{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:31:06Z","timestamp":1791289866763,"version":"4.3.0"},"reference-count":41,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2012,12,13]]},"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human epididymis protein 4 (HE4) measurements in serum have been proposed for improving the specificity of laboratory identification of ovarian cancer (OC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To critically revise the available literature on the comparison between the diagnostic accuracy of HE4 and carbohydrate antigen 125 (CA-125) to confirm the additional clinical value of HE4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A literature search was undertaken on electronic databases and references from retrieved articles; articles were analysed according to predefined criteria. Meta-analyses for HE4 and CA-125 biomarkers with OR, diagnostic sensitivity, specificity, positive (LR+) and negative (LR\u2013) likelihood ratios as effect sizes were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>16 articles were originally included in meta-analyses, but two for HE4 and one for CA-125 were eliminated as outliers. Furthermore, for HE4 a publication bias was detected. ORs for both HE4 (37.2, 95% CI 19.0 to 72.7, adjusted for publication bias) and CA-125 (15.4, 95% CI 10.4 to 22.8) were significant, although in a heterogeneous set of studies (p&lt;0.0001). By combining sensitivity and specificity, the overall LR+ and LR\u2013 were 13.0 (95% CI 8.2 to 20.7) and 0.23 (95% CI 0.19 to 0.28) for HE4 and 4.2 (95% CI 3.1 to 5.6) and 0.27 (95% CI 0.23 to 0.31) for CA-125, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HE4 measurement seems to be superior to CA-125 in terms of diagnostic performance for identification of OC in women with suspected gynaecological disease. Due to the high prevalence of OC in post-menopausal women and the need for data focused on early tumour stages, more studies tailored on these specific subsets are needed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2012-201031","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T22:39:12Z","timestamp":1361399952000},"page":"273-281","source":"Crossref","is-referenced-by-count":162,"title":["Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review"],"prefix":"10.1136","volume":"66","author":[{"given":"Simona","family":"Ferraro","sequence":"first","affiliation":[{"name":"Laboratorio Analisi Chimico-Cliniche, Azienda Ospedaliera \u2018Luigi Sacco\u2019, and Cattedra di Biochimica Clinica e Biologia Molecolare Clinica, Universit\u00e0 degli Studi, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Braga","sequence":"additional","affiliation":[{"name":"Laboratorio Analisi Chimico-Cliniche, Azienda Ospedaliera \u2018Luigi Sacco\u2019, and Cattedra di Biochimica Clinica e Biologia Molecolare Clinica, Universit\u00e0 degli Studi, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lanzoni","sequence":"additional","affiliation":[{"name":"Sezione di Statistica Medica e Biometria, Universit\u00e0 degli Studi, Milano, Italy"},{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Boracchi","sequence":"additional","affiliation":[{"name":"Sezione di Statistica Medica e Biometria, Universit\u00e0 degli Studi, Milano, Italy"},{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia Mario","family":"Biganzoli","sequence":"additional","affiliation":[{"name":"Sezione di Statistica Medica e Biometria, Universit\u00e0 degli Studi, Milano, Italy"},{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Panteghini","sequence":"additional","affiliation":[{"name":"Laboratorio Analisi Chimico-Cliniche, Azienda Ospedaliera \u2018Luigi Sacco\u2019, and Cattedra di Biochimica Clinica e Biologia Molecolare Clinica, Universit\u00e0 degli Studi, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2013,2,20]]},"reference":[{"key":"2025092503405308000_66.4.273.1","unstructured":"Ferlay J Shin HR Bray F . 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