168 Chapter 8 The studies performed and described in this thesis evaluated host-cell DNA methylation markers for use in cervical cancer screening, with the prospect to facilitate full molecular screening on self-collected samples. In this chapter, the findings obtained from the studies conducted within this thesis are discussed in conjunction with one another and in the context of the available literature. Additionally, the avenues for future research are discussed, providing valuable insights for further exploration in the field. 8.1 METHYLATION BIOMARKERS FOR EARLY DETECTION OF CERVICAL CANCER A biomarker for cervical cancer screening should possess several important characteristics (Figure 8.1) 1, 2: 1. It should exhibit a strong correlation with the disease and provide a lead-time advantage over clinical diagnosis, enabling early detection and intervention before the onset of symptoms. Changes in the measured level of the biomarker should correlate with the disease stage, displaying variations across different cervical intraepithelial neoplasia (CIN) grades and cervical cancer; 2. It should demonstrate high clinical sensitivity, enabling the detection of early stages of cervical cancer and advanced CIN lesions (CIN2 or CIN3) with a low false-negative rate. The biomarker should also exhibit high clinical specificity, ensuring minimal false-positive results, unnecessary follow-up procedures and associated stress; 3. The biomarker should be stable, showing minimal variation when measured in different sample types and storage conditions and it should exhibit high reproducibility, meaning that it can be consistently measured across different laboratories and Criteria for an ideal biomarker for cervical cancer screening Correlation with clinical outcome Sensitive and specific Accurate and reproducible Cost-effective Frequency Test results False Positive Without disease With disease 100% Sensitivity Most accurate 100% Specificity False Negative Figure 8.1 Criteria for an ideal biomarker for cervical cancer screening.
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