Personalised Screening Strategies: RISCC project Redefines Cervical Cancer Prevention
Cervical cancer screening programs have been implemented globally but often follow a “one-sizefits-all” approach. This leads to suboptimal protection, suboptimal resource allocation, and harms.
We spoke to Dr. Johannes Berkhof, the Coordinator of the RISCC project which aims to develop a risk-based screening using screening history, HPV vaccination status, and other relevant risk factors.
Cervical cancer is a significant threat to women worldwide. Despite the availability of preventive measures, the incidence of this disease remains high, claiming thousands of lives each year. In Europe alone, there were 61,000 new cases and 25,000 deaths from cervical cancer in 2018 and cervical cancer incidence continues to rise in several Central and Eastern European regions without organised screening. Additionally, the Netherlands, Sweden, and Finland, where organised screening programs have resulted in positive outcomes in the past, have also witnessed an increased incidence in the last decade. This demonstrates the necessity for more effective screening strategies.
We spoke to Dr. Johannes Berkhof, coordinator of the RISCC (Risk-based Screening for Cervical Cancer) project.
Funded by the European Union’s Horizon 2020 Framework Programme for Research and Innovation, RISCC brings together a diverse consortium of leading researchers in the field of HPV, HPV screening, and HPV vaccination. The consortium’s primary objective is to develop and evaluate Europe’s first risk-
based screening program for cervical cancer. Additionally, RISCC aims to provide opensource implementation tools and contribute to the goal of eliminating cervical cancer. Current screening programs have a high rate of unnecessary colposcopy referrals and a varying number of screening invitations across European countries. These inefficiencies highlight the potential for significant cost savings, estimated at €100 million across Europe. To address these challenges, RISCC advocates for a paradigm shift from the current one-size-fits-all approach to an individualised risk-based screening protocol. In the new approach, the clinical management after an initial screening test will be guided by the risk of cervical cancer, defined by test results, screening history, age, vaccination status and other potential risk factors. “Why would we want to do cervical cancer screening based on individual risks? So far, most of the programs have all used a one-size-fits-all program. So, irrespective of your risk, you always get the same test at fixed intervals. But some women have a much higher risk than other women,
and we would like to account for that. This would lead to less unnecessary activity in low–risk women and lower rates of anxiety. It is also cost-effective because if we invest €2 per woman, we would be able to avoid 12,500 cervical cancer deaths in Europe every year. That is a substantial reduction in the number of cervical cancer deaths” explains Dr. Berkhof. In order to create a risk-based screening program, it is necessary to develop risk profiles for cervical cancer:
Risk profiles in unvaccinated birth cohorts
Cervical cancer screening has been traditionally done through cytological screening with the Pap test. However, this cancer is caused by the human papillomavirus (HPV) infection and its detection via HPV testing has shown significant improvements over the Pap in cervical cancer screening. Data from screening cohorts in Europe and North America demonstrates that switching to HPV screening reduces the risk of precancerous conditions by approximately 70% after a negative screen.
By analyzing data from previous screening rounds, the researchers have observed that the risk of cervical cancer drops after multiple negative test results compared to just one negative HPV test. However, “Various studies show that the risk of pre-cancer after a negative HPV test is about seven times higher if it is preceded by a positive HPV test in the previous round. This illustrates that taking into account the result of the HPV test in the previous round can optimize your screening program” explains Dr. Berkhof.
Data on screening results is collected from seven different HPV screening trials conducted across Europe, including over 150,000 women from the previous CoheaHr project as well as data from screening programs. Some of these trials compare cytology-based screening to HPV-based screening, and they provide the project with new follow-up data spanning up to 20 years after enrollment. Additionally, data is
Influence of other risk factors in risk profiles
There are other risk factors such as poverty, smoking, use of oral contraceptives, and sexual behaviour that may influence the risk of getting an HPV infection or developing (pre)cancer. The researchers will summarize the evidence on the potential significance of these risk factors for a cervical screening program.
