Thesis

English summary 201 9 explore new screening and management approaches that provide good performance in increasingly vaccinated populations with decreasing disease prevalence. Chapter 7 delves into the potential of host-cell methylation markers in identifying vaccinated women with clinically relevant disease, performing a pilot study with FAM19A4 and miR124-2 host-cell methylation markers on 403 cervical samples of vaccinated women aged 25 years. In addition, HPV methylation markers (HPV16 L1, HPV16 L2, HPV18 L2, HPV31 L1 and HPV33 L2) and a host-cell gene (EBP41L3) were evaluated. With these pilot DNA methylation results, it was shown that in vaccinated women host-cell methylation levels were low, with in nearly all vaccinated HSIL cases levels inalterably like controls. It is plausible that among the HPV-vaccinated women most cervical lesions would regress without the need of treatment. However, these results on the potential of host-cell methylation markers to identify vaccinated women with spontaneously regressive lesions from those who will progress, require validation in larger HPV-vaccinated cohorts with an extended age range and follow-up period. Chapter 8 concludes with the general discussion of the findings of this thesis, highlighting the expectations of host-cell DNA methylation markers in the prevention of cervical cancer.

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