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

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. What's new? Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer‐specific as expected.