HE4 was the second best marker for invasive tubo-ovarian cancer after CA125 (sensitivity CA125 86%; HE4 73%) in a nested case–control study within the Prostate, Lung, Colorectal and Ovarian cancer screening (PLCO) trial using a single preclinical sample taken within 6 months of diagnosis [20]. This evidence concerns the gene WFDC2 and ovarian carcinoma.