Evidence map›Paper›PMID 29563323›Full record

ArticleScience translational medicine2018

Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.

Yuxuan Wang, Lu Li, Christopher Douville, Joshua D Cohen, Ting-Tai Yen, Isaac Kinde, Karin Sundfelt, Susanne K Kjær, Ralph H Hruban, Ie-Ming Shih and 27 more

3 registry-linked trialsAbstract read
In one paragraph

Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 145 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT02288676 recruitingnot on this map

DOvEEgene/WISE Genomics: Diagnosing Ovarian and Endometrial Cancer Early Using Genomics

TypeobservationalSponsorMcGill UniversityRan2014 to 2026Enrolled1,200ConditionsOvarian Neoplasms, Endometrial Neoplasms, Endometrial Cancer, Ovarian Cancer
NCT04258449 recruitingnot on this mapstarted 2020, after this paper: background citation

DOvEEgene Fleur: New Uterine Sampling Tool

TypeobservationalSponsorMcGill UniversityRan2020 to 2026Enrolled40ConditionsWomen With Suspected or Confirmed Gynecological DiseaseArmsDOvEEgene Fleur Sampling
NCT04812938 unknown statusnot on this mapstarted 2021, after this paper: background citation

Exploiting Pathogenic Tp53 Mutation for Early Diagnosis of Ovarian Cancer by Mean of Papanicolau Test

TypeobservationalSponsorAzienda Ospedaliera San Giovanni BattistaRan2021 to 2022Enrolled190ConditionsOvarian CancerArmsPatients with Ovarian cancer and pap test available
3 · Its place in the literature

Who cites it

145 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  8. A DNA methylation assay (MPap) using self-collected tampon versus cytology collection swab for endometrial cancer detection.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
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85 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors.

Yuxuan WangLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-2932-6042
Lu LiDivision of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-1920-4965
Christopher DouvilleLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-2510-4151
Joshua D CohenLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0003-1158-5668
Ting-Tai YenKelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0001-7399-9917
Isaac KindePapGene Inc. Baltimore, MD 21211, USA.
Karin SundfeltDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.ORCID 0000-0002-7135-3132
Susanne K KjærDepartment of Obstetrics and Gynecology, Copenhagen University Hospital Rigshospitalet, Copenhagen 2100, Denmark.ORCID 0000-0002-8347-1398
Ralph H HrubanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ie-Ming ShihDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Tian-Li WangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Robert J KurmanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Simeon SpringerLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Janine PtakLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0003-1934-8739
Maria PopoliLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Joy SchaeferLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0001-6788-8989
Natalie SillimanLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-5198-9037
Lisa DobbynLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-3159-189X
Edward J TannerKelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0003-0829-1642
Ana AngaritaKelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Maria LyckeDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.ORCID 0000-0002-1371-4649
Kirsten JochumsenDepartment of Obstetrics and Gynecology, Odense University Hospital, Odense 5000, Denmark.ORCID 0000-0002-2758-9332
Bahman AfsariDivision of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ludmila DanilovaDivision of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0003-2813-3094
Douglas A LevineDepartment of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Centre, New York University Langone Medical Center, New York, NY 10016, USA.ORCID 0000-0003-1038-8232
Kris JardonDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.ORCID 0000-0003-4042-5831
Xing ZengDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.ORCID 0000-0002-2754-7650
Jocelyne ArseneauDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.ORCID 0000-0002-4065-4792
Lili FuDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
Luis A DiazLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-7079-8914
Rachel KarchinDepartment of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID 0000-0002-5069-1239
Cristian TomasettiDivision of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0003-3277-4804
Kenneth W KinzlerLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0001-5591-1176
Bert VogelsteinLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0003-0766-3854
Amanda N FaderKelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0003-3036-0421
Lucy GilbertDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, Oncology, and Pathology, McGill University and McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0001-8605-5472
Nickolas PapadopoulosLudwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. lucy.gilbert@mcgill.ca afader1@jhmi.edu ctomasetti@jhu.edu kinzlke@jhmi.edu vogelbe@jhmi.edu npapado1@jhmi.edu.ORCID 0000-0001-7135-7451

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
Development of in vitro diagnostic multivariate index assay using liquid-based cervical cytology specimen and/or serum/plasma biomarkers for the detection of early stage or low-volume ovarian cancerU01CA200469 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHIH, IE-MING, ZHANG, ZHEN · 2016 to 2021
$2.9M
Informatics Tools for High-throughput Analysis of Cancer MutationsU24CA204817 · NCI · JOHNS HOPKINS UNIVERSITY · PI KARCHIN, RACHEL · 2016 to 2020
$2.5M
Experimental Therapeutics by targeting Spleen Tyrosine KinaseR01CA215483 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHIH, IE-MING · 2017 to 2021
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA006973NCI NIH HHS R01 CA215483NCI NIH HHS U01 CA200469NCI NIH HHS U24 CA204817NIGMS NIH HHS T32 GM007309
6 · The paper itself

Abstract

We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease. In contrast, only 1.4% of 714 women without cancer had positive Pap brush samples (specificity, ~99%). Next, we showed that intrauterine sampling with a Tao brush increased the detection of malignancy over endocervical sampling with a Pap brush: 93% of 123 (95% CI, 87 to 97%) patients with endometrial cancer and 45% of 51 (95% CI, 31 to 60%) patients with ovarian cancer were positive, whereas none of the samples from 125 women without cancer were positive (specificity, 100%). Finally, in 83 ovarian cancer patients in whom plasma was available, circulating tumor DNA was found in 43% of patients (95% CI, 33 to 55%). When plasma and Pap brush samples were both tested, the sensitivity for ovarian cancer increased to 63% (95% CI, 51 to 73%). These results demonstrate the potential of mutation-based diagnostics to detect gynecologic cancers at a stage when they are more likely to be curable.

Indexed as

AdolescentAdultAgedEndometrial NeoplasmsFemaleHumansLiquid BiopsyMiddle AgedOvarian NeoplasmsPapanicolaou TestRetrospective StudiesVaginal SmearsYoung Adult

Identifiers

PMID29563323
PMCPMC6320220

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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.