TEST:

GynTect®

The methylation of ZNF671 is measurable in cervical FFPE material and has prognostic value. Since ZNF671-methylated samples are most likely to be progressing, we recommend the closer monitoring of patients with GynTect®-positive test results.

ZNF671m within the GynTect® panel demonstrates robust triage performance in diagnosing CIN3 + cases, with efficacy comparable to the full panel. These findings suggest that ZNF671m could be a promising alternative for cytologic triage, warranting further validation.

The GynTect six-gene methylation test provides higher diagnostic accuracy than cervical cytology in the triage of HPV-positive women. Its superior sensitivity and specificity make it a valuable tool for improving risk stratification in HPV-based cervical cancer screening. These findings support the integration of methylation-based testing into screening programs to enhance diagnostic precision and optimize patient management.

The findings suggest that the methylation markers comprising GynTect® may be suitable for detecting vulvar neoplasia, as they exhibit high sensitivity. Nonetheless, adjustments are needed for comparable specificity. Lichen should be considered in result interpretation, and the kit should be used with caution for patients with lichen. Moreover, we observed methylation changes as an early event with the highest positivity of VLSIL. Surprisingly, changes in methylation pattern are not as local as presumed. Cervical SIL led to changed methylation in the vulva. Patients with positive kit results should be monitored regularly for all genital dysplasia. This sheds new light on the epigenetics in cancer.

Cervi-M and GynTect are suitable for application in developing countries due to their superior specificity and PPV. However, more studies are needed to confirm these conclusions.

This study underscores the potential of GynTect® in predicting histology outcomes of post-LEEP specimens, thereby showcasing its promising ability to assist clinicians in selecting appropriate therapeutic regimens for patients with HSIL.

Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance.

This new panel, consisting of ITGA4, ASCL1, and FAM19A4, has a sensitivity of 84% and a specificity of 70%, similar to our previously identified panel (ANKRD18CP, LHX8, and EPB41L3). Thus, in addition to our previously identified panel, the combination of ITGA4, ASCL1, and FAM19A4 showed good diagnostic performance and potentially can replace cytology, thereby avoiding additional doctor's visits for many women worldwide and reducing the time for decision-making for referral to the gynecologist.

For initially GynTect-positive patients both hrHPV and GynTect® assays detect recurrent disease with similar sensitivity but the GynTect® assay has a significantly higher specificity. A future study will have to show whether cytology/GynTect® co-testing will out-perform cytology/hrHPV co-testing in post-treatment surveillance for this subgroup of CIN3 patients.

"oncgnostics GmbH will present its molecular biological cancer diagnostics, its products and current study results at MEDICA, the largest trade fair in the medical industry. Oncgnostics develops patented, highly informative biomarkers. This technology improves existing cervical cancer diagnostics and also, using liquid biopsy, lays the foundation for early detection of head and neck tumours."

"The Hong Kong-based company Grande Bio-tech Co. Ltd. is making a seven-digit Euros investment in the Jena-based diagnostic company Oncgnostics GmbH. Oncgnostics has developed the cancer diagnostic Gyntect for the reliable detection of cervical cancer...Following the successful launch of Oncgnostics’ test in China, Grande Bio-tech Co. Ltd. has decided to make a financial commitment. The goal now is to expand the distribution of tests developed by Oncgnostics in the ASEAN countries."

Thus, the clinical relevance for an implementation of the GynTect assay for patients undergoing watchful waiting remains questionable. Further studies with longer observation periods should be undertaken.