Risk profiling in cervical cancer screening to reduce unnecessary referrals and follow-up in the triage of hrHPV-positive women

BACKGROUND In 2017, high-risk human papillomavirus (hrHPV) screening with cytology triage was introduced in the Netherlands. This has resulted in twice as many women being referred and an increased number of biopsies and control smears, leading to anxiety and increased costs. Using additional risk factors to triage women after a hrHPV-positive result may help limit the burden of unnecessary follow-up. Additional risk profiling may also prevent that women have to return for a cytological assessment after a positive self-sampling test. OBJECTIVE The current project aims to: 1. Determine the acceptability of additional risk profiling in focus groups, 2. Create risk profiles, based on questionnaire and screening history data, among hrHPV-positive women, and 3. Determine optimal triage scenarios for hrHPV-positive women using a microsimulation model. Risk profiling is expected to optimise the balance between benefits and harms of triage scenarios for hrHPV-positive women compared to the current strategy. PLAN OF INVESTIGATION Objective 1: Women in the screening age range (30-60 years) will be eligible for participation in the focus groups on risk profiling in cervical cancer screening. Barriers and facilitators will be assessed using a semi-structured interview guide with various topics surrounding acceptability. The interview guide will be based on literature and input from professionals. Women will also be asked to specifically discuss information needs regarding risk profiling and acceptability of including factors that may be sensitive in nature. Special attention will be paid to including underserved women, e.g., women with low health literacy, in cooperation with relevant organisations. Objective 2: A prospective cohort study will be performed among hrHPV-positive women (n = ~6,500). All screening participants who test positive for hrHPV during the inclusion period (year: 2022) will be eligible for participation. Data collection will consist of a web-based questionnaire and linkage to the national pathology database (PALGA). The questionnaire will consist of questions about different risk factors for the transition of a hrHPV infection to (pre-)malignant cervical lesions. Potential risk factors include smoking behaviour, parity and age at first birth, oral contraceptive use, personal screening history, and educational attainment. After linkage of the questionnaire data to PALGA, the dataset will be used to develop a robust prediction model for CIN3+ outcomes. We aim to create a simple model that can be easily applied in the screening setting. Objective 3: We will use the microsimulation model MISCAN-cervix to evaluate the harms and benefits of different cervical cancer triage strategies in various risk groups in the Dutch target population. MISCAN-Cervix simulates the individual life histories of a population of women, based on Dutch demographic and hysterectomy data. Different screening and triage strategies can be evaluated in the simulated population to quantify and compare the harms and benefits of each strategy, including the current strategy, compared to a situation without screening. Outcomes of interest will be total number of triage tests, repeat smears, referrals to colposcopy, CIN (1, 2 and 3) diagnoses, cancer incidence, cancer mortality, costs, life-years gained, and QALYs gained compared to a situation without screening. The results of the overall project will be discussed during a multidisciplinary stakeholder meeting, including women from the target population as well as professionals. The aim of the meeting is to evaluate the steps needed for the potential implementation of this type of risk profiling, including ethical implications. RELEVANCE Recently, the State Secretary for Health, Welfare and Sports expressed a serious concern about the number of referrals in the new hrHPV-based programme, which is supported by the organisations that are responsible for executing the programme (RIVM, screening organisations). Factors that influence the risk of developing cervical cancer in hrHPV-positive women can be used to optimise the triage process and thereby reduce unnecessary follow-up and anxiety. Women at the highest risk of developing cervical cancer will be followed up intensively, whereas the number of follow-up tests can be reduced for women at lower risk. This is essential for improving triage in the Dutch programme, but this study will also provide valuable information for comparable international programmes. Finally, the study on the acceptability of risk profiling gives us the opportunity to design a unique programme that clearly reflects and integrates women’s perceptions and needs.