The performance of HE4 alone and in combination with CA125 for the detection of ovarian cancer in an enriched primary care population

Chloe E. Barr; Garth Funston; David Jeevan; Sudha Sundar; Luke T.A. Mounce; Emma J. Crosbie

doi:10.3390/cancers14092124

The performance of HE4 alone and in combination with CA125 for the detection of ovarian cancer in an enriched primary care population

Chloe E. Barr, Garth Funston, David Jeevan, Sudha Sundar, Luke T.A. Mounce, Emma J. Crosbie^*

^*Corresponding author for this work

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Abstract

Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (</>51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94–0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5–100.0), specificity: 80.1% (95%CI 76.7–83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1–92.2), specificity: 87.2% (95%CI 84.1–90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.

Original language	English
Article number	2124
Number of pages	18
Journal	Cancers
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/cancers14092124
Publication status	Published - 24 Apr 2022

Bibliographical note

Funding Information:
LumipulseG HE4 immunoassay kits were generously donated by Fujirebio for use in this research. Fujirebio played no other role in the conduct of this study, analysis of the data or the decision to publish. C.E.B. was supported through an MFT Clinical Research Fellowship, and E.J.C. was supported through the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). This work was supported by Wellbeing of Women (Award Reference ELS701) (GF, EJC). D.J. was supported by Wellbeing of Women (Award Reference RTF707). This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of Fujirebio, the NHS, NIHR, or the Department of Health.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

biomarker
CA125
early detection
HE4
ovarian cancer
primary care
ROMA

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14092124Licence: Creative Commons: Attribution (CC BY)

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Cite this

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title = "The performance of HE4 alone and in combination with CA125 for the detection of ovarian cancer in an enriched primary care population",

abstract = "Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94–0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5–100.0), specificity: 80.1% (95%CI 76.7–83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1–92.2), specificity: 87.2% (95%CI 84.1–90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.",

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note = "Funding Information: LumipulseG HE4 immunoassay kits were generously donated by Fujirebio for use in this research. Fujirebio played no other role in the conduct of this study, analysis of the data or the decision to publish. C.E.B. was supported through an MFT Clinical Research Fellowship, and E.J.C. was supported through the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). This work was supported by Wellbeing of Women (Award Reference ELS701) (GF, EJC). D.J. was supported by Wellbeing of Women (Award Reference RTF707). This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of Fujirebio, the NHS, NIHR, or the Department of Health. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Sundar, Sudha

AU - Mounce, Luke T.A.

AU - Crosbie, Emma J.

N1 - Funding Information: LumipulseG HE4 immunoassay kits were generously donated by Fujirebio for use in this research. Fujirebio played no other role in the conduct of this study, analysis of the data or the decision to publish. C.E.B. was supported through an MFT Clinical Research Fellowship, and E.J.C. was supported through the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). This work was supported by Wellbeing of Women (Award Reference ELS701) (GF, EJC). D.J. was supported by Wellbeing of Women (Award Reference RTF707). This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of Fujirebio, the NHS, NIHR, or the Department of Health. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94–0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5–100.0), specificity: 80.1% (95%CI 76.7–83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1–92.2), specificity: 87.2% (95%CI 84.1–90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.

AB - Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94–0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5–100.0), specificity: 80.1% (95%CI 76.7–83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1–92.2), specificity: 87.2% (95%CI 84.1–90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.

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The performance of HE4 alone and in combination with CA125 for the detection of ovarian cancer in an enriched primary care population

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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