A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer

Published:November 02, 2015DOI:


      Ovarian cancer is common and has significant morbidity and mortality, partly because it is often diagnosed at a late stage. This study sought to determine the accuracy of individual symptoms and combinations of symptoms for the diagnosis of ovarian cancer.

      Evidence acquisition

      MEDLINE was searched, identifying 2,492 abstracts, reviewing 71 articles in full, and ultimately identifying 17 studies published between 2001 and 2014 that met the inclusion criteria. Data were abstracted by two researchers, and quality was assessed using the QUADAS-2 criteria adapted to the study question. Bivariate random effects meta-analysis was used where possible, and heterogeneity and threshold effects were explored using receiver operating characteristic curves. Data were analyzed in 2015.

      Evidence synthesis

      Most studies were at high risk of bias, primarily because of case-control design or differential verification bias. The highest positive likelihood ratios (LRs+) were found for presence of abdominal mass (LR+, 30.0); abdominal distension or increased girth (LR+, 16.0); abdominal or pelvic pain (LR+, 10.4); abdominal or pelvic bloating (LR+, 9.3); loss of appetite (LR+, 9.2); and a family history of ovarian cancer (LR+, 7.5). No symptoms were helpful at ruling out ovarian cancer when absent. The Ovarian Cancer Symptom Index was validated in five studies and (after excluding one outlier with different inclusion criteria) was 63% sensitive and 95% specific (LR+, 12.6; LR–, 0.39). Two other symptom scores had not been validated prospectively.


      Several individual signs and symptoms significantly increase the likelihood of ovarian cancer when present. More work is needed to validate decision rules and develop new decision support tools integrating risk factors, symptoms, and possibly biomarkers to identify women at increased ovarian cancer risk.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Preventive Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jelovac D.
        • Armstrong D.K.
        Recent progress in the diagnosis and treatment of ovarian cancer.
        CA Cancer J Clin. 2011; 61: 183-203
        • Salehi F.
        • Dunfield L.
        • Phillips K.P.
        • Krewski D.
        • Vanderhyden B.C.
        Risk factors for ovarian cancer: an overview with emphasis on hormonal factors.
        J Toxicol Environ Health B Crit Rev. 2008; 11: 301-321
        • Brody L.C.
        • Biesacker B.B.
        Breast cancer susceptibility genes.
        BRCA1 and BRCA2. Medicine (Baltimore). 1998; 77: 208-226
        • Buys S.S.
        • Partridge E.
        • Black A.
        • et al.
        Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Trial.
        JAMA. 2011; 305: 2295-2303
        • Bankhead C.R.
        • Kehoe S.T.
        • Austoker J.
        Symptoms associated with diagnosis of ovarian cancer: a systematic review.
        BJOG. 2005; 112: 857-865
        • Jayde V.
        • White K.
        • Blomfield P.
        Symptoms and diagnostic delay in ovarian cancer: a summary of the literature.
        Contemp Nurse. 2009; 34: 55-65
        • Whiting P.F.
        • Rutjes A.W.
        • Westwood M.E.
        • et al.
        QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.
        Ann Intern Med. 2011; 155: 529-536
        • Ebell M.H.
        • Culp M.
        • Lastinger K.
        • Dasigi T.
        A systematic review of the bimanual examination as a test for ovarian cancer.
        Am J Prev Med. 2015; 48: 350-356
        • Friedman G.D.
        • Skilling J.S.
        • Udaltsova N.V.
        • Smith L.H.
        Early symptoms of ovarian cancer: a case-control study without recall bias.
        Fam Pract. 2005; 22: 548-553
        • Rossing M.A.
        • Wicklund K.G.
        • Cushing-Haugen K.L.
        • Weiss N.S.
        Predictive value of symptoms for early detection of ovarian cancer.
        J Natl Cancer Inst. 2010; 102: 222-229
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
      1. Macaskill P, Gatsonis C, Deeks JJ, Harbord RM, Takwoingi Y. Analysing and presenting results. In: Deeks JJ, Bossuyt PM, Gatsonis C, eds. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 1.0. The Cochrane Collaboration; 2010: Chapter 10.

