A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada

While cervical cancer cases in Canada have decreased recently due to cytology primary screening, cervical cancer remains a relatively common and preventable cause of cancer in women. Cervical cancer is primarily caused by persistent genital infection with high-risk human papillomaviruses (HR-HPV). Ontario Health has been evaluating implementing HPV-based testing in cervical screening.

A decision tree model was developed to evaluate the impact of using a similarly sensitive, but more specific, mRNA HR-HPV assay (Aptima HR-HPV assay) compared to a DNA HR-HPV assay (Hybrid Capture 2 HPV assay) in a hypothetical cervical screening algorithm in Ontario, Canada. Results indicated that screening using an mRNA assay could yield cost savings of $4M CAD and a reduction in unnecessary colposcopies, HPV, and cytology tests. These results indicate that the choice of HR-HPV test is important when implementing a primary HPV screening program to avoid unnecessary resource use and cost, which will benefit both women and healthcare providers.

Weston G, Dombrowski C, Steben M, et al.A health economic model to estimate the costs and benefits of an mRNA vs DNA high-risk HPV assay in a hypothetical HPV primary screening algorithm in Ontario, Canada. Preventive Medicine Reports [Internet]. 2021 Sep 1 [cited 2021 Jul 29];23:101448. Available from: https://www.sciencedirect.com/science/article/pii/S2211335521001388

Evaluating the benefits and costs of using an mRNA versus DNA HR-HPV assay in the National Cervical Screening Programme in the Netherlands

Persistent infection with high-risk human papillomavirus (HR-HPV) is a leading cause of cervical cancer. The National Cervical Screening Programme (NCSP) implemented HR-HPV primary screening to detect HR-HPV infections in the Netherlands in 2017. The choice of HR-HPV test (mRNA or DNA) used in screening programmes can impact resource use and costs, follow-up testing and referral for colposcopy.

A decision tree model was adapted from a previously published model in England to represent the current cervical screening flowchart in the Netherlands. The model estimates the impact on costs, the number of colposcopies, HR-HPV and cytology tests of using an mRNA assay compared to a DNA assay for a cohort aged 30 to 65 years. Results found adopting an mRNA HR-HPV test instead of a DNA test as part of the NCSP in the Netherlands, gave an estimated €1.8M in total cost savings annually. The results from the model are comparable to results for other countries including England, Sweden, Denmark, Canada, and France.

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Dombrowski C, Weston G, Adams E. Evaluating the benefits and costs of using an mRNA versus DNA HR-HPV assay in the National Cervical Screening Programme in the Netherlands. Poster presented at: EUROGIN International Multidisciplinary HPV Congress; 2021 May 30 – June 1; Virtual

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Modelling the impact of using a DNA compared to mRNA HPV assay as part of the cervical screening programmes in Sweden and Denmark

Nearly all cases of cervical cancer are caused by 14 high-risk human papillomavirus (HR-HPV) genotypes. Denmark and Sweden are assessing the structure of their cervical cancer screening programmes and implementing HR-HPV screening in certain populations. While both DNA and mRNA assays have similar sensitivity, mRNA assays have been shown to have higher specificity resulting in fewer false-positive results.

We adapted a decision tree model from a previously published study in England to explore how the type of assay used to detect HR HPV infections in a screening programme may impact costs, patient follow-up, and resource use. The results showed the use of mRNA tests in cervical screening for women in Sweden or Denmark instead of DNA testing would result in cost savings and a decrease in the number of unnecessary cytology tests, unnecessary recall HR-HPV tests and unnecessary colposcopies compared to HR-HPV DNA testing and can be used to inform the implementation of screening programmes with benefits for health services and women.

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Dombrowski C, Weston G, Adams E. Modelling the impact of using a DNA compared to mRNA HPV assay as part of the cervical screening programmes in Sweden and Denmark. Poster presented at: EUROGIN International Multidisciplinary HPV Congress; 2021 May 30 – June 1; Virtual

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Estimating the costs and benefits of HR-HPV assay choice in a theoretical HPV primary cervical screening algorithm in Ontario, Canada

Current cervical screening program guidelines for Ontario recommend cytology testing every 3 years for ages 25-70. Primary HR-HPV screening has been found to be more sensitive than primary cytology in detecting high-grade disease of the cervix. As Canadian provinces and territories move towards implementing primary HR-HPV screening in their cervical screening programs, how cervical screening is organized and implemented will need to be considered, including the choice of HR-HPV assay as the type of test influences costs and resource use.

