Detection rates of high grade serous ovarian cancers using a clinical non‐invasive prenatal testing platform: potential for ovarian cancer screening

Objectives: Maternal malignancy is a rare but important cause offalse positive results from cell-free (cf) DNA-based non-invasiveprenatal testing (NIPT) for fetal aneuploidy. We investigated theability of a clinical NIPT platform to detect high grade serousovarian cancer (HG-SOC) by analysing plasma cfDNA samplesfrom non-pregnant women with and without cancer. Methods: In this blinded case – control study, plasma DNA from32 cases of HG-SOC [16 early stage (FIGO Stage I-II), and 16advanced stage (FIGO Stage III-IV) cancers] and 32 benign controlswere sequenced and analysed for whole chromosome aneuploidyusing a routine NIPT pipeline. The results were further analysedfor subchromosomal changes using the WISECONDOR algorithm(WIthin-SamplE COpy Number aberration DetectOR)i;segmentalchanges>15 Mb were pre-specified as abnormal calls. Results: Of the 32 cancer cases, 6 had a ”no call” result onthe routine NIPT pipeline and one generated a ‘‘monosomy 18’’result. On WISECONDOR analysis, 13/32 cases had abnormal calls(detection rate 40%, 95% CI 25.5-57.8%), including 6/16 earlystage and 7/16 advanced stage cases. Almost all the 13 cancer caseswith abnormal calls had multiple segmental changes: the genomicaberrations detected in plasma included common imbalancesassociated with HG-SOC (3q, 8q, 12p and chr20 gains; 8p, 9pand 17q losses)ii. Two of 32 (6%, 95% CI,−2.1-14.6%) benigncontrols also had abnormal calls on WISECONDOR analysis. Conclusions: We detected 40% of early and advanced serousovarian cancers in plasma cfDNA using a clinical NIPT platformand an open source bioinformatics algorithm. While not presentlyfeasible as a stand-alone screening test, high throughput plasmaDNA sequencing for circulating tumour DNA could be a potentialcomponent of a multiple marker strategy for the detection of earlyovarian cancer.