        • Hamilton W.
        • Peters T.J.
        • Bankhead C.
        • Sharp D.
        Risk of ovarian cancer in women with symptoms in primary care: population based case-control study.
        BMJ. 2009; 339: b2998
        • Grewal K.
        • Hamilton W.
        • Sharp D.
        Ovarian cancer prediction: development of a scoring system for primary care.
        BJOG. 2013; 120: 1016-1019
        • Macuks R.
        • Baidekalna I.
        • Donina S.
        Comparison of different ovarian cancer detection algorithms.
        Eur J Gynaecol Oncol. 2011; 32: 408-410
        • Macuks R.
        • Baidekalna I.
        • Donina S.
        Diagnostic test for ovarian cancer composed of ovarian cancer symptom index, menopausal status and ovarian cancer antigen CA125.
        Eur J Gynaecol Oncol. 2011; 32: 286-288
        • Hippisley-Cox J.
        • Coupland C.
        Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm.
        BMJ. 2011; 344: d8009
        • Collins G.S.
        • Altman D.G.
        Identifying women with undetected ovarian cancer: independent and external validation of QCancer® (Ovarian) prediction model.
        Eur J Cancer Care (Engl). 2013; 22: 423-429
      2. Behtash N, Ghayouri Azar E, Fakhrejahani F. Symptoms of ovarian cancer in young patients 2 years before diagnosis, a case-control study. Eur J Cancer Care (Engl). 2008;17(5):483–487. 10.1111/j.1365-2354.2007.00890.x.

        • Riman T.
        • Dickman P.W.
        • Nilsson S.
        • et al.
        Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study.
        Am J Epidemiol. 2002; 156: 363-373
        • Andersen M.R.
        • Lowe K.A.
        • Goff B.A.
        Value of symptom-triggered diagnostic evaluation for ovarian cancer.
        Obstet Gynecol. 2014; 123: 73-79
        • Pavlik E.J.
        • Saunders B.A.
        • Doran S.
        • et al.
        The search for meaning—Symptoms and transvaginal sonography screening for ovarian cancer: predicting malignancy.
        Cancer. 2009; 115: 3689-3698
        • Lim A.W.
        • Mesher D.
        • Gentry-Maharaj A.
        • et al.
        Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes.
        J Natl Cancer Inst. 2012; 104: 114-124
        • Andersen M.R.
        • Goff B.A.
        • Lowe K.A.
        • et al.
        Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer.
        Gynecol Oncol. 2010; 116: 378-383
        • Andersen M.R.
        • Goff B.A.
        • Lowe K.A.
        • et al.
        Combining a symptoms index with CA 125 to improve detection of ovarian cancer.
        Cancer. 2008; 113: 484-489
        • Goff B.A.
        • Mandel L.S.
        • Melancon C.H.
        • Muntz H.G.
        Frequency of symptoms of ovarian cancer in women presenting to primary care clinics.
        JAMA. 2004; 291: 2705-2712
        • Vine M.F.
        • Calingaert B.
        • Berchuck A.
        • Schildkraut J.M.
        Characterization of prediagnostic symptoms among primary epithelial ovarian cancer cases and controls.
        Gynecol Oncol. 2003; 90: 75-82
        • Olson S.H.
        • Mignone L.
        • Nakraseive C.
        • Caputo T.A.
        • Barakat R.R.
        • Harlap S.
        Symptoms of ovarian cancer.
        Obstet Gynecol. 2001; 98: 212-217
        • Lurie G.
        • Thompson P.J.
        • McDuffie K.E.
        • Carney M.E.
        • Goodman M.T.
        Prediagnostic symptoms of ovarian carcinoma: a case-control study.
        Gynecol Oncol. 2009; 114: 231-236
        • Goff B.A.
        • Mandel L.S.
        • Drescher C.W.
        • et al.
        Development of an ovarian cancer symptom index: possibilities for earlier detection.
        Cancer. 2007; 109: 221-227
        • McIsaac W.J.
        • Goel V.
        • To T.
        • Low DE.
        The validity of a sore throat score in family practice.
        CMAJ. 2000; 163: 811-815
        • Ebell M.H.
        • Shinholser J.
        What are the most clinically useful cutoffs for the Alvarado and pediatric appendicitis scores? A systematic review.
        Ann Emerg Med. 2014; 64: 365-372
        • Wells P.S.
        • Anderson D.R.
        • Rodger M.
        • et al.
        Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer.
        Ann Intern Med. 2001; 135: 98-107