Introduction/Background Endometrial carcinoma (EC) is traditionally diagnosed by histopathological assessment of an endometrial biopsy, leaving up to 30% of patients undiagnosed due to technical failure of the biopsy procedure or an inadequate amount of tissue. The aim of the current study is to assess whether mutational analyses of cervical cytology including self-samples or pipelle endometrial biopsies can improve the diagnostic accuracy of traditional histopathological diagnosis of EC.

Methodology A prospective multicentre cohort study was performed in three hospitals in the Netherlands. Patients surgically treated for EC or a benign gynecological condition (control group) were included. A Pap brush sample, a cervicovaginal self-sample, a pipelle endometrial biopsy and the surgical specimen of the endometrial carcinoma (endometrial carcinoma group) or normal endometrium (control group) were obtained. A targeted next-generation sequencing panel was used to analyze these samples for mutations in eight genes.

Diagnostic accuracy was determined by calculating sensitivity, specificity and predictive values.

Results Fifty-nine EC patients and 31 control patients were included. In these patients traditional histopathological diagnosis by pipelle had a sensitivity of 78.9% and a specificity of 100%. For EC patients, 96.6% of surgical specimens contained at least 1 mutation. Mutational analysis of Pap brush samples, self-samples, and pipelle endometrial biopsies yielded a sensitivity of 78.0%, 67.3% and 96.5% with a specificity of 96.8%, 96.8% and 93.5%, respectively. Combining these three methods individually with histopathological pipelle endometrial biopsy evaluations yielded a sensitivity of 95.8%, 93.0% and 96.5, respectively.

Conclusion This study has shown that mutational analysis of either cervical cytology, self-samples or pipelle endometrial biopsies improves diagnosis of EC, and is feasible for detection of endometrial pathology. Prospective validation will support implementation in routine clinical practice.

Disclosure M.L.: advisory board AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen pharmaceuticals, Roche; sponsored research by Astra Zeneca, Bristol-Myers Squibb, llumina; royalties by Nimagen. Furthermore, no completing interests were declared.