Optimal Cervical Cancer Prevention Policies (CC-PREVENT)
The overarching objective of CC-PREVENT is to optimize resource-use and benefit-harm trade-offs within and between cervical cancer (CC) prevention programs (i.e., vaccination and screening programs) that continue to reduce the burden of cervical cancer in Norway.
Figure 1. Annual changes in the proportion of HPV vaccinated women among Norwegian women in the screening target ages of 25-69 years. The first cohort of girls vaccinated at age 12 years in 2009 will initiate screening at age 25 years in 2022.
The discovery of persistent high-risk human papillomavirus (HPV) as the obligate, viral cause of cervical cancer worldwide has led to innovative HPV-based technologies that are changing the landscape of cervical cancer prevention. This include prophylactic HPV vaccination and sensitive molecular HPV testing for cervical cancer screening.
HPV vaccination is expected to reduce cervical cancer risk among vaccinated individuals by >70%, while HPV-based screening allows for less frequent screening intervals.
These technologies prompt three major questions related to cervical cancer prevention:
1) How to design HPV vaccination programs to accelerate prevention of cervical cancer,
2) How to design screening policies for HPV-vaccinated and unvaccinated women who have different risks of developing cervical cancer,
3) How to integrate vaccination and screening programs.
About the project
CC-PREVENT aims to inform cervical cancer prevention programs that reduce the burden of cervical cancer for all social groups, while ensuring efficient resource use and an acceptable benefit-harm balance within and between cervical cancer control programs (i.e. vaccination and screening).
The analyses conducted in CC-PREVENT will anticipate the changes in the effectiveness and cost-effectiveness of current screening policies in light of the changing landscape of vaccination programs and thereby ensure that the Norwegian cervical cancer screening program remains a responsible public health program.
Findings of CC-PREVENT will prove essential to guide decision-making related to current and future cervical cancer prevention policies, including policy recommendations for both the HPV vaccination and cervical cancer screening programs.
CC-PREVENT will inform Norwegian cervical cancer prevention policies using a disease simulation model-based framework completed in three work packages (Figure 2):
1) Optimal HPV Vaccination Policies,
2) Optimal Screening Policies, and
3) Optimal Integration of Screening and Vaccination
We will use complex and validated disease simulation models from our collaborators at the Harvard Center for Health Decision Science (Harvard T.H. Chan School of Public Health) to project the long-term epidemiologic, health, and economic consequences of alternative interventions (e.g., screening and HPV vaccination strategies) to reduce the burden of cervical cancer (and five additional HPV-related cancers). The Harvard HPV disease simulation models are a part of the US National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISENT) Cervix modeling consortium. For the five policy evaluations outlined in CC-PREVENT, we will use a cost-effectiveness analysis framework to identify strategies that provide good value for money. CC-PREVENT activities will be completed in close dialogue with clinical and policy experts.
While most HPV infections spontaneously regress, a persistent infection can trigger the development of cervical precancers and invasive cancer. Although HPV can cause cancer among both men and women, cervical cancer reflects the largest burden. The long lag time between infection and cancer (usually 10-30 years) allows for the detection and removal of precancers to interrupt the carcinogenic pathway.
The discovery of HPV has led to innovative HPV-based technologies that are changing the landscape of cervical cancer prevention, including primary (HPV vaccination) as well as secondary (screening) prevention approaches. For example, the completion of randomized controlled trials that indicate that HPV testing is more efficacious than cytology as the primary screening method have prompted several countries (e.g., Norway in 2019) to switch to more sensitive primary HPV testing.
In 2009, Norway introduced routine HPV vaccination using the quadrivalent HPV vaccine of pre-adolescent girls (age 12). These “fully” vaccinated girls will initiate screening in 2022 with a dramatically reduced risk of developing cervical cancer (Figure 1, bottom right). In 2016, Norway implemented a temporary “catch-up” vaccination campaign (recommended for women aged ≤26 years) to expedite health benefits (Figure 1, middle). In 2018, Norway introduced a gender-neutral HPV vaccination policy, including both girls and boys aged 12 years in the Norwegian childhood vaccination program.
