{rfName}
Mu

Indexed in

License and use

Icono OpenAccess

Citations

58

Altmetrics

Grant support

The analysis is part of PROMISE, which was funded through Cancer Research UK PRC Programme Grant A12677 and by The Eve Appeal. University College London investigators received support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre and from MRC core funding (MR_UU_12023). UKCTOCS was core funded by the Medical Research Council (G9901012 and G0801228), Cancer Research UK (C1479/A2884), and the Department of Health with additional support from the Eve Appeal. J.F.T. received support from CRUK Early Detection Committee Project Award (C12077/A26223). S.J.S. received additional support from an NCI Early Detection Research Network grant (CA152990). R.C.B.J. was supported by funds from the Early Detection Research Network (5 U01 CA200462-02) and the MD Anderson Ovarian SPOREs (P50 CA83639 and P50 CA217685), National Cancer Institute, Department of Health and Human Services, the Cancer Prevention Research Institute of Texas (RP101382 and RP160145), Golfer's Against Cancer, the Mossy Foundation, the Roberson Endowment, National Foundation for Cancer Research, The K Yao Foundation, UT MD Anderson Women's Moon Shot and generous donations from Stuart and Gaye Lynn Zarrow. A.Z. acknowledges support by MRC grant MR/R02524X/1 and the grant of the Ministry of Education and Science of the Russian Federation Agreement No. 074-02-2018-330.

Analysis of institutional authors

Marino, IpAuthor

Share

September 27, 2022
Publications
>
Article
Sí

Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women

Publicated to:Cancers. 12 (7): E1931-12 - 2020-07-01 12(7), DOI: 10.3390/cancers12071931

Authors: Gentry-Maharaj, Aleksandra; Blyuss, Oleg; Ryan, Andy; Burnell, Matthew; Karpinskyj, Chloe; Gunu, Richard; Kalsi, Jatinderpal K; Dawnay, Anne; Marino, Ines P; Manchanda, Ranjit; Lu, Karen; Yang, Wei-Lei; Timms, John F; Parmar, Max; Skates, Steven J; Bast, Robert C, Jr; Jacobs, Ian J; Zaikin, Alexey; Menon, Usha

Affiliations

Barts Hlth NHS Trust, Clin Biochem, London EL 8PR, England - Author
Barts Hlth NHS Trust, St Bartholomews Hosp, Dept Gynaecol Oncol, London EC1A 7BE, England - Author
Harvard Med Sch, Boston, MA 02114 USA - Author
Lobachevsky Univ Nyzhniy Novgorod, Dept Appl Math, Nizhnii Novgorod 603105, Russia - Author
Massachusetts Gen Hosp, Boston, MA 02114 USA - Author
Queen Mary Univ London, Barts CRUK Canc Ctr, Wolfson Inst Prevent Med, London EC1M 6BQ, England - Author
Sechenov First Moscow State Med Univ, Dept Paediat & Paediat Infect Dis, Moscow 119991, Russia - Author
UCL, Dept Math, London WC1H 0AY, England - Author
UCL, Inst Womens Hlth, Dept Womens Canc, London WC1E 6BT, England - Author
UCL, MRC Clin Trials Unit, Inst Clin Trials & Methodol, London WC1V 6LJ, England - Author
Univ Hertfordshire, Sch Phys Astron & Math, Hatfield AL10 9AB, Herts, England - Author
Univ New South Wales, Sydney, NSW 2052, Australia - Author
Univ Rey Juan Carlos, Dept Biol & Geol Phys & Inorgan Chem, Madrid 28933, Spain - Author
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA - Author
See more

Abstract

Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2-5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871-0.952) and 90.5% (82.5-98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women.

Keywords

AdultAlgorithmAntigen detectionArticleBiomarkersBlood samplingCa 125 antigenCa 72-4 antigenCa125Cancer screeningCase control studyCollaborative trialControlled studyDiagnostic valueFemaleHe4HumanLongitudinal studyLungMajor clinical studyMmtMortalityOvarian cancerOvary cancerPerformancePointPopulation researchPostmenopausal womenPostmenopauseProstateProtein analysisProtein antibodyProtein blood levelProtein p53 autoantibodyRiskScreeningSensitivitySensitivity analysisTimeTuboovarian cancerTumor invasionUkctocsUnclassified drugUnited kingdomUterine tube tumorValidation processWap four-disulfide core domain protein 2

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 51/242, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 6.85, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-10, the following number of citations:

  • WoS: 20
  • Scopus: 22
  • Europe PMC: 14

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-10:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 31.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 33 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 5.3.
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Australia; Russia; United Kingdom; United States of America.