A published decision tree model based on the Cervical Screening Programme (CSP) in England was adapted to simulate the primary HPV algorithm proposed by the Cervical Screening Guideline Working Group in Ontario. Results showed using mRNA tests instead of DNA tests could save over CAD $4 million annually, and avoid approximately 11,000 unnecessary colposcopies, 15,000 HPV tests and 40,000 cytology tests. Whilst the Ontario algorithm has not yet been agreed upon, this study shows that the choice of HPV assay is an important consideration within an HPV primary cervical screening program.

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Weston G, Steben M, Popadiuk C, Bentley J, Dombrowski C, Adams E. Estimating the costs and benefits of HR-HPV assay choice in a theoretical HPV primary cervical screening algorithm in Ontario, Canada. Poster presented at: EUROGIN International Multidisciplinary HPV Congress; 2021 May 30 – June 1; Virtual

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Evaluating the choice of HPV assay in the French cervical screening programme with a decision tree model

Persistent infection with high-risk human papillomavirus (HR-HPV) has been linked to precancerous lesions (cervical intraepithelial neoplasia (CIN)) which may progress to cervical cancer. Guidance was issued in 2020 in France to include the use of assays to detect HR-HPV infections in a national cervical screening programme.

A decision tree model was developed to evaluate the impact of using a similarly sensitive, but more specific, mRNA HR-HPV assay (Aptima HR-HPV assay) compared to a DNA HR-HPV test (cobas 4800 HPV assay) in the proposed cervical screening algorithm in France. Results showed using an mRNA assay could yield an estimated annual cost saving of €6.5 million and reduce the total number of colposcopies, HPV and cytology tests required. As mRNA and DNA assays have similar test sensitivity, true positives will not be missed, and total costs are reduced by eliminating unnecessary colposcopy referrals, HR-HPV and cytology tests.

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Dombrowski C, Weston G, Descamps P, Izopet J, Adams E. Evaluating the choice of HPV assay in the French cervical screening programme with a decision tree model. Poster presented at: EUROGIN International Multidisciplinary HPV Congress; 2021 May 30 – June 1; Virtual.

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Modelling the choice of high-risk human papillomavirus (HR-HPV) assay in the English cervical screening programme

Aquarius developed a decision tree model to compare the use of the Aptima mRNA HR-HPV assay to a DNA HR-HPV assay in the HPV primary screening algorithm in England. Robust results from the model demonstrate that using the mRNA HR-HPV assay is cost saving and avoids unnecessary HPV recall tests, cytology tests and colposcopies compared to using a DNA HR-HPV assay.

In England, women are invited for cervical cancer screening starting at age 25 and are recalled at regular intervals until age 64. In the HPV primary screening algorithm, cervical samples are tested first for HR-HPV. Positive HPV samples are then tested using liquid based cytology to identify abnormal cells.

Aquarius developed a cost consequence analysis decision tree taking the perspective of NHS England and modelling the HPV primary screening algorithm for one simulated cohort of 2,247,439 women aged 25-64 from baseline screen through recall visits. The model endpoint was discharge to routine recall, loss-to-follow up, or referral to colposcopy. A micro-costing approach was used to estimate costs for screening in England, using published data. Head-to-head comparison of mRNA to DNA tests at baseline and with follow-up was not available for the English population. Therefore, data from the HORIZON study in Denmark with similar positivity to that in England was used.

The model indicated that using an mRNA versus DNA assay in the HPV primary screening algorithm in England can save an estimated £15.4 million and require 28,009 fewer unnecessary colposcopies, 90,605 few HR-HPV tests and 253,477 fewer cytology tests.  Uncertainty and scenario analyses demonstrate cost and resource savings will almost certainly be achieved using the mRNA assay.

PublicationWeston G, Dombrowski C, Harvey MJ, et al Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation BMJ Open2020; 10:e031303. doi: 10.1136/bmjopen-2019-031303