Cost-Effectiveness of DNA Methylation as Triage for Cervical Cancer Screening in Hong Kong: A Modelling Study

OBJECTIVES: Methylation of human genes is strongly associated with cervical intraepithelial neoplasia (CIN) and cancer and has been proposed as a potential replacement for cytology in screening triage. This study assessed the cost-effectiveness of this triage method to inform accessible, affordable, and acceptable cervical cancer screening strategies.

METHODS: We utilized a hybrid model which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of five strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (methylation or cytology [LBC]). We considered a cohort of the female population as of the base year 2022. Life years, quality-adjusted life years (QALYs), and costs of screening and treatment were estimated from the healthcare provider’s perspective and were discounted by 3% annually till the year 2050. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US$49,022). Probabilistic and one-way sensitivity analyses were conducted.

RESULTS: Compared with the current strategy in Hong Kong (5-yearly physician-HPV sampling with LBC triage), all strategies using methylation as a triage method are cost-effective. Methylation incorporating self-sampling is optimal, resulting in more incremental QALYs gained (159 and 212 per 100,000 individuals for 5- and 3-yearly screening interval) and less costs incurred (savings of US$4.6 million and US$2.8 million per 100,000 individuals for 5- and 3-yearly screening interval). Irrespective of relative performance, methylation following self-sampling is cost-saving. When the relative performance of LBC approaches 1.3 times that of methylation, methylation based on physician-HPV sampling is not cost-effective compared to current strategy in Hong Kong.

CONCLUSIONS: Within an HPV primary screening program that uses methylation for triage is a cost-effective alternative to cytology. It may eventually directly complement or replace cytology as a one-step molecular diagnostic and prognostic test.