Sylvia Kaljouw

Under which realistic circumstances is hrHPV self‐sampling increasing cervical screening effectiveness in a partly vaccinated population? A modelling study

Abstract High‐risk Human Papillomavirus self‐sampling can increase attendance rates for screening. However, observed lower sensitivity and loss to follow‐up of self‐sampling could reduce programme effectiveness when attenders of clinician‐collected sampling switch to self‐sampling. We determined the tipping point for effectiveness (based on life years gained [LYG]) of self‐sampling and the consequences for cost‐effectiveness, taking into account waste by comparing full opt‐out (no waste) to no opt‐out (waste from unused self‐sampling kits). We used the STDSIM‐MISCAN‐Cervix microsimulation model to simulate a population of Dutch women born in 2000 (50% vaccinated [sensitivity analysis: 0–100%], 70% screening attendance [sensitivity analysis: 60–80%]). Self‐sampling deployment strategies (e.g., direct‐mail) were varied by the percentage of original attenders switching to self‐sampling and the percentage of new attendance from non‐attenders. Main outcome measures were LYG and cost‐effectiveness (cost per quality adjusted [QA] LY gained) compared to the current programme. We found that if self‐sampling does not reach non‐attenders, life years cannot be gained. When reaching 10% or 30% of non‐attenders, the tipping point lies at ≤40% and ≤100% switchers to maintain effectiveness, respectively (+4 LYG, +10 LYG). Scenarios were cost‐effective (<€50,000/QALY gained) if at least 10% of non‐attenders were reached. Full opt‐out improved cost‐effectiveness substantially. So, in a partly vaccinated population, self‐sampling deployment strategies need to reach at least 10% of non‐attenders to maintain programme effectiveness and cost‐effectiveness. A well‐functioning opt‐out system further improves cost‐effectiveness by preventing waste.

Should the age range of the Dutch hrHPV‐based cervical cancer screening program be broadened? A modelling study using cohort effects

AbstractIn the Netherlands, women are invited for human papillomavirus (HPV) screening between the ages of 30 and 60 (with conditional screening at age 65). However, an increase in cervical cancer (CC) incidence has been observed in younger women recently. Meanwhile, HPV‐vaccinated cohorts reached the screening age of 30 in 2023. Moreover, increasing healthy life expectancy is a consideration for screening in older age groups. Due to these developments, the starting and ending ages of the HPV screening programs should be reconsidered. Microsimulation model MISCAN‐Cervix was recalibrated for cohort effects using updated CC incidence data. We used this model to calculate the cost‐effectiveness of screening unvaccinated women in birth cohorts 1962–1992 until 65 years old. Additionally, we considered starting screening at 25 for partly vaccinated cohorts (born in 2002–2006). Vaccination effects were calculated using microsimulation model STDSIM. Main outcome measures included cancers prevented, life years gained (LYG), costs, and referrals compared to the current strategy (2027 onwards). Adding screening at age 65 to the current strategy leads to +3.5% cancers prevented, +10.3% referrals, +2.4% LYG and +57.0% costs (cost‐effectiveness ratio: €275,096/LYG). Adding screening at age 25 results in extra cases prevented (+1.3%–5.7%, depending on the target group's vaccination status) and LYG (+0.8%–3.7%), but increases referrals (12.9%–37.1%) and costs (+14.0%–33.1%) (cost‐effectiveness ratio: €120,017–€323,813/LYG). So, screening unvaccinated women at 65 years old and screening women in (partly‐)vaccinated cohorts at age 25 might not represent good value for money.

Cost‐Effectiveness of Computer‐Assisted Cytology in a Primary hrHPV‐Based Cervical Cancer Screening Programme

ABSTRACTBackgroundComputer‐assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost‐effective compared to manual cytology triage in a primary HPV‐based cervical screening programme.MethodsMicrosimulation model MISCAN‐Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost‐effectiveness was evaluated by costs per (quality‐adjusted) life year ((QA)LY) gained.ResultsCAS will be cost‐effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost‐effective strategy compared to manual cytology triage.ConclusionAs we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost‐effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage.

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study

AbstractObjectiveTo calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high‐risk human papillomavirus (hrHPV) screening programme.DesignMicrosimulation study.SettingDutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65.PopulationPartly vaccinated population of 100 million Dutch women.MethodsMicrosimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance.Main outcome measuresHarms (screening tests, unnecessary referrals, treatment‐related health problems), benefits (CIN2+ diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017–2021), second (period 2022–2026) and third (period 2027–2031) rounds of hrHPV‐based screening.ResultsThe number of screening tests and CIN2+ diagnoses decreased from the first to the second round (−25.8% and −23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (−2.7% and −5.3%, respectively). NNS to detect a CIN2+ remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups.ConclusionBoth harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low‐risk women.Tweetable abstract:Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future.