Quantifying the broader economic consequences of quadrivalent human papillomavirus (HPV) vaccination in Germany applying a government perspective framework.

HPV infections can cause substantial burden in females and males as it is associated with several genital cancers, in addition to genital warts. Traditional economic evaluations often focus on quantifying cost-effectiveness, however, it is increasingly recognized that vaccinations may generate broader benefits not captured in cost-effectiveness analysis. Τhe aim of this study was to evaluate the broader economic consequences associated with HPV vaccination in males and females and to conduct a lifetime cost-benefit analysis of investing in universal vaccination in Germany from the perspective of government. Methodologies from generational accounting, human capital and health economics were combined to estimate the broader economic consequences of HPV vaccination including the fiscal impact for the government. A cohort model was developed simulating the medical costs and average lifetime fiscal transfers between the government and 12-year-old immunized and non-immunized males and females. To estimate tax revenue attributed to vaccination-related changes in morbidity and mortality, direct and indirect tax rates were linked to differences in age- and gender-specific earnings. Based on HPV vaccination costs, the base case cost-benefit analysis demonstrated that investing 1 in universal HPV vaccination could yield 1.7 in gross tax revenue over the lifetime of the cohorts. After taking into consideration the governmental transfers, universal HPV vaccination in Germany could result in incremental positive net discounted taxes (i.e. tax revenue-transfers) from 62 million for the German government. The vaccination of males and females with the quadrivalent HPV vaccine is likely to have positive effects on public finances.

The intangible benefits of vaccination - what is the true economic value of vaccination?

Previous economic evaluations of new vaccines largely focussed on a narrow set of benefit categories, including primarily health gains and disease-related medical cost-savings, which probably resulted in underestimates of the true value of these vaccines. Other economic benefits of vaccines could be considered to assess the full economic value of vaccination, such as, for example, impact of the human papillomavirus vaccine on women's fertility through the decrease in precancerous lesions and, therefore, in the number of diagnostic and treatment interventions, which can be associated with an increased risk of subsequent pregnancy complications. Vaccines' impact on resource allocation at hospital level or on antimicrobial resistance, such as pneumococcal conjugate vaccines that have substantially reduced infections due to antimicrobial non-susceptible strains, thereby rendering the residual disease easier to treat, are other examples of intangible benefits of vaccination. These benefits are generally not considered in economic evaluations because they may not be immediately visible and are difficult to quantify. However, they should be taken into consideration in health technology assessments to enable those responsible for healthcare policies to make well-informed decisions on vaccination.

Vaccination: the cornerstone of an efficient healthcare system.

Vaccination has made an important contribution to the decreased incidence of numerous infectious diseases and associated mortality. In 2013, it was estimated that 103 million cases of childhood diseases in the United States had been prevented by the use of vaccines since 1924. These health effects translate into positive economic results, as vaccination can provide significant savings by avoiding the direct and indirect costs associated with treating the disease and possible long-term disability. A recent US study estimated that every dollar spent on childhood vaccination could save US$3 from a payer perspective and US$10 from a societal perspective. The first vaccines set a high standard from a public health 'return on investment' perspective, because they are highly cost-saving. Today, however, where only a few healthcare interventions are considered to be cost-saving, the challenge that decision-makers typically face is to identify such healthcare interventions that are deemed cost-effective, that is, provide extra benefit at a reasonable extra cost. Some of the newer vaccines provide a solution to some of today's important health issues, such as cervical cancers with human papillomavirus vaccines, or debilitating diseases with herpes zoster vaccines. These recent, more expensive vaccines have been shown to be cost-effective in several economic analyses. Overall, vaccination can still be regarded as one of the most cost-effective healthcare interventions.

Annual cost of hospitalization, inpatient rehabilitation, and sick leave for head and neck cancers in Germany.

