{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:04:55Z","timestamp":1789671895159,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Oncology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Cancerfonden 23 3074 Pj 01 H"],"award-info":[{"award-number":["Cancerfonden 23 3074 Pj 01 H"]}],"id":[{"id":"https:\/\/ror.org\/0527jb766","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Two randomized trials have shown that screening with CA-125 is not of value for reducing ovarian cancer mortality. This appears to be because changes in CA-125 occur too late in the disease process to allow for surgical cure of early-stage disease.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine whether glycovariants of CA-125 could detect ovarian cancer years before clinical diagnosis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Case-control study of cryopreserved blood samples and data from the population-based Malm\u00f6 Diet and Cancer cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Population-based study in Sweden.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Serum was available for 17,297 women aged 44 \u2013 73 collected at baseline in 1991-1996 and from 2,168 women re-sampled in 2007-2012. Participants\u2019 records were linked to the Swedish cancer registry to identify 82 women with incident ovarian cancer diagnosed up to 10 years after blood draw. Cases were matched 1:3 with controls by age and venipuncture date.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Exposure<\/jats:title>\n                  <jats:p>\n                    Serum was measured for CA-125 glycovariants Sialyl-Thomsen-nouveau (STn) and Macrophage-Galactose-Lectin (MGL) using GLYVAR\n                    <jats:sup>\u00ae<\/jats:sup>\n                    Ovarian I and II assays (Uniogen), conventional CA-125 (CanAg CA125 EIA, Fujirebio) and HE4 EIA (Fujirebio).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main outcome measure<\/jats:title>\n                  <jats:p>Ovarian cancer.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The CA-125-STn was associated with subsequent ovarian cancer (p=0.002). In the primary analysis restricted to cases within 5 years, the area-under-the-curve for CA-125-STn was 0.68; with moving window analysis suggesting retained predictiveness up to 5-7 years. Of the cases diagnosed within 5 years, 27% were in the top 5% of CA-125-STn levels (\u22652.3 U\/ml), with 35% and 49% of cases diagnosed in the top 10% and 20% respectively. Our findings were replicated by independent measurements of a separate aliquot from a subset of cases and controls. Neither CA-125, HE4 nor CA-125 glycovariants detected by MGL importantly predicted subsequent ovarian cancer.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>CA-125-STn can detect ovarian cancer several years before clinical diagnosis. Further research is warranted on larger cohorts with sequential samples to determine the shape of the relationship between CA-125-STn and risk, the value of longitudinal sampling of CA-125-STn, and whether other markers could be combined with CA-125-STn to more accurately predict ovarian cancer risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Question<\/jats:title>\n                    <jats:p>Can glycovariants of CA-125 detect ovarian cancer years before clinical diagnosis?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>In a case-control study of 323 Swedish women followed longitudinally, the Sialyl-Thomsen-nouveau (STn) glycovariant of CA-125, but not conventional CA-125 or other markers, predicted ovarian cancer. Close to half of ovarian cancer cases within 5 years of blood sample occurred in the patients with the top 20% of CA-125-STn glycovariant levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Meaning<\/jats:title>\n                    <jats:p>CA-125-STn can detect ovarian cancer several years before clinical diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.11.26362728","type":"posted-content","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:25:15Z","timestamp":1789449915000},"source":"Crossref","is-referenced-by-count":0,"title":["Glycovariants of CA-125 in the early detection of ovarian cancer"],"prefix":"10.64898","author":[{"given":"Andrew J.","family":"Vickers","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center New York, NY, 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