Abstract
Introduction:
The Norwegian organized cervical cancer screening program recommends three-yearly cytology starting at age 25, followed by five-yearly human papillomavirus (HPV) testing for women aged 34–69 years. With Norway’s first adolescent-vaccinated cohort entering screening in 2022, improved triage approaches for vaccinated women may be required for the screening program to remain cost-effective and limit overdiagnosis. To help inform revised guidelines for adolescent-vaccinated cohorts, we analyzed the health impact, colposcopy use, and cost-effectiveness of alternative primary HPV triage approaches for women initiating screening in 2023.
Methods:
We used a multi-modeling approach that captured HPV transmission and cervical carcinogenesis to compare alternative triage scenarios for five-yearly primary HPV testing with a status-quo scenario for women born in 1998 (i.e., age 25 in 2023). For each strategy, we estimated the cervical cancer screening and treatment costs per person, number of colposcopy referrals, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We examined 72 scenarios that varied the inclusion and management of women who tested positive for alternative grouped HPV genotypes to either direct colposcopy referral or active surveillance (genotype groups: 16/18, 16/18/45, or 16/18/31/33/45/52/58) as well as variations in wait time for re-testing for positive HPV tests (12/24 or 18/36 months for selected/non-selected genotype risk groups, respectively). We also considered variations in the age that women switch from cytology to HPV-based screening (age 25, 28, 31, or 34 years). Cost outcomes were discounted (4% annually) and presented in 2020 USD (USD1 = NOK9.4004).
Results:
Given benchmarks for severity-specific cost-effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved starting primary HPV-based screening at age 25 with direct colposcopy referral for 16/18-positive women alongside extended re-testing wait times (i.e., 18/36 months) for women referred to triage (ICER of $28,900 per QALY gained). Strategies directly referring women who test positive for additional genotypes to colposcopy yielded ICERs above the maximum threshold in Norway ($90,000 per QALY gained), while the currently-recommended strategy (switching to primary HPV testing at age 34) was dominated and therefore not considered efficient or cost-effective. Among the efficient strategies, only primary HPV-based screening starting at age 28 alongside active surveillance with extended re-testing wait times for all positive women reduced the number of colposcopy referrals compared to the currently-recommended strategy (lifetime risk = 0.002237), but these strategies increased the associated lifetime risk of cervical cancer up to 0.002279.
Conclusions:
As vaccinated cohorts enter screening age in Norway, obtaining more information from an HPV test to improve triage approaches ensures balancing overdiagnosis and resources use among the cohorts of vaccinated women who face a low risk of cervical cancer compared with unvaccinated women. The Norwegian program should consider transitioning the program away from using primary cytology-based screening towards exclusively primary HPV-based screening and use triage approaches to improve program effectiveness and efficiency.