Francesco Saverio Mennini

Health and economic impact associated with a quadrivalent HPV vaccine in Italy

OBJECTIVE The aim of this study was to determine the health impact and cost-effectiveness of introducing a human papillomavirus (HPV) vaccination programme with a quadrivalent vaccine alongside the existing cervical cancer screening programme in comparison to the current context in Italy. METHODS A US Markov model was adapted to the Italian context, assuming under base case 80% vaccine coverage rate, lifetime duration of protection in a cohort of girls aged 12 years and discount rates of 1.5% and 3% for health benefits and costs, respectively, and estimating direct medical costs. RESULTS The HPV vaccination in association with the current screening programme would allow to avoid 1432 cases of cervical cancer (-63.3%) and 513 deaths (-63.4%) compared to screening only, with an incremental cost-effectiveness ratio (ICER) of 9569 euros per additional quality-adjusted life-year (QALY) gained. The sensitivity analysis highlighted that this model was robust to all parameters presenting uncertainties as the ICERs ranged from 2,781 euros to 48,122 euros per QALY gained. CONCLUSION This study showed that HPV vaccination in adolescent girls would be a beneficial and cost-effective public health programme in Italy.

Economic burden of human papillomavirus-related diseases in Italy

Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

Towards the eradication of HPV infection through universal specific vaccination

BackgroundThe Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies.DiscussionA panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations’ intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men.SummaryThe reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

Improving care through health economics analyses: cost of illness and headache

The impact of headache disorders is a problem of enormous proportions, both for individual and society. The medical literature tried to assess its effects on individuals, by examining prevalence, distribution, attack frequency and duration, and headache-related disability, as well as effects on society, looking at the socio-economic burden of headache disorders [Rasmussen (Cephalalgia 19:20–23, 1999)]; [Lanteri-Minet et al. (Pain 102:143–149, 2003)]. The issue of costs represents an important problem too, concerning both direct and indirect costs. Direct costs concern mainly expenses for drugs. Migraine has a considerable impact on functional capacity, resulting in disrupted work and social activities: many migraineurs do not seek medical attention because they have not been accurately diagnosed by a physician or do not use prescribed medication [Solomon and Price (Pharmacoeconomics 11:1–10, 1997)]. Indirect costs associated with reduced productivity represent a substantial proportion of the total cost of migraine as well. Migraine has a major impact on the working sector of the population, and therefore, determining the indirect costs outweighs the direct costs. This study will explain the notion of cost of illness, examining how it could be applied in such a framework. Then, an overview of the studies aimed at measuring direct and indirect costs of migraine and headache disorders will be carried out, later shifting on to the relationship between costs and quality of life for people affected by headache disorders. Finally, a brief review on advantages of new pharmaceuticals and preventive treatments for migraine for patients and society will outline improvements in the context of cost-effectiveness and cost-utility analysis.

Anti-HPV vaccination: A review of recent economic data for Italy

The total cost of HPV-related diseases accounts for euro 200-250 million of which euro 210 million is absorbed by the prevention and treatment of precancerous lesions and cervical cancer. Although both available HPV vaccines are below the threshold value for economic convenience (euro 9,569 and euro 26,361 per QALY-gained for the quadrivalent and bivalent vaccines, respectively), at this point in time long-term economic models developed for Italy seem to indicate the quadrivalent vaccine as the most cost-effective option. Recent publications by official bodies, including the World Health Organization and the Supervisory Authority for Public Contracts in Italy, recommend that the decision-making process be based on both the quality of goods and services as well as the best achievable price.

Public health value of universal HPV vaccination

BACKGROUND The story of Human Papillomavirus vaccination demands reflection not only for its public health impact on the prophylactic management of HPV disease, but also for its relevant economic and social outcomes. Greater than ever data confirm the efficacy and support the urge for effective vaccination plans for both genders before sexual debut. METHODS A review of previous experience in gender-restricted vaccination programs has demonstrated a lower effectiveness. Limiting vaccination to women might increase the psychological burden on women by confirming a perceived inequality between genders; and even if all women were immunized, the HPV chain of transmission would still be maintained through men. RESULTS The cost-effectiveness of including boys into HPV vaccination programs should be re-assessed in view of the progressive drop of the economic burden of HPV-related diseases in men and women due to universal vaccination. The cost of the remarkable increase in anal and oropharyngeal HPV driven cancers in both sexes has been grossly underestimated or ignored. CONCLUSIONS Steps must be taken by relevant bodies to achieve the target of universal vaccination. The analysis of HPV vaccinations clinical effectiveness vs. economic efficacy are supportive of the economic sustainability of vaccination programs both in women and men. In Europe, these achievements demand urgent attention to the social equity for both genders in healthcare. There is sufficient ethical, scientific, strategic and economic evidence to urge the European Community to develop and implement a coordinated and comprehensive strategy aimed at both genders and geographically balanced, to eradicate cervical cancer and other diseases caused by HPV in Europe. Policymakers must take into consideration effective vaccination programs in the prevention of cancers.

Hospital costs incurred by the Italian National Health Service for invasive cervical cancer

METHODS A longitudinal, retrospective, cohort study was designed to assess the mean treatment cost of invasive cervical cancer, cross-linking clinical and administrative databases. The study was performed from the Italian NHS perspective. Costs were estimated using DRG charges. All patients with histological diagnosis of invasive cervical cancer admitted to Gynecologic Oncology centres of the Catholic University of the Sacred Heart between 2000 and 2007 were enrolled. RESULTS Overall, 351 patients (212 with LACC and 139 with ECC) were eligible for analysis. The mean direct medical cost by patient was € 22,200 ± 21,600 with a significantly higher burden for LACC compared with ECC patients (€ 28,696 ± 24,874 versus € 12,329 ± 8,726). Radical surgery accounted for € 6,851 ± 1,406, and € 7,709 ± 3,710 in ECC and LACC group, respectively; the resulting difference achieved a statistical significance. The extent of disease, disease progression/recurrence, and length of hospitalization confirmed their independent role as cost predictive factors. CONCLUSIONS The combined use of administrative and clinical databases allowed a feasible assessment of the mean cost induced by the invasive cervical cancer. Management of LACC patients was associated with higher costs due to the utilization of several therapeutic strategies and more frequent appearance of disease progression/recurrence.

Novel Health Economic Evaluation of a Vaccination Strategy to Prevent HPV-related Diseases The BEST Study

Background:The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. Methods:A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. Results:The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to &OV0556;12,013, &OV0556;13,232, and &OV0556;15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8–6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient=&OV0556;12.6). Conclusions:This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study

BACKGROUND Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence

SUMMARY In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs’ results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16–26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%–99·8%). Bridging efficacy was demonstrated for males and females aged 9–15 years and males aged 16–26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.