Cost-effectiveness
“After we have collected all that evidence, we will use all these risk estimates to develop a model for Europe, that enables us to assess the health benefits of different risk-based screening strategies and weigh them against the cost of implementing these strategies. By tailoring the screening approaches to local European settings, we can identify cost-effective riskbased screening strategies that suit local settings and optimize resource allocation” explains Dr. Berkhof.
all rooted in the concept of risk-based screening.”
utilised from HPV self-sampling trials that compare HPV testing on a sample taken at the clinic by a healthcare professional to HPV testing on a sample taken at home using a self-sampling kit. These selfsampling trials have a follow-up period of approximately ten years. Furthermore, the samples from the self-sampling trials will be used to evaluate the use of molecular tests, specifically DNA methylation, to identify (pre)cancer in HPV-positive women. Currently, HPV-positive women need to visit the healthcare professional for a Pap smear. The use of molecular markers, such as DNA methylation, provides an appealing method to stratify HPV-positive women, as it can be directly performed on the selfcollected specimen.
Risk profiles for HPV-vaccinated birth-cohorts
Risk profiles are also developed for vaccinated birth cohorts. “Vaccination is an important risk factor. We are collecting data from a randomised trial conducted in Finland that involves 80,000 women with known vaccination status who were randomly assigned to either frequent or infrequent HPV screening. We also use observational data from countries where the individual HPV vaccination status is linked to screening outcomes. This allows us to examine the direct and indirect effects of vaccination on screening” says Dr. Berkhof.
RISCC
Risk-based Screening for Cervical Cancer Project Objectives
RISCC aims to introduce a risk-based screening approach to improve the effectiveness and efficiency of cervical cancer screening. By creating risk profiles using data from large trials and screening programs in the general population, the project will develop a more targeted and personalised screening strategy. The goal is to optimize screening algorithms and improve the identification of high-risk individuals for early intervention. This will ultimately contribute to the elimination of cervical cancer as a public health problem.
Project Funding
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847845.
Project Partners
https://www.riscc-h2020.eu/about-riscc/partners/ Contact Details
Pilot implementation trial
Digitalization facilitates implementation of risk-based screening by incorporating patient-specific risk factors and providing personalised recommendations. The project will implement a risk-based screening strategy in a pilot study conducted in Sweden. This strategy will make use of a digital invitation platform, allowing individuals to enroll for risk-based screening and receive invitations through a linked app connected to the screening management database. The pilot trial in Sweden will assess the impact of the digital invitational system on attendance, acceptability, and cost savings in risk-based screening.
Training and dissemination
As part of the tools to facilitate implementation, the consortium is developing an e-learning open-access course through the e-oncologia platform (https://www.e-oncologia.org) on HPV-related content and cervical cancer management. It will teach healthcare professionals and screening managers how to implement HPV risk-based screening. The dissemination of the project’s results via social media and newsletters with HPV-related content, and ESGO-ENGAGe involvement with gynecological cancer survivors aims to increase HPV awareness and the need to improve current screening practices among researchers and the general population.
RISCC daily management: Professor Johannes Berkhof, Project Coordinator Dr. Laurian Jongejan, Program Manager Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands
E: riscc@amsterdamumc.nl : @RISCC_H2020 W: https://www.riscc-h2020.eu/
Prof. Berkhof is head of the Department of Epidemiology and Data Science in Amsterdam University Medical Center. He has over 20 years’ experience in statistical and modelling research with over 200 articles on HPV, methodology, cost-effectiveness, screening, public health and statistics.
Dr. Robles is an epidemiologist at the Cancer Epidemiology Research Program within the Catalan Institute of Oncology. She has over 10 years’ experience in cancer epidemiology and prevention, mainly focused on cervical cancer over the last years.
“Our aim is to help countries and policymakers to develop their HPV screening programs that incorporate various aspects,Prof. Johannes Berkhof Dr. Claudia Robles The RISCC consortium meeting held in Autumn 2022 in Amsterdam.