ArticlePloS one2014
HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed.
- Silencing HPV: the rise of RNA therapeutics in cervical cancer.Infectious agents and cancer · 2026Review
- Optimization of RNAscope for HPV mRNA detection in liquid-based cervical cytology samples.Frontiers in oncology · 2026Article
- Immune Dysregulation and Viral Persistence in HPV-HIV Coinfection: Oncogenic and Clinical Implications.HIV/AIDS (Auckland, N.Z.) · 2026Review
- Comparative Analysis Reveals Recurrent Molecular Alterations in Low-Risk Human Papillomavirus 6 and Human Papillomavirus 11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Primary lung adenocarcinoma harboring upper mediastinal lymphatic skip metastasis of cervical squamous cell carcinoma: A case report and literature review.Oncology letters · 2024Article
- Histopathological and Virological Findings of a Penile Papilloma in a Japanese Stallion with Equus Caballus Papillomavirus 2 (EcPV2).Pathogens (Basel, Switzerland) · 2024Article
- Visualization of Individual RNA Molecules by Proximity Ligation-Based Chromogenic In Situ Hybridization Assay.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Human papillomavirus-related neoplasia of the ocular adnexa.Acta ophthalmologica · 2022Article
- Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment.Virology journal · 2022Article
- Localization and genotyping of canine papillomavirus in canine inverted papillomas.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2021Article
- Establishment of a Three-Dimensional In Vitro Model of Equine Papillomavirus Type 2 Infection.Viruses · 2021Article
- Accuracy of HPV E6/E7 mRNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions.Diagnostic pathology · 2021Article
- MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.PLoS pathogens · 2021Article
- Correlation between Human Papillomavirus Codetection Profiles and Cervical Intraepithelial Neoplasia in Japanese Women.Microorganisms · 2020Article
- Genomic Characterization of HPV-related and Gastric-type Endocervical Adenocarcinoma: Correlation With Subtype and Clinical Behavior.International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2020Article
- Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization.Journal of pathology and translational medicine · 2020Article
- Clinicopathologic Association and Prognostic Value of MELF Pattern in Invasive Endocervical Adenocarcinoma (ECA) as Classified by IECC.International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2020Article
- Analysis of factors affecting the prognosis of patients with cervical intraepithelial neoplasia 2.Oncology letters · 2020Article
- Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.BMC veterinary research · 2019Article
- Accuracy of mRNA HPV Tests for Triage of Precursor Lesions and Cervical Cancer: A Systematic Review and Meta-Analysis.Journal of oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when 'LSIL vs. HSIL' assignment is equivocal.
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.