The purpose of this study has been to evaluate and compare options for introducing LBC and/or HPV testing into cervical cancer screening programmes. All the screening options have been chosen to reflect those that have been previously proposed or evaluated. However, this is the only study that has evaluated all screening options in combination.
Under baseline assumptions, the cost–effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, the marginal cost of LBC does affect outcomes. If we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. The cost–effectiveness of primary HPV testing with LBC appears less sensitive to changes in the LBC marginal cost, but this is because in our one-way sensitivity analysis, variability in cost is only associated with the cytology laboratory costs and not HPV costs. Combined primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options. However, both the primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime.
Adding LBC to the current programme is predicted to match or improve effectiveness under the full range of assumptions used for sensitivity analysis, and, likewise, if it was further modified by adding HPV testing as a triage for mild or borderline smear abnormalities. Changing to the combined smear and HPV testing option and raising the screening interval to 5 years, could improve effectiveness, similarly if the programme is changed to primary HPV testing. However, under these options, the predicted impact is less robust to the assumptions we have made: their effectiveness being very sensitive to the relative diagnostic accuracy of the HPV test in relation to cytology, HPV prevalence and whether there is any consistent difficulty in detecting HPV infections in some women.
Since a modelling approach has been used, there has been scope for analysing a wide range of options. Several different scenarios have been analysed to allow for the uncertainty regarding the model parameters. This uncertainty not only reflects the range of estimates reported in the scientific literature, but also the imprecise knowledge regarding the natural history and age-related prevalence of HPV infections and cervical precancers both now and in the future. Evaluating different scenarios has enabled us to investigate how robust predicted outcomes are to changes in model assumptions, to identify areas of uncertainty that have a large influence on outcome, and identify circumstances under which particular options are less favourable.
The costs used in the model are based on best estimates currently available, although no account has been taken of the training and transfer costs associated with moving from the current screening programme to one including LBC and/or HPV testing and neither have transportation costs for HPV samples been included. It is recognised that the prospective resource utilisation data come from a relatively small number of practices in the UK and the cost data for LBC are based largely on assumption.
Previous studies have analysed the impact of LBC on cervical screening programmes (McCrory et al, 1999
; Payne et al, 2000
; Kim et al, 2002
; Moss et al, 2002
). All are based wholly, or partly on mathematical modelling, but none have investigated the whole range of options in this study together. All studies conclude that introducing LBC within a primary smear testing programme could be cost-effective with (Kim et al 2002
), or without (McCrory et al, 1999
; Payne et al, 2000
; Moss et al, 2002
) HPV testing as a triage. They all predict improvements in effectiveness, but the impact on cost depends on the assumed marginal cost for the new technology. Of these, the lowest marginal cost was calculated by the UK Cervical Screening Pilot Site study, which is the only one to predict overall cost savings. This study also found that LBC reduces the number of inadequate smears by about 80% yet has little impact on test sensitivity. Three studies have investigated combined smear and HPV testing and HPV testing alone as primary screening methods, but without LBC (Van Ballegooijen et al, 1997
; Cuzick et al, 1999b
; Mandelblatt et al, 2002
). The latter of these only compared 2- and 3-year screening intervals, yet found a combined test to be feasible if extended to an older age group. The two former studies, as with this study, found combined screening options at 3- and 5-year intervals to be more costly yet more effective than 3-year smear testing, much of the extra cost being due to screening and surveillance. Also, similar to our own findings, the relative impact of primary HPV testing was less robust to different versions of their model and so difficult to determine.
The mathematical model is a tool for making the best use of the available information, yet the results cannot be treated as definitive. There are further factors that have not been investigated which could influence the outcomes. Women are assumed to be either always compliant or not, and no account has been taken of how compliance, and hence effectiveness, could be improved by reducing the number of tests a woman is required to attend, for example, by extending the screening interval, combining smear and HPV tests and reducing the number of inadequate smears. The performance of screening tests has also assumed to be the same for all ages, although there is evidence that cytological accuracy declines among older women (Mandelblatt et al, 1991
). There is much controversy over appropriate discount rates, and incremental cost–effectiveness ratios can only be interpreted against the rates that are chosen. However, alternative views of discounting have little impact on how different options stand in relation to each other.
The aim of this study was to evaluate screening in the context of the UK, and care would need to be taken before translating its results to other settings. International comparisons of cost–effectiveness are hampered by differences in health systems, resource and cost structures, chosen comparators and recommended methods for evaluating technologies. Guidelines on appropriate discount rates differ between countries; in the United States for example, the current recommendations are 3% for both costs and life years (Weinstein et al, 1996
). Perhaps more importantly, at 9–10%, the proportion of smears classified as inadequate is particularly high in the UK in comparison to other developed countries, and, as a result, any reduction in this proportion due to the introduction of liquid-based technology may be of greater benefit than elsewhere.
Since cost and life years saved are not the only outcomes of importance, other measures could come to the fore in the decision making process. In terms of the psychological impact on women, high false positive rates for referral to colposcopy may count against the acceptability of primary HPV testing and combined primary smear and HPV testing. This may also be an unnecessary use of expensive resources. The HART study, however, suggested that this problem could be overcome in primary HPV testing by annual monitoring of women who are HPV positive with borderline or negative cytology (Cuzick et al, 2003
). Also, for women being screened, lower numbers of inadequate smears would be desirable, and evidence suggests such reductions occur with LBC without compromising sensitivity (Moss et al, 2002