in Cancer treatment reviews, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02522585 (Predictive Value of p16 and Ki-67 Immunohistochemical Staining and NK Cells in Expectant Management of Cervical Intraepithelial Neoplasia Grade 2), which is not on this map. Cited by 94 papers, 8 of them syntheses that pooled 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.
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.
Predictive Value of p16 and Ki-67 Immunohistochemical Staining and NK Cells in Expectant Management of Cervical Intraepithelial Neoplasia Grade 2
Who cites it
94 citing papers in PubMed, 8 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- Pooled it
- p16 immunostaining in histological grading of anal squamous intraepithelial lesions: a systematic review and meta-analysis.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Pooled it
- Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis.BMJ (Clinical research ed.) · 2018Pooled it
- Immediate referral to colposcopy versus cytological surveillance for minor cervical cytological abnormalities in the absence of HPV test.The Cochrane database of systematic reviews · 2017Pooled it
- Prognostic significance of overexpressed p16INK4a in patients with cervical cancer: a meta-analysis.PloS one · 2014Pooled it
- p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities: a systematic review and meta-analysis.Cancer cytopathology · 2012Pooled it
- Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate.Journal of cellular and molecular medicine · 2009Pooled it
- The Diagnostic Value of p16/Ki67 Dual Immunostaining for Anal Intraepithelial Neoplasia: A Meta-Analysis.American journal of men's healthPooled it
- Trial
- Automated detection of dual p16/Ki67 nuclear immunoreactivity in liquid-based Pap tests for improved cervical cancer risk stratification.Annals of biomedical engineering · 2012Trial
- A novel HPV E6/E7-regulated long noncoding RNA CRL suppresses cervical intraepithelial neoplasia progression by attenuating ferroptosis.Human cell · 2026Article
- Article
- The likely possibility of predicting treatment outcomes of cervical lesions using serum FOXP3 and P16INK4A as shown by a cohort study in South Western Uganda.Discover oncology · 2026Article
- Article
- Non-invasive diagnosis of vulvar dysplasia using cervical methylation markers-a case control study.BMC medicine · 2025Article
- Article
- Diagnostic Accuracy of Serum P16ink4A and FOX-P3 Concentrations for Detection of Cervical Lesions Among Women Attending a Cervical Cancer Clinic in Western Uganda: A Case-Control Study.Analytical cellular pathology (Amsterdam) · 2025Article
- Looking Back, Moving Forward: Challenges and Opportunities for Global Cervical Cancer Prevention and Control.Viruses · 2024Review
- Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion.Diagnostic pathology · 2024Article
- High-Risk HPV CISH Detection in Cervical Biopsies with Weak and/or Focal p16 Immunohistochemical Positivity.International journal of molecular sciences · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundP16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment. MATERIAL AND
methodsWe conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion.
resultsSixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%).
conclusionAlthough there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.