Evaluation of CIN2/3 Lesion Regression in GynTect(®) DNA Methylation-Marker-Negative Patients in a Longitudinal Study

SIMPLE SUMMARY: Precancerous cervical lesions, especially among young women, are frequently cleared by the immune system. Consequently, immediate surgical treatment is not mandatory and patients are monitored closely for up to 24 months. To avoid anxiety and to allow for a more individualized treatment, molecular markers that could predict the outcome of the lesion would be desirable. Women with a high risk of progression could be identified earlier. In this study, we could show that the majority of lesions that were negative for the cancer-associated methylation markers comprising the test GynTect(®) have regressed over time. ABSTRACT: Cervical intraepithelial neoplasia (CIN) grade 2/3 has a high spontaneous regression rate, especially among women ≤29 years of age. To reduce overtreatment, reliable prognostic biomarkers would be helpful. The main aim of this study was to analyze the negative predictive value of the methylation marker panel GynTect(®) for lesion regression. In this prospective, multicenter, longitudinal observational proof-of-concept study, women aged ≤29 years with histologically confirmed CIN2 (n = 24) or CIN3 (n = 36) were closely monitored without treatment for up to 24 or 12 months, respectively. The outcome was either regression, persistence, or progression of the lesion. For each patient, a single baseline sample (V0) for cytology, hrHPV detection and methylation analysis was taken. In a primary analysis, the negative predictive value (NPV) of a GynTect(®)-negative test result at V0 for regression was determined. We tested the null hypothesis NPV ≤ 70% against the alternative hypothesis NPV ≥ 90%. Twelve of the eighteen GynTect(®)-negative CIN2 patients showed regression (NPV = 67%, 90% CI 44–85%, p = 0.53). Of the 27 GynTect(®)-negative CIN3 lesions, 15 regressed (NPV = 56%, 90% CI 38–72%, p = 0.92). Although the majority of GynTect(®)-negative lesions regressed, the postulated NPV of ≥90% was not observed. 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.