Evaluation of CA-125, HE4, ROMA, and Copenhagen Index for Preoperative Risk Stratification of Adnexal Masses in Indian Women: A Prospective Cross-Sectional Study

Evaluation of CA-125, HE4, ROMA, and Copenhagen Index for Preoperative Risk Stratification of Adnexal Masses in Indian Women: A Prospective Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of CA-125, HE4, ROMA, and Copenhagen Index for Preoperative Risk Stratification of Adnexal Masses in Indian Women: A Prospective Cross-Sectional Study Nilanchali Singh¹, Chetanya Mittal¹, Aaroshi Gupta¹, Ishika Gupta¹, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-10002273/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Introduction Ovarian cancer causes ~ 207,000 deaths annually worldwide (GLOBOCAN 2022), with India bearing ~ 16% of the global burden. Despite screening advances, biomarkers remain essential for triage in low-resource settings. This study assessed CA-125, HE4, Risk of Ovarian Malignancy Algorithm (ROMA), and Copenhagen Index (CPH-I) for distinguishing benign from malignant adnexal masses in Indian women. Methodology: The study is a single-center, cross-sectional study enrolling participants prospectively conducted at a tertiary center. Serum CA-125 and HE-4 concentrations were measured, and used to calculate ROMA and CPH-I. The diagnostic accuracy was determined and the receiver operating characteristic curve was plotted. Univariable and multivariable analysis was undertaken to identify predictors of misclassification. Results Eighty-six participants were included in the final analysis, of whom 58 (67%) had benign masses, 23 (27%) had malignant tumors, and 5 (6%) had borderline ovarian tumors. Serum CA-125, HE-4, ROMA, and CPH-I values were significantly higher in malignant tumors than benign lesions. In premenopausal women, HE-4 and ROMA demonstrated the highest diagnostic accuracy with AUC values of 0.938 and 0.942, respectively, along with 75% sensitivity and 100% specificity. In postmenopausal women, the Copenhagen Index demonstrated the highest specificity (94.83%) and AUC (0.924). The predefined clinical cutoffs for CA-125, ROMA, and CPH-I were 35 U/mL, 12.5–14.4%, and 7%, respectively, while study-derived optimal cutoffs using Youden’s index were 29.6 U/mL for CA-125 and 5.3% for CPH-I. Endometriosis and tubercular masses were significant predictors of CA-125 discrepancies. Conclusion HE-4 and ROMA demonstrated improved specificity compared with CA-125 in premenopausal women. The Copenhagen Index demonstrated the highest specificity and AUC in postmenopausal women while offering the practical advantage of being independent of menopausal classification. These biomarkers may serve as useful adjunctive triage tools alongside imaging and clinical assessment to facilitate timely referral to gynecologic oncology services. Ovarian Neoplasms Biomarkers Tumor Mass Screening CA-125 Antigen ROC Curve Sensitivity and Specificity Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 13 Jul, 2026 Reviewers agreed at journal 02 Jul, 2026 Reviewers invited by journal 19 Jun, 2026 Editor invited by journal 19 Jun, 2026 Editor assigned by journal 14 Jun, 2026 Submission checks completed at journal 14 Jun, 2026 First submitted to journal 11 Jun, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-10002273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":663042622,"identity":"9df02495-40df-46f4-9b64-bfc7eaa66dc4","order_by":0,"name":"Nilanchali 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07:25:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-10002273/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-10002273/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":113041557,"identity":"4c9a2cde-8948-4564-9f31-b9c61f587dd8","added_by":"auto","created_at":"2026-06-25 11:52:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":602807,"visible":true,"origin":"","legend":"","description":"","filename":"ROMAupdatedFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-10002273/v1_covered_0081689a-3dca-4af0-8064-afb3ccb55e08.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of CA-125, HE4, ROMA, and Copenhagen Index for Preoperative Risk Stratification of Adnexal Masses in Indian Women: A Prospective Cross-Sectional 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Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ovarian Neoplasms, Biomarkers, Tumor, Mass Screening, CA-125 Antigen, ROC Curve, Sensitivity and Specificity","lastPublishedDoi":"10.21203/rs.3.rs-10002273/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-10002273/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOvarian cancer causes ~ 207,000 deaths annually worldwide (GLOBOCAN 2022), with India bearing ~ 16% of the global burden. Despite screening advances, biomarkers remain essential for triage in low-resource settings. This study assessed CA-125, HE4, Risk of Ovarian Malignancy Algorithm (ROMA), and Copenhagen Index (CPH-I) for distinguishing benign from malignant adnexal masses in Indian women.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study is a single-center, cross-sectional study enrolling participants prospectively conducted at a tertiary center. Serum CA-125 and HE-4 concentrations were measured, and used to calculate ROMA and CPH-I. The diagnostic accuracy was determined and the receiver operating characteristic curve was plotted. Univariable and multivariable analysis was undertaken to identify predictors of misclassification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEighty-six participants were included in the final analysis, of whom 58 (67%) had benign masses, 23 (27%) had malignant tumors, and 5 (6%) had borderline ovarian tumors. Serum CA-125, HE-4, ROMA, and CPH-I values were significantly higher in malignant tumors than benign lesions. In premenopausal women, HE-4 and ROMA demonstrated the highest diagnostic accuracy with AUC values of 0.938 and 0.942, respectively, along with 75% sensitivity and 100% specificity. In postmenopausal women, the Copenhagen Index demonstrated the highest specificity (94.83%) and AUC (0.924). The predefined clinical cutoffs for CA-125, ROMA, and CPH-I were 35 U/mL, 12.5–14.4%, and 7%, respectively, while study-derived optimal cutoffs using Youden’s index were 29.6 U/mL for CA-125 and 5.3% for CPH-I. 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These biomarkers may serve as useful adjunctive triage tools alongside imaging and clinical assessment to facilitate timely referral to gynecologic oncology services.\u003c/p\u003e","manuscriptTitle":"Evaluation of CA-125, HE4, ROMA, and Copenhagen Index for Preoperative Risk Stratification of Adnexal Masses in Indian Women: A Prospective Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-06-25 10:48:06","doi":"10.21203/rs.3.rs-10002273/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-07-13T16:48:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290397332748531609804617006603162375635","date":"2026-07-03T02:59:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-06-19T10:24:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-06-19T09:45:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-06-15T00:40:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-06-15T00:40:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2026-06-11T07:16:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4c1a6f2-c813-417b-826f-e0b57f79f1d9","owner":[],"postedDate":"June 25th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-07-13T16:48:22+00:00","index":36,"fulltext":""},{"type":"reviewerAgreed","content":"290397332748531609804617006603162375635","date":"2026-07-03T02:59:32+00:00","index":35,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-06-25T10:48:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-06-25 10:48:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-10002273","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-10002273","identity":"rs-10002273","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}