BACKGROUND: Data on the economic burden of head and neck cancers (HNCs) in Germany is scarce. About 16%-28% of these cancers are associated with human papillomavirus (HPV) infection. Therefore, the study reported here aimed to assess the annual costs of HPV-related HNCs incurred by hospitalization, inpatient rehabilitation, and sick leave in Germany in 2008. METHODS: A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to HNCs in 2008 were analyzed. Associated numbers of HNC hospitalizations, health care resource use, and costs were identified and extracted using the International Classification of Diseases, tenth revision (ICD-10; World Health Organization, Geneva, 1990) codes C01-C06, C09-C14, and C32 as the main diagnoses. Resources were valued with German official prices in 2008 euros (€). The annual costs of HPV-related HNCs were estimated based on the percentage of HNCs likely to be attributable to HPV infection. RESULTS: In 2008, there were 63,857 hospitalizations, 4898 inpatient rehabilitations, and 17,494 sick leaves due to HNCs, representing costs of €365.78 million. The estimated annual costs associated with HPV-related HNCs were €78.22 million, mainly attributed to males (80%). Direct costs accounted for 84% (80% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 16% of HPV-related HNC costs. CONCLUSION: The economic burden of HPV-related HNCs in Germany in 2008 has been underestimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, as far as we are aware, this study is the first analysis to investigate the economic burden of HNCs in Germany. The estimated annual costs of HPV-related HNCs contribute to a significant economic burden in Germany and should be considered when assessing the health and economic benefits of HPV vaccination in both sexes.

Annual cost of hospitalization, inpatient rehabilitation and sick leave of anal cancer in Germany.

OBJECTIVE: Literature on the economic burden of anal cancer in Germany is scarce. About 84% of these cancers are associated with human papillomavirus infection. This study, therefore, aimed to assess the annual costs of human papillomavirus-related anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in 2008 in Germany. METHODS: A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to anal cancer in 2008 were analyzed. Associated numbers of anal cancer hospitalizations, healthcare resource use, and costs were identified and extracted using the ICD-10 code C21 as the main diagnosis. The annual cost of human papillomavirus-related anal cancer was estimated based on the percentage of anal cancer likely to be attributable to human papillomavirus. RESULTS: In 2008, there were 5774 hospitalizations (39% males, 61% females), 517 inpatient rehabilitations, and 897 sick leaves due to anal cancer representing costs of €34.11 million. The estimated annual costs associated with human papillomavirus-related anal cancer were €28.72 million, mainly attributed to females (62%). Direct costs accounted for 90% (86% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 10% of human papillomavirus-related costs. CONCLUSIONS: The economic burden of human papillomavirus-related anal cancer in 2008 in Germany is under-estimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, this study is the first analysis to investigate the economic burden of anal cancer in Germany. The estimated annual costs of human papillomavirus-related anal cancer contribute to a significant economic burden in Germany and should be considered when assessing health and economic benefits of human papillomavirus vaccination in both genders.

Cost-effectiveness of vaccination with a quadrivalent HPV vaccine in Germany using a dynamic transmission model.

INTRODUCTION: Persistent infections with human papillomavirus (HPV) are a necessary cause of cervical cancer and are responsible for important morbidity in men and women. Since 2007, HPV vaccination has been recommended and funded for all girls aged 12 to 17 in Germany. A previously published cost-effectiveness analysis, using a static model, showed that a quadrivalent HPV vaccination programme for 12-year-old girls in Germany would be cost effective. Here we present the results from a dynamic transmission model that can be used to evaluate the impact and cost-effectiveness of different vaccination schemas. METHODS: We adapted a HPV dynamic transmission model, which has been used in other countries, to the German context. The model was used to compare a cervical cancer screening only strategy with a strategy of combining vaccination of females aged 12-17 years old and cervical cancer screening, based on the current recommendations in Germany. In addition, the impact of increasing vaccination coverage in this cohort of females aged 12-17 years old was evaluated in sensitivity analysis. RESULTS: The results from this analysis show that the current quadrivalent HPV vaccination programme of females ages 12 to 17 in Germany is cost-effective with an ICER of 5,525€/QALY (quality adjusted life year). The incremental cost-effectiveness ratio (ICER) increased to 10,293€/QALY when the vaccine effects on HPV6/11 diseases were excluded. At steady state, the model predicted that vaccinating girls aged 12 to 17 could reduce the number of HPV 6/11/16/18-related cervical cancers by 65% and genital warts among women and men by 70% and 48%, respectively. The impact on HPV-related disease incidence and costs avoided would occur relatively soon after initiating the vaccine programme, with much of the early impact being due to the prevention of HPV6/11-related genital warts. CONCLUSIONS: These results show that the current quadrivalent HPV vaccination and cervical cancer screening programmes in Germany will substantially reduce the incidence of cervical cancer, cervical intraepithelial neoplasia (CIN) and genital warts. The evaluated vaccination strategies were all found to be cost-effective. Future analyses should include more HPV-related diseases.

