Natural history and screening model for high‐risk human papillomavirus infection, neoplasia and cervical cancer in the Netherlands

Abstract

A simulation model is presented that assumes that persistent infection with high-risk human papillomavirus (hrHPV) is a necessary cause of cervical cancer. For the estimation of the model parameters, data of recent Dutch follow-up studies were reanalyzed. The predicted incidences of cervical cancer, cervical intraepithelial neoplasia (CIN1, CIN2 and CIN3) and abnormal cytology were validated with nationwide figures and population-based screening results. The model predicted a lifetime risk for cervical cancer of 2.9% with a peak at age 48 years. The predicted lifetime risk dropped to 0.4% when attending cervical screening. For women who were not hrHPV infected at 30 years, the lifetime risk was 1.6%. Sensitivity analyses were performed to check natural history assumptions that were only weakly identified from available data sets. The incidence of CIN3 observed with screening appeared a useful clinical end point as the predicted incidence was robust against changes in the sensitivity of cervical cytology and the duration to CIN3. The model can be used to study the healtheconomic benefits that can be achieved in nationwide screening when including an hrHPV test. ' 2005 Wiley-Liss, Inc.Key words: cervical neoplasms; cytology; cost effectiveness; human papillomavirus; longitudinal studies; models; screening Population-based screening is regarded as an effective method for reducing the incidence of invasive cervical cancer. Epidemiologic studies report that in countries where cytologic screening has been implemented, the incidence of cervical cancer has shown a larger decrease than in countries without screening. 1,2 Although many countries subscribe to the necessity of screening, each country has its own screening program and different opinions about the optimal program remain.Because persistent infection with the high-risk human papillomavirus (hrHPV) is the key causative agent of cervical cancer, 3,4 many recent and ongoing longitudinal studies have examined whether a test for detection of hrHPV in addition to cytologic inspection increases the efficacy of screening. 5-9 Combined screening (hrHPV and cytology) leads to an earlier detection of women who are at risk for developing high-grade lesions 10 and has a higher sensitivity for the detection of high-grade lesions. 11 However, hrHPV testing also induces extra screening costs so that the determination of the optimal screening scenario involves an elaborate cost-effectiveness analysis.An attractive way to study the efficacy of different screening scenarios is simulation modeling. 12-16 Simulation enables us to combine the results of several studies, compare a large number of scenarios and provides an assessment of the costs and effectiveness in preventing cancer. A simulation model requires the specification of an underlying natural history model that describes health trajectories of women in an unscreened population. We present a natural history model for women in the Netherlands between 30 and 80 years of age and apply the model to predict the incidence of ne...

Long-term Impact of Human Papillomavirus Vaccination on Infection Rates, Cervical Abnormalities, and Cancer Incidence

“…The multiple high-risk HPV types in Long-term Impact of HPV Vaccination the model may invade, persist, and clear independently, with type-specific progression rates up to CIN3 that were informed by observations from a population-based screening trial of HPV DNA testing. 25,26 We acknowledge the uncertainty that remains in the model parameterization, but feel that our approach represents an improvement (in terms of estimating the vaccination impact on cancer incidence) over existing dynamic models that focus solely on HPV-16, 30 that model a combined HPV-16/18 type, 31 or that group all high-risk HPV types other than 16 and 18. [27][28][29]32 Second, our multitype model accounts for multiple type-specific infections without the need for an explicit hierarchical classification of high-risk HPV types by oncogenicity, thereby naturally admitting the possibility that elimination of vaccine-type HPV can unmask underlying high-risk HPV infections or lesions caused by nonvaccine types.…”

“…The individual-based simulation model of cervical carcinogenesis considers 14 high-risk HPV types (16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 66, and 68). 10,26 For the purpose of the current analysis, the model was adjusted to include type-specific resistance to reinfection and to allow for switching among sexual-activity categories. This ensures that the individual-based model has similar structure and parameterization as the transmission model.…”

Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands

“…As it takes at least 8 -10 years to develop invasive carcinoma of the cervix after infection with hrHPV, we repeated the analyses matching cases with cancer with normal controls 10 years younger (van Oortmarssen and Habbema, 1995;Zielinski et al, 2001;Berkhof et al, 2005). For these analyses, we included women with normal cytology who were sampled during the enrolment phase of the POBASCAM trial, but did not meet the age criteria for population-based cervical screening (n ¼ 58).…”

HPV16/18 vaccination to prevent cervical cancer in The Netherlands: Model‐based cost‐effectiveness

“…The model simulates health trajectories of a cohort of 12-year old girls until they are deceased. The preinvasive part of the model consists of 14 parallel Markov chains corresponding to an infection with HPV 16,18,31,33,35,39,45,51,52, 56, 58, 59, 66, 68. In the model, a woman may have multiple infections at a certain point in time and for example have a HPV18-positive CIN2 and a HPV16-positive CIN3.…”