Human papillomavirus (HPV)-induced malignancies represent the second most common type of cancer in women worldwide.1
In Italy, more than 3000–3500 new cases of cervical cancer (which corresponds to an age-standardised rate of incidence of between 7.7 and 8.1 cases per 100 000 women) are diagnosed annually,2
and approximately 1200 women die from this disease every year.2
Overall, the economic burden to the Italian National Health Service that is caused by cervical HPV-related pathologies is considerable, with the cost estimated to lie in the range €200–250 million per year.4
A programme of screening for cervical cancer has been implemented in Italy since 1996 to reduce the incidence of cervical cancer and its associated mortality rate. Women aged between 25 and 64 years are invited for screening for cervical cancer every 3 years, with the aim of achieving the early detection and treatment of precancerous cervical lesions (cervical intraepithelial neoplasia (CIN)) and preventing the onset of invasive cervical cancer.6
In early 2007, a new tool became available to reduce the incidence of HPV-related malignancies: the vaccine in its bivalent and quadrivalent form. The cost–effectiveness of immunisation against HPV had been previously demonstrated by a large number of modelling studies.7–13
In one such study that was carried out in Italy, the authors assessed the cost–effectiveness of a programme of quadrivalent vaccination for a single cohort of 12-year-old girls.14
In their model, the current programme of screening (including the management of HPV-related pathologies) was considered as a comparative case. The results of their study suggested that the introduction of a programme of vaccination using a quadrivalent HPV vaccine alongside the current programme of screening for cervical cancer in Italy would produce an incremental cost–effectiveness ratio of €12 303 per life year gained and €9569 per quality-adjusted life year gained. An economic assessment of the bivalent vaccine reported a cost of €26 361 per quality-adjusted life year gained,15
which provided further evidence that vaccination against HPV is currently significantly below the threshold value of €30 000–45 000 that is used commonly to determine ‘value for money’ in health interventions.16
The difference in the economic evaluation of the two anti-HPV vaccines were mostly determined by the quadrivalent's efficacy in preventing anogenital warts, a non-life-threatening HPV-induced disease.
More favourable economic results were obtained using predictive models that were based on a quadrivalent multicohort strategy of vaccination (three to four cohorts).18
When a multicohort strategy of vaccination is adopted, a larger proportion of the female population aged between 12 and 25 years can be vaccinated in a shorter period of time (5–8 years) and an early reduction of costs can be expected. A multicohort programme of vaccination using the quadrivalent vaccine was associated with a total saving of approximately €132 million, as a result of a reduction in the numbers of low-grade and high-grade cervical lesions, anogenital warts and invasive cervical cancers ().21
Projected outcomes averted by means of the quadrivalent vaccine and expected reductions in expenditure
In July 2007, a decree issued by the State-Regions Conference granted access to quadrivalent vaccination against HPV, which should mandatorily be both free of charge and promoted actively, at least in the cohort of girls aged 12 years, with the progressive achievement of a rate of coverage of 95% in the next 5 years. The decree was resolving the uncertainty related to the choice of the vaccine (quadrivalent) and the priority of cohort to be immunised (12-year-old girls), but the actual modalities of implementation of the immunisation campaign were delegated to individual regions, under the constraint that the incremental cost of the anti-HPV vaccination would be funded within a budget previously allocated to healthcare. In order to maximise the net benefits or utilities to public health that can be derived from a proposed decision, it is essential to allocate resources as efficiently as possible, in full compliance with the universal principles of equity of access to treatment.22
The policy makers of the Basilicata region, in the south of Italy, became concerned about the potential issues of equality and allocative efficiency of resources raised by the choices at hand.
A downsize of the current screening programme could potentially increase the risk of HPV-related malignancies, in the light of the lack of information about the impact of immunisation on the coverage and frequency of screening. In time, women vaccinated in the multicohort immunisation programme would enter the age group 25–64 years and thus should still be considered eligible for screening. The option to reduce the resources dedicated to screening would therefore be unethical and, ultimately, it would be likely to have an adverse effect on the women's welfare.
On the other hand, the implementation of a quadrivalent multicohort strategy of vaccination in the region could provide clinical and economic benefits 5–8 years earlier than would be expected with the 12-year-old single-cohort strategy made mandatory by the national guidelines. It should be considered, though, that the validity of cost–effective studies is strongly dependent on the accuracy of complex models, based on hundreds of assumptions often derived by sparse sources. In spite of the prescriptive nature of health economic outcomes, they cannot completely resolve the uncertainty at the time of the investment decision, determined by the lack of information on population-wide efficacy of the anti-HPV vaccine in the long term. Moreover, a multicohort vaccination strategy would increase the complexity of the immunisation programme, whose rate of implementation represents an unknown variable itself in the simpler one-cohort model.
After a number of consultations, the healthcare policy makers of the Basilicata region made the following implementation choices:
- To adopt a four-cohort immunisation strategy targeting women who were born in 1983, 1990, 1993 and 1997. Data on vaccination coverage rates by cohort are reported in .
Data on vaccination rates provided by the Basilicata region and included in the bound optimisation model
- To maintain the coverage rate (women aged between 25 and 64 years) and the frequency (3 years) of the screening programme.
- To allocate a maximum allowable budget for 2007/2008 to finance both the screening and the immunisation programmes of €2.5 million.
These constraints were added ex-ante to the choice of the quadrivalent anti-HPV vaccine and the long-term target coverage for the 12-year-old cohort of girls (95% in 5 years), which were mandated by Law (Ministry of Health) at national level.
The objective of this study was to support the healthcare management of the Basilicata region to achieve the allocative efficiency of the allowable budget assigned to anti-HPV screening and quadrivalent immunisation programmes. In general terms, the allocative efficiency of a budget between two healthcare programmes is reached when the population welfare is maximised.23
As this particular budget was earmarked to prevent HPV-related malignancies, its allocative efficiency would be reached when the number of HPV-related events is minimised, given three additional conditions: no change in the frequency and coverage of the current screening programme, a multicohort modality of implementation of the new immunisation programme and the achievement of the target coverage required by the national guidelines for the cohort of 12-year-old girls. A further condition required by allocative efficiency is that the allowable budget is entirely spent. To date, no studies have examined specifically the level of allocative efficiency of resources assigned to programmes of vaccination against HPV. In order to provide quantitative guidelines relevant to managerial decision, the main objective of the study was further divided into two complementary outcomes:
- Objective ex-ante: the determination of the most efficient allocation of resources between the screening and the multicohort quadrivalent immunisation programme, given the constraints discussed above.
- Objective ex-post: the assessment of the allocative efficiency actually achieved by the screening and the quadrivalent immunisation programmes 12 months after the beginning of its implementation (July 2007).
The research outcomes were strictly dependent upon the given constraints stipulated ex-ante by political choices made at regional level, namely the choice of the quadrivalent anti-HPV vaccine, the multicohort immunisation strategy and the frequency and coverage of screening. It was beyond the scope of this paper to determine and compare the allocative efficiency of alternative scenarios based on different constraints (eg, the choice of the bivalent anti-HPV vaccine, a single-cohort immunisation strategy or a different frequency and coverage of the screening programme). The sensitivity analysis reported in the discussion of the results provides an indication of the sensitivity of allocation efficiency to the main parameters taken into consideration, including the allowable budget, the size of the female population eligible for immunisation and/or screening, the annual cost of immunisation and screening and their relative efficacy in preventing HPV-related diseases, such as abnormal Pap smears, precancerous cervical lesions (CIN1, CIN2–3), invasive cervical cancer and anogenital warts.