Head and neck cancers in France: an analysis of the hospital medical information system (PMSI) database.

BACKGROUND: With 16,005 new cases and 5,406 related deaths in 2005, France is particularly concerned by Head and Neck (H&N) cancers. In addition to tobacco and alcohol, Human Papillomavirus (HPV) has been reported as a risk factor for H&N cancers. The literature on the burden of these cancers in Europe is scarce. This study was performed to assess the medical and economical burden of hospitalisations for H&N cancers in France. METHODS: The French national hospital database (PMSI), in which admissions to public and private hospitals are recorded, was retrospectively analysed to assess the annual number of patients hospitalised for H&N cancers and associated hospital costs from the healthcare payer perspective. ICD-10 codes (16 codes classified as oral cavity, oropharynx, pharynx, salivary glands and larynx) were used to extract admissions for these cancers. Hospital stays, chemotherapy and radiotherapy sessions were extracted to assess patients' management. Costs of admissions were obtained from French official tariffs. RESULTS: In 2007, there were 36 268 patients hospitalised for H&N cancers, of whom 81% were men, corresponding to 60 200 hospital stays and 287 846 sessions of chemo- or radio-therapy. Oropharynx cancer was the most frequent (28% of patients), followed by oral cavity cancer (25% of patients). The peak of frequency was observed in the 55-59 years age group. Patients were mainly treated in medicine (48%) and surgery (23%) units. Mean annual cost per patient ranged from €2,764 to €7,673 leading to a total hospital cost of €323 millions in 2007 (including hospitalization and expensive drugs). With 26% of H&N cancers attributable to HPV infections, 9 430 patients were hospitalized due to HPV-related H&N cancers, representing €138 million in 2007. CONCLUSION: Even without taking into account the rehabilitation costs, the hospital burden of H&N cancers is considerable.

Vulvar and vaginal cancers and dysplasia in France--an analysis of the hospital medical information system (PMSI) database.

OBJECTIVE: Literature on the epidemiology of vulvar and vaginal cancers is scarce. The incidence of these diseases seems to be increasing. It has been reported that about 40% of vulvar and 70% of vaginal cancers may be linked to human papillomavirus (HPV). This study aimed to assess the medical burden associated with hospitalizations and management of vulvar and vaginal cancers and dysplasia (VIN and VaIN) in France. STUDY DESIGN: A retrospective analysis using the French national hospital database (PMSI) was performed to assess the annual number of patients hospitalized for vulvar and vaginal cancers and VIN/VaIN, based on hospital admissions in 2006. Data for all stays and chemotherapy/radiotherapy sessions were extracted. SAE database (Statistiques annuelles des établissements de santé) was used to take into account patients who had radiotherapy sessions performed in the private sector which are not reported in the PMSI. RESULTS: In 2006, 1237 and 623 patients were hospitalized for vulvar cancer and VIN, respectively. There were also 728 and 244 patients hospitalized for vaginal cancer and VaIN, respectively. Overall, about 35% of all patients were hospitalized in the private setting. For all lesions except vaginal cancer, surgery was the most common type of management. For vaginal cancer, medical care was the most prevalent (52%), followed by surgery (31%). CONCLUSION: The burden of hospitalizations due to vulvar and vaginal cancers is substantial. Further research is needed to assess the outpatient burden due to these diseases especially for precancerous dysplasia which may be mostly managed in an outpatient setting.

