Cervical cancer prevention research

Cervical cancer is the fourth most common cancer in women worldwide, even though it is preventable if detected in a precancerous state. In May 2018, the WHO director-general launched a call for action to eliminate cervical cancer and urged to embed services in strong health systems aimed at delivering universal health coverage.

Primary and secondary prevention in the Netherlands

Over the past decade, the options available for the prevention of cervical cancer have changed tremendously. The resulting policy questions have been addressed in our modeling work, which has directly influenced public health decision making.

Until recently, cytological screening – the so-called “Pap smear” –  was the only means for cervical cancer prevention and population-based screening programs have reduced the incidence of cervical cancer in most developed countries. The finding that a virus, the human papillomavirus (HPV), is causally associated with cervical cancer has led to the development of two new prevention–methods: an HPV vaccine and HPV-based screening.

Cervical cancer screening in the Netherlands. Source: https://www.rivm.nl/en/cervical-cancer-screening-programme/professionals/programme-characteristics

Currently, the Dutch screening program consists of five-yearly cytological screening among women aged 30 to 60.  In 2016, the Netherlands will change to a primary HPV-based screening program among the same age-group. The screenings interval will however be extended to 10 years among women over the age of 40 who have a negative screening test result.

In addition to screening, an HPV vaccination program was implemented in 2009 – targeting girls aged 12 years, and with a catch-up program in 2009 only among girls aged 13-16 years. Almost 60% of girls in the targeted cohorts are vaccinated. The first vaccinated girls will enter the screening program in 2023. An important question is what the intensity of screening needs to be among vaccinated cohorts and how we can provide a screening program that takes into account the differential risk on cervical cancer in vaccinated women and unvaccinated women.

The Risk-based Screening for Cervical Cancer (RISCC) Project

Overview of the risk-based screening for cervical cancer (RISCC) project.

The RISCC project is a multidisciplinary consortium of key researchers in the field of HPV, HPV screening and HPV vaccination, which aims to develop and evaluate the first risk-based screening program for cervical cancer, provide open-source implementation tools and contribute to the elimination of cervical cancer in Europe.

Many European countries have already implemented organized cervical screening and about 70% of EU citizens have access to an organized program, yet cervical cancer incidence has still increased over the last decade. Therefore, we need more effective screening.

Further, after the introduction of primary HPV-based screening, most screening programs reported a high proportion of unnecessary colposcopy referrals of about 80 to >90% and detection of low-grade lesions. Therefore, we need more efficient screening.

Directing screening resources to those most at risk of high-grade cervical lesions or invasive cervical cancer is one way to achieve more effective and efficient screening. However, at the moment most screening programs use one-size-fits-all protocols. Our part of the RISCC project (Work Package 2) will investigate options for risk-based screening and evaluate the performance of different triage strategies of HPV-positive.

HPV modelling

Simplified flowchart of the HPV model. HPV+: HPV positive, CIN: Cervical Intraepithelial Neoplasia

Our team has developed static and dynamic microsimulation models reflecting both the natural history of cervical cancer and the HPV infection. The models include parameters for the risk on HPV infection, the persistence or clearance of infection and the subsequent trajectory of (pre-) cancerous lesions. Furthermore, the interaction of vaccination and screening with the different infection/disease stages can be simulated. We have used these models to estimate (cost-) effectiveness of girls-only HPV vaccination and of HPV-based screening – and our results have been instrumental to the National Health Council in the decision-making process for a population-based vaccination program and a revision of the screening program. Building on these models, we are currently evaluating aspects of improvement for the vaccination program and its optimal integration with the screening program.

In addition to the mathematical modeling, we also perform epidemiological modeling for impact assessment and develop new statistical methods to answer more methodological research questions. In this manner we continuously improve our models.