Improving population-based cervical cancer screening using DNA methylation markers in self-samples

Improving population-based cervical cancer screening using DNA methylation markers in self-samples
The goal of the Dutch cervical cancer screening programme is the early detection of cervical cancer. The presence of human papillomavirus (HPV) in cervical smears or self-sampling material is used as the primary test, followed by cytology triage testing of HPV-positive women. However, HPV-positive women using a self-sampling device need to visit a general practitioner for an additional cervical smear for cytology. This visit is often unwelcome, causes delays, and lowers participation. This thesis focussed on the development of a triage test that can be performed directly on the same self-sample.
Several DNA methylation markers were investigated on self-samples and a three-marker panel with the highest sensitivity and specificity was selected. This three-marker panel was validated on a large cohort of HPV-positive self-samples from the population-based screening programme and proved a reliable alternative for cytology to detect disease (CIN3+).
Not all women participate in the Dutch screening programme. The experiences of women that participated in the screening programme were collected and evaluated to improve the participation rates. Self-sampling was appreciated for its comfort and ease of use, while concerns about correct usage and test reliability discouraged women.
Finally, the cost-effectiveness of the use of the three-marker panel compared to the current triage test (cytology) was evaluated and turned out to be comparable.
In conclusion of this thesis of Jolien de Waard, a triage test based on DNA methylation could eliminate the additional GP visit and enable faster referral to a gynaecologist. Moreover, it offers greater convenience for women, reduces costs, and shows good performance to detect CIN3+.