Evidence map›Paper›PMID 38643219›Full record

ArticleClinical epigenetics2024

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

Mary Jo Fackler, Madison Pleas, Youran Li, Anushri Soni, Deyin Xing, Leslie Cope, Syed Ali, Quang Van Le, Chu Van Nguyen, Han Thi Pham and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 4 countries.

Mary Jo FacklerWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Madison PleasWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Youran LiWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Anushri SoniWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Deyin XingWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Leslie CopeWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA.
Syed AliDivision of Cytopathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Quang Van LeHanoi Medical University, National Cancer Hospital, Hanoi, Vietnam.
Chu Van NguyenDepartment of Quansu Pathology, National Cancer Hospital, Hanoi, Vietnam.
Han Thi PhamDepartment of Quansu Pathology, National Cancer Hospital, Hanoi, Vietnam.
Long Minh DuongDepartment of Quansu Pathology, National Cancer Hospital, Hanoi, Vietnam.
Eunice Vanden BergDepartment of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand/National Health Laboratory Service, Johannesburg, South Africa.
Reubina WadeeDepartment of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand/National Health Laboratory Service, Johannesburg, South Africa.
Pamela MichelowDepartment of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand/National Health Laboratory Service, Johannesburg, South Africa.
Wenlong Carl ChenNational Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa.
Maureen JoffeStrengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Christina Saetan FjeldboDepartment of Radiation Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Heidi LyngDepartment of Radiation Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Saraswati SukumarWomen's Malignancies Program, Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Rm 144, CRB1, Baltimore, MD, 21231, USA. saras@jhmi.edu.ORCID http://orcid.org/0000-0002-5656-6703
Johns Hopkins University · USNational Health Laboratory Service · ZAOslo University Hospital · NOHanoi Medical University Hospital · VNUniversity of the Witwatersrand · ZA

Funding

Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI Richard Bruce Roden · 2003 to 2026
$53.5M
Theranostic Imaging of Metastatic Prostate CancerP50CA103175 · NCI · JOHNS HOPKINS UNIVERSITY · PI BARKER, PETER B · 2003 to 2015
$17.9M
NCI Cervical Cancer Spore Program P50CA 09852NCI NIH HHS P50 CA098252NCI NIH HHS P50 CA103175The Rubenstein Family Fund 80014042
6 · The paper itself

Abstract

backgroundCervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy.

resultsMarker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers.

conclusionsThis 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Indexed as

Carcinoma, Squamous CellPapillomavirus InfectionsUterine Cervical NeoplasmsDeveloping CountriesDNA MethylationFemaleGenetic MarkersHumansPapillomaviridaeTumor Suppressor ProteinsVaginal SmearsGenetic MarkersTumor Suppressor ProteinsZNF671 protein, humanAssayCervical cancerCervical smearMarkersMethylationQM-MSPQuantitativeSensitiveSpecificTissue

Identifiers

PMID38643219
PMCPMC11032610
OpenAlexW4394987334

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.