The Diagnostic Accuracy of Serum and Urine Human Epididymis Protein 4 (HE4) in Ovarian Cancer in 15,394 Subjects: An Updated Meta-Analysis

Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent r...

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Published in:	Curēus (Palo Alto, CA) Vol. 14; no. 10; p. e30457
Main Authors:	Nalini, Neelam, Kumar, Amit, Sharma, Saumya, Singh, Bijeta, Singh, Aditya V, Prakash, Jay, Singh, Shreshtha
Format:	Journal Article
Language:	English
Published:	United States Cureus Inc 19-10-2022 Cureus
Subjects:	Accuracy Biopsy Cervical cancer Epidemiology/Public Health Ethnicity Immunoassay Medical diagnosis Meta-analysis Mortality Obstetrics/Gynecology Oncology Ovarian cancer Urine Womens health Belgium United States > US China Egypt Poland Italy Thailand India carbohydrate antigen 125 biomarker ovarian cancer he4 transvaginal sonography
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Abstract	Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947.
AbstractList	Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947.Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947. Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947. Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947. BackgroundWe aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer.MethodsElectronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library.Result and conclusionThis meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer.Registration numberThis meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947.
Author	Singh, Aditya V Sharma, Saumya Nalini, Neelam Singh, Bijeta Singh, Shreshtha Kumar, Amit Prakash, Jay
AuthorAffiliation	6 Anaesthesia, John Hunter Hospital, New South Wales, AUS 1 Obstetrics and Gynaecology, Rajendra Institute of Medical Sciences, Ranchi, IND 5 Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, IND 3 Obstetrics and Gynaecology, Medinirai Medical College, Ranchi, IND 2 Laboratory Medicine, Rajendra institute of Medical Sciences, Ranchi, IND 4 Medicine, Laxmi Chandravanshi Medical College, Ranchi, IND
AuthorAffiliation_xml	– name: 4 Medicine, Laxmi Chandravanshi Medical College, Ranchi, IND – name: 1 Obstetrics and Gynaecology, Rajendra Institute of Medical Sciences, Ranchi, IND – name: 5 Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, IND – name: 2 Laboratory Medicine, Rajendra institute of Medical Sciences, Ranchi, IND – name: 3 Obstetrics and Gynaecology, Medinirai Medical College, Ranchi, IND – name: 6 Anaesthesia, John Hunter Hospital, New South Wales, AUS
Author_xml	– sequence: 1 givenname: Neelam surname: Nalini fullname: Nalini, Neelam organization: Obstetrics and Gynaecology, Rajendra Institute of Medical Sciences, Ranchi, IND – sequence: 2 givenname: Amit surname: Kumar fullname: Kumar, Amit organization: Laboratory Medicine, Rajendra institute of Medical Sciences, Ranchi, IND – sequence: 3 givenname: Saumya surname: Sharma fullname: Sharma, Saumya organization: Obstetrics and Gynaecology, Rajendra Institute of Medical Sciences, Ranchi, IND – sequence: 4 givenname: Bijeta surname: Singh fullname: Singh, Bijeta organization: Obstetrics and Gynaecology, Medinirai Medical College, Ranchi, IND – sequence: 5 givenname: Aditya V surname: Singh fullname: Singh, Aditya V organization: Medicine, Laxmi Chandravanshi Medical College, Ranchi, IND – sequence: 6 givenname: Jay surname: Prakash fullname: Prakash, Jay organization: Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, IND – sequence: 7 givenname: Shreshtha surname: Singh fullname: Singh, Shreshtha organization: Anaesthesia, John Hunter Hospital, New South Wales, AUS
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Keywords	carbohydrate antigen 125 biomarker ovarian cancer he4 transvaginal sonography
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Snippet	Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods... BackgroundWe aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian... Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods...
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SubjectTerms	Accuracy Biopsy Cervical cancer Epidemiology/Public Health Ethnicity Immunoassay Medical diagnosis Meta-analysis Mortality Obstetrics/Gynecology Oncology Ovarian cancer Urine Womens health
Title	The Diagnostic Accuracy of Serum and Urine Human Epididymis Protein 4 (HE4) in Ovarian Cancer in 15,394 Subjects: An Updated Meta-Analysis
URI	https://www.ncbi.nlm.nih.gov/pubmed/36415437 https://www.proquest.com/docview/2742923163 https://www.proquest.com/docview/2739430892 https://pubmed.ncbi.nlm.nih.gov/PMC9677808
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