Does IL-6 have a role in ovarian cancer diagnosis?

February 25, 2020

Results of new research led by Australian investigators suggest that interleukin-6 (IL-6) may have a role in diagnosis of ovarian cancer-but not on its own.

Results of new research led by Australian investigators suggest that interleukin-6 (IL-6) may have a role in diagnosis of ovarian cancer-but not on its own. The findings, published in Scientific Reports, are from an exploratory, observational study of promising immune biomarkers alone or in combination with conventional tests.

Methods
The authors hypothesized that existing diagnostic tests for ovarian cancer might be improved by including inflammatory biomarkers in sera. In a training cohort, they tested four existing clinical tests-risk malignancy index (RMI) score and risk of malignancy algorithm (ROMA), CA125 and HE4-and a panel of 28 immune-soluble biomarkers in sera from 66 patients undergoing surgery for suspected ovarian cancer. Of them, 33 had newly diagnosed high-grade serious ovarian cancer (HGSOC), 12 had benign ovarian masses, and the control group was 21 women undergoing risk reduction surgery for a known genetic mutation or a strong family history of ovarian and/or breast cancer. 

In an independent validation cohort of 69 patients, the researchers then analyzed the six most promising immune biomarkers alone or in combination with the conventional tests. Of the women, 25 had HGSOC, 25 had a benign ovarian mass, and 19 were healthy volunteers.

Findings
IL-6 was identified as the main driver of variability followed closely by conventional diagnostic tests. Median sera IL-6 levels were higher in patients with HGSOC than in those with a benign mass or controls with normal ovaries (28.3 vs. 7.3 vs. 1.2 pg/mL;< 0.0001). The combination of IL-6 further improved the overall predictive probability of the conventional tests.

Modeling a two-step triage of women with a suspicious ovarian mass, the authors found that when an IL-6 level higher than 3.75 pg/mL was used as a primary triage followed by CA125 or RMI score, ovarian cancer could be identified in patients with a misclassification rate of 4.54% to 3.03%, versus 9.09% to 10.60% for CA125 or RMI score alone. IL-6 at that level, the authors said, had a sensitivity of 100%, specificity of 76.8%, positive predictive value of 69.7%, and negative predictive value of 100%. A similar improvement in diagnostic sensitivity with the addition of IL-6 measurement was seen in the validation cohort. 

Conclusions
The researchers concluded that “IL-6 in combination with conventional tests may be a useful clinical biomarker for triage of patients with a suspected malignant ovarian mass.” Theirs, they believe, is the only study to assess the diagnostic value of IL-6 in sera alone and in combination with RMI and ROMA, and CA125 and HE4 in patients with advanced HGSOC. They said that further studies should be done, including in patients with earlier-stage disease, to explore and expand upon the potential usefulness of adding IL-6 to routine diagnostic tests for ovarian cancer.