Article open access publication

Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

International Journal of Cancer, Wiley, ISSN 0020-7136

Volume 143, 3, 2018

DOI:10.1002/ijc.31335, Dimensions: pub.1101172485, PMC: PMC6019150, PMID: 29473162,



  1. (1) German Cancer Research Center, grid.7497.d
  2. (2) Arizona State University, grid.215654.1
  3. (3) Danish Cancer Society, grid.417390.8
  4. (4) Aarhus University, grid.7048.b, AU
  5. (5) Centre for research in epidemiology and population health, grid.463845.8
  6. (6) Institut Gustave Roussy, grid.14925.3b
  7. (7) International Agency For Research On Cancer, grid.17703.32
  8. (8) German Institute of Human Nutrition, grid.418213.d
  9. (9) National and Kapodistrian University of Athens, grid.5216.0
  10. (10) Hellenic Health Foundation, grid.424637.0
  11. (11) University of Milan, grid.4708.b
  12. (12) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  13. (13) University of Naples Federico II, grid.4691.a
  14. (14) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  15. (15) Cancer Registry and Histopathology Unit, ‘Civic – M.P. Arezzo’ Hospital, ASP Ragusa, Italy
  16. (16) Department of Medical Sciences, University of Torino and Human Genetics Foundation – HuGeF, Torino, Italy
  17. (17) Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  18. (18) The Arctic University of Norway, grid.10919.30
  19. (19) Cancer Registry of Norway, grid.418941.1
  20. (20) Folkhälsans Forskningscentrum, grid.428673.c
  21. (21) Karolinska Institute, grid.4714.6
  22. (22) Andalusian School of Public Health, grid.413740.5
  23. (23) CIBER de Epidemiolgía y Salud Pública (CIBERESP), Spain
  24. (24) Instituto Murciano de Investigación Biosanitaria, grid.452553.0
  25. (25) University of Murcia, grid.10586.3a
  26. (26) Catalan Institute of Oncology, grid.418701.b
  27. (27) Centro de Investigación Biomédica En Red (CIBER), Navarra Public Health Institute, Pamplona, Spain. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
  28. (28) Basque Regional Health Department, Public Health Division and BioDonostia Research Institute and CIBERESP, San Sebastian, Spain
  29. (29) Umeå University, grid.12650.30
  30. (30) Department of Surgery, Skane University Hospital, Lund University, Malmö, Sweden
  31. (31) University of Oxford, grid.4991.5
  32. (32) Imperial College London, grid.7445.2
  33. (33) University of Hawaii at Manoa, grid.410445.0
  34. (34) Brigham and Women's Hospital, grid.62560.37
  35. (35) Harvard University, grid.38142.3c


Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.


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