Periodic Reporting for period 3 - VALID-SCREEN (Validation of PreCursor-M for enhanced Cervical (Pre)Cancer detection)
Reporting period: 2017-07-01 to 2019-03-31
DNA methylation analysis of genes involved in CC development represents an important change in the concept of treatment of CIN2/3. A positive methylation test reflects a cancer-like methylation-high pattern. This methylation pattern can be used as a biomarker for the detection of advanced lesions, defined as CIN2/3 lesions associated with a duration of HPV infection >5years and having many chromosomal alterations. These advanced CIN lesions (i.e. part of the CIN2 and most CIN3 lesions) have a high short-term risk of progression to CC and are in need of treatment [Steenbergen et al. Nat Rev Cancer 2014]. This concept fits well with knowledge in the field that CIN2/3 lesions are heterogeneous, both in clinical behavior and with respect to (epi)genetic alterations. For instance, most CIN2/3 lesions at young age (<30 years) will not develop into cancer and mainly regress. This means that the methylation-negative CIN2 and CIN3 lesions, which are detected by current cytology and/or HPV testing, are in fact early lesions with a low chance of progression and may not need treatment within 1-3 years. The use of DNA methylation analysis can reduce overdiagnosis and overtreatment, which is especially important for women at fertile age. To translate this new view - which can be seen as a paradigm shift in the treatment of CIN lesions - to profound benefits to women and for the economics of healthcare, the Valid-screen project has played an important role. The project enabled the collaboration with several international European laboratory sites with well-documented clinical specimens to perform the necessary clinical validation studies to support the new concept and enforce the paradigm shift.