Estimating the age distribution of disease-causal HPV infection in women with high-grade cervical intraepithelial neoplasia in Denmark, Estonia, Norway, Slovenia, and Sweden - A modeling study

Sep 23, 2026

The age distribution of disease-causal human papillomavirus (HPV) infections leading to high-grade cervical intraepithelial neoplasia (CIN2+) remains insufficiently characterized across Europe. This study estimates the age at acquisition of disease-causal HPV among women diagnosed with CIN2+ in Denmark, Estonia, Norway, Slovenia, and Sweden. A previously published discrete event simulation model was modified and calibrated by comparing predicted and observed CIN2+ age distributions using a chi-square goodness-of-fit test. Scenario and sensitivity analyses supported robust median age and age-specific risk estimates, informing vaccination targeting.

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RESEARCH ARTICLE Estimating the age distribution of disease-causal HPV infection in women with high-grade cervical intraepithelial neoplasia in Denmark, Estonia, Norway, Slovenia, and Sweden: A modeling study Ugne Sabale a, Alhaji Cherifb, Stefano Valentec, John Cook d, Manisha Yadav d, Gargi Baluni d, Marta del Pinoe, Andrea Marcellusif, and Xuedan You g aValue & Implementation Outcomes Research, MSD, Vilnius, Lithuania; bHealth Economic and Decision Sciences, Merck & Co., Inc., Rahway, NJ, USA; cValue & Implementation Global Medical and Scientific Affairs, MSD, Rome, Italy; dEconomic Modeling and Adaptations, Peritia, Morrisville, NC, USA; e Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; fDepartment of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Milan, Italy; gValue & Implementation Outcomes Research, Merck & Co., Inc., Rahway, NJ, USA ABSTRACT The age distribution of disease-causal human papillomavirus (HPV) infections that lead to high-grade cervical intraepithelial neoplasia (CIN2+) is not well understood in Europe. The objective of this study was to estimate the age at acquisition of disease-causal HPV infection in women diagnosed with CIN2+ in Denmark, Estonia, Norway, Slovenia, and Sweden. A previously published discrete event simulation model was modified to estimate the age of disease-causal HPV infection for females diagnosed with CIN2+ by comparing predicted and observed age distributions of CIN2+ diagnoses using a chi-square goodness-of-fit test. Scenario and sensitivity analyses were also performed. The predicted median age (years) of disease-causal HPV infection was 23.69 in Denmark, 26.73 (narrow case definition for CIN2+ diagnosis) and 28.34 (broad definition) in Estonia, 29.32 in Norway, 32.03 in Slovenia, and 26.33 in Sweden. The percentage of women aged over 26 and 45 years with a predicted causal HPV infection was 42.7%/8.1%(26/45 years) in Denmark, 52.8%/9.0%(narrow definition) and 57.9%/12.7%(broad definition) in Estonia, 64.7%/11.9% in Norway, 72.3%/21.4% in Slovenia, and 51.2%/9.4% in Sweden. Model results were robust to variations in inputs and parametrization tested in scenario and sensitivity analyses. A considerable proportion (42.7–72.3%) of causal HPV infections are projected to occur in women over age 26, while 8.1%–21.4% are projected to occur in women over the age of 45. These findings highlight a need to consider HPV vaccination for previously unvaccinated women to reduce the burden of CIN2+ and cervical cancer. PLAIN LANGUAGE SUMMARY Human papillomavirus (HPV) is highly prevalent worldwide, affecting an estimated 80% of individuals at some point in their lives. While most infections clear on their own, people can acquire new HPV infections with the same genotype and a different genotype due to insufficient natural immunity. Persistent infection with HPV can lead to the development of cervical intraepithelial neoplasia (CIN), which may progress to cervical cancer. Understanding the age at which HPV infections that later cause serious cervical disease are acquired is essential for identifying the most appropriate target ages for vaccination policies among adults not previously vaccinated for HPV. In this study, we used a published discrete event simulation model to estimate the age at which women acquired HPV infections that progressed to a diagnosis of CIN2+ in Denmark, Estonia, Norway, Slovenia, and Sweden. The predicted median age (years) of disease-causal HPV infection was 23.69 in Denmark, 26.73 (narrow case definition for CIN2+ diagnosis) and 28.34 (broad definition) in Estonia, 29.32 in Norway, 32.03 in Slovenia, and 26.33 in Sweden. Between 43%(Denmark) and 72%(Slovenia) of HPV infections leading to CIN2+ were estimated to occur after age 26, while approximately 8%(Denmark) to 21%(Slovenia) were estimate

FAQs

What is the main objective of this study?

To estimate the age at acquisition of disease-causal HPV infection in women diagnosed with CIN2+ in five European countries (Denmark, Estonia, Norway, Slovenia, and Sweden).

How was disease-causal HPV infection age estimated?

By modifying a previously published discrete event simulation model and fitting predicted versus observed CIN2+ age distributions using a chi-square goodness-of-fit test, with scenario and sensitivity analyses.

What do the results suggest about HPV infection risk by age?

A considerable share of disease-causal HPV infections projected to lead to CIN2+ occur after age 26 (about 42.7–72.3%), and after age 45 (about 8.1–21.4%).

How do the findings relate to HPV vaccination?

They highlight a need to consider HPV vaccination for previously unvaccinated women to reduce the burden of CIN2+ and cervical cancer, including adults beyond typical routine vaccination targets.

Sep 23, 2026

Uploaded by Taylor Morgan