Quality of included studies

The cost-effectiveness studies were assessed using the International Society for Pharmacoeconomics and Outcomes Research questionnaire to assess the relevance and credibility of modelling studies.⁽²²⁰⁾ Relevance was assessed on the grounds of the study population, characteristics of the intervention, outcomes measured and the overall study context. The credibility of the results was considered using criteria related to the design, validation and analysis methods, the quality of the data used, as well as how the results were reported and interpreted, and whether the authors had any conflicts of interest. All eight included studies were found to be of good quality. Reporting was generally adequate and considered to be fair and balanced.

5.1.5 Applicability of the evidence

Consistent evidence was found in all eight economic evaluation studies that using HPV testing as the primary screening test with cytology triage is cost-effective (or in some cases cost saving) compared with use of cytology as the primary screening test in the prevention of cervical cancer. There was no consistency however in what the optimal screening strategy should look like, with variation in the triaging options, screening frequency and age intervals between studies. This is consistent with the findings in the broader economic literature of HPV testing. In 2015, a systematic review of model-based cervical screening evaluations was published by Mendes et al.⁽¹⁵⁾ Although the primary objective of the review was to assess the type of models used in the economic evaluations, they did note that 15 of the 17 studies, that compared HPV to cytology-based testing as a primary screening test, considered HPV testing to be a cost-effective alternative.

In the 2009 Canadian study, none of the options considered reflect the current practice in Ireland of five-yearly screening for women aged between 45 and 60 years; the maximum screening interval assessed was three-yearly.⁽²¹⁷⁾ It is difficult to interpret how these findings would relate to the Irish screening service. The effect of strategies on vaccinated cohorts was also not considered.

In contrast to the other studies included in this review of the economic literature, the 2015 study by the Belgian HTA agency, KCE, evaluated a limited number of alternative strategies.⁽¹⁶⁴⁾ One of the key difficulties in applying the evidence from this study to Ireland is the cytology comparator. The cytology comparator used in

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151 the base case included a mix of both conventional cytology and LBC, representing current standard of care in Belgium, rather than LBC only as is used in Ireland. The costs of cytology were not readily available and a number of assumptions about the costs of the LBC test were made which may have led to an underestimate of the true LBC costs. Furthermore, there is currently no national screening programme in place in Belgium with organised screening only in the Flemish region, where there is a policy of three-yearly cytology screening for women aged 25 to 64 year. In other regions screening is opportunistic.

The 2013 Australian study included a large number of comparisons and considered the effects in both vaccinated and unvaccinated cohorts.⁽¹⁰⁾ The base case

comparator of two-yearly screening using conventional cytology for women aged 18 to 69 years is not however a strategy that would be considered in the Irish context.

The current screening programme in Ireland is considerably less intensive than the base case considered in the Australian study and comprises three-yearly screening from ages 25 to 44 years and then five-yearly screening from age 45 to 60 years.

The International Agency for Research on Cancer (IARC) recommended frequencies and age intervals of three-yearly screening from ages 25 to 49 years and five-yearly screening from age 50 to 64 years were evaluated in this report. These frequencies and intervals are also marginally more intensive than what is currently in place in Ireland and would result in approximately two or three additional screenings over each woman’s lifetime. For these reasons, the comparisons in this study are not reflective of the situation and comparators of interest in Ireland.

The 2014 study by Kitchener et al. for the National Institute for Health Research in the UK⁽¹⁷⁹⁾ included a large number of comparisons and the strategies considered were similar to those in place and being considered in Ireland. Similar to Ireland, the UK has an organised call-recall screening programme and universal HPV vaccination of 12 year old girls; uptake of both screening and vaccination are similar for the two countries. The discount rate for costs and health outcomes was 3.5%, which is lower than the 5% rate that is used in Ireland. Using a lower discount rate is likely to overestimate the benefits and costs, thus making it difficult to anticipate the effect this would have on the cost-effectiveness in the Irish settings. Also, similar to the Australian study the age ranges for the screening intervals are from 25 to 49 years and 50 to 64 years in contrast to the age ranges in Ireland of three-yearly from 25 to 44 years and then five-yearly from 45 to 60 years.

The 2012 Dutch study by Van Rosalmen et al.⁽²¹⁵⁾ was conducted from a societal perspective and used a discount rate of 3%. A HPV-vaccinated cohort was not considered in this model and it is unclear whether the current Irish strategy was considered, as although they adjusted the number of screening rounds, it is not

152 clear how this was done. For example, whether screening rounds were always

evenly distributed or whether, as is the case in Ireland, shorter intervals could be followed by longer intervals. Thus the results from this study are difficult to apply to the Irish setting.

The 2010 study by Vijayaraghavan et al. compared a number of LBC and HPV

screening options in the US.⁽²¹⁶⁾ The frequency of screening in all options considered was at most three-yearly, which is shorter than that currently used in Ireland. The effect of vaccination was not considered and the study was not considered in the context of an organised call-recall screening programme. The discount rate was not stated and it appears that discounting was not applied to the analysis. Also it was difficult to rule out bias due to conflicts of interest as all authors received fees from one of the test manufacturers. For these reasons the results from this study are not applicable to the Irish setting.

The 2016 New Zealand study⁽²¹⁸⁾ considered alternative screening strategies similar to those being considered in Ireland. However, the current screening programme in Ireland is less intensive than the base case considered in the New Zealand study, which comprises three-yearly liquid-based cytology with HPV triage (triage applied only to women over 30) for women aged 20 to 69 years. Combined with the lower discount rate used (3.5% versus 5% in Ireland), the findings of the study may not be applicable to the Irish setting.

There has been no published cost-effectiveness literature on HPV testing as a primary screening strategy in Ireland. In 2015, Agapova et al.⁽²²⁴⁾ considered the long-term costs of introducing HPV testing in the surveillance of women post treatment for cervical cancer in Ireland. Co-testing with HPV and LBC was found to be cost saving over a 12-year period, compared with LBC only.

5.1.6 Conclusions

Few economic evaluations comparing primary HPV screening with primary LBC screening for prevention of cervical cancer have been published. While consistent evidence was found that cervical screening programmes using HPV testing as the primary screening test are cost-effective and potentially cost saving when compared with programmes using cytology as the primary screening test, it is not possible to determine the optimal screening strategy from the available literature. The identified economic evaluations are quite heterogeneous in terms of the strategies considered, the inclusion of vaccinated cohorts and discount rates used. The variation in

strategies considered is particularly important, as no study that considered a

strategy which reflects the current cervical screening programme in place in Ireland

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153 was found. Ireland has already adopted LBC testing and has a less intensive

screening programme than many of the alternatives considered in the literature.

Given differences in healthcare delivery costs and screening programmes considered, it was not possible to determine the optimal screening strategy for Ireland based on the available literature. A de novo economic evaluation was therefore required to inform decision-making.