A student sub-project of CC-PREVENT, “Resource use and economic impact of local and national impact of the new triage algorithm in implementation pilot of primary HPV screening”, involves using de-identified primary data from the Cancer Registry of Norway to conduct a descriptive analysis of the impact of switching to primary screening HPV-test on resource use and total costs during the introduction of the pilot implementation program. This sub-project will explore the expected changes from the gradual national scale-up of primary HPV screening by applying the relative changes in resource use and cost from the pilot implementation program to other regions of Norway. The sub-project completed a DPIA and has received approval from UiO’s Data Protection Officer.
A second student sub-project of CC-PREVENT, "The cost-effectiveness of Opt-in and send-to-all HPV self-sampling among long-term non-attenders to cervical cancer screening in Norway: The Equalscreen randomized controlled trial" is assessing the cost-effectiveness of mailing a human papillomavirus self-sampling (HPV-ss) kit, directly or via invitation to order, compared with mailing reminder letters among long-term non-attenders in Norway. Equalscreen study approval was obtained from the Regional Committees for Medical and Health Research Ethics (2019/111) and Oslo University Hospital’s Data Protection Officer (18/14056). A statement regarding the processing of personal data was also obtained from the Data Protection Officer at Akershus University Hospital. For women in self-sampling arms, the invitation included information that by returning the self-sample, they consented to the subsequent procedures described in the invitation letter. All invited women, including those in the control arm, were informed that they could withdraw from the study at any time. The study was performed in accordance with the Declaration of Helsinki
Cooperation Institutions and Organizations
Harvard T.H. Chan School of Public Health (USA), Norwegian Institute of Public Health, and the Cancer Registry of Norway.
Start - Finish
September 2019- May 2025
Portnoy A, Pedersen K, Trogstad L, Hansen BT, Feiring B, Laake I, Smith MA, Sy S, Nygård M, Kim JJ, Burger EA. Impact and cost-effectiveness of strategies to accelerate cervical cancer elimination: A model-based analysis. Preventive Medicine. 2021 Mar 1;144:106276.
Response. Portnoy A, Pedersen K, Trogstad L, Hansen BT, Feiring B, Laake I, Smith MA, Sy S, Nygård M, Kim JJ, Burger EA. Cost-effectiveness of nonavalent HPV vaccine in Norway considering current empirical data and validation. Preventive medicine. 2021 Sep;150:106688.
Castanon A, Rebolj M, Burger EA, de Kok IM, Smith MA, Hanley SJ, Carozzi FM, Peacock S, O'Mahony JF. Cervical screening during the COVID-19 pandemic: optimising recovery strategies. The Lancet Public Health. 2021 Jul 1;6(7):e522-7.
Smith MA, Burger EA, Castanon A, de Kok IM, Hanley SJ, Rebolj M, Hall MT, Jansen EE, Killen J, O'Farrell X, Kim JJ. Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis. Preventive Medicine. 2021 Oct 1;151:106623.
Pedersen K, Portnoy A, Sy S, Hansen BT, Trope A, Kim JJ, Burger EA. Switching clinic-based cervical cancer screening programs to HPV self-sampling: A cost-effectiveness analysis of vaccinated and unvaccinated Norwegian women. International Journal of Cancer. 2021 Oct 18.
Portnoy A, Nygård M, Trogstad L, Kim JJ, Burger EA. Impact of Delaying Effective and Cost-Effective Policy Decisions: An Example From Cervical Cancer Prevention in Norway. MDM policy & practice. 2022 Jan;7(1):23814683211071093.
Portnoy A, Pedersen K, Nygård M, Trogstad L, Kim JJ, Burger EA. Identifying a Single Optimal Integrated Cervical Cancer Prevention Policy in Norway: A Cost-Effectiveness Analysis. Medical Decision Making. 2022 Mar 8:0272989X221082683.