Cost-effectiveness evaluation of a quadrivalent human papillomavirus vaccine in Belgium.

BACKGROUND: The introduction of a quadrivalent human papillomavirus (HPV; types 6, 11, 16, 18) vaccine is expected to significantly reduce the burden of cervical cancer, cervical intraepithelial neoplasia (CIN), genital warts and other HPV-related diseases. OBJECTIVE: To determine the cost effectiveness of providing a quadrivalent (6,11,16,18) HPV vaccine programme in adolescent females aged 12 years in addition to the existing cervical cancer screening programme in Belgium. METHODS: A Markov state-transition model was developed for the Belgian context in order to evaluate the long-term impact of vaccinating a cohort of girls aged 12 years alongside the existing screening programme. Women were followed until the age of 85 years. A vaccine that would prevent 100% of diseases associated with HPV-6, -11, -16 and -18, with lifetime duration of efficacy, 80% coverage, in conjunction with current screening, was compared with screening alone. For this analysis, 35% of cases of CIN-1, 55% of CIN-2/3, 75% of cervical cancer and 90% of genital warts were considered to be attributable to HPV-6, -11, -16 or -18. The model estimated lifetime risks and total lifetime healthcare costs, survival and QALYs for cervical cancer, CIN and genital warts. Outcomes validation was applied. Model outcomes also included incremental costs per life-year gained and incremental costs per QALY gained. The analysis was conducted from the perspective of the Belgian healthcare payer, and costs were in year 2006 values. RESULTS: The model estimated a reduction in the lifetime risk of cervical cancer from 0.94% to 0.34%, therefore preventing 362 cases of cervical cancer and 131 related deaths in a cohort of 60,000 girls aged 12 years in Belgium. The base-case scenario suggests quadrivalent HPV vaccination in addition to current cervical screening in Belgium to be cost effective at euro 10,546 per QALY. This is within the accepted range of cost-effective interventions in Europe. This cost effectiveness is maintained for different parameter assumptions in the sensitivity analysis, with the exception of very high discount rates for costs and medical benefits, but, even in the worst case, ratios were still less than euro 50,000 per QALY. Even when a separate scenario modelled the requirement for a booster vaccination to sustain a lifetime duration of protection, the results remained cost effective at eruo 17,388 per QALY. CONCLUSIONS: Vaccination with a quadrivalent HPV vaccine appears to be a cost-effective public health intervention in conjunction with the existing screening programme in Belgium. The additional costs of introducing vaccination to the established screening programme would be offset by the potential savings from not having to treat the diseases caused by HPV-6, -11, -16 or -18.

Epidemiology and costs of screening and management of precancerous lesions of the cervix in Spain.

OBJECTIVE: Oncogenic human papillomaviruses (HPVs) are essential causes of cervical cancer. Screening prevents cancer by detecting precancerous lesions (cervical intraepithelial neoplasia, CIN). Our aim was to assess the annual number of Pap smears and CIN diagnoses in Spain and to estimate associated management costs. MATERIALS AND METHODS: A 1-year retrospective cross-sectional study was conducted among 65 gynecologists from public primary health care centers in 6 autonomous regions in Spain. We documented the total number of Pap smears performed and the management of women with CIN. Data on health care resource use related to CIN management for 2 years after diagnosis were collected and combined with unit costs to assess the mean cost per patient. We extrapolated to the general female Spanish population to estimate the total cost of screening and CIN management from the third-party payer's perspective. RESULTS: In our study sample, 3.5% of routine Pap smears were abnormal. We estimated that 7.6 million Pap smears are performed annually in Spain, at a cost of 622 million euro (US$987). Furthermore, 40,530 women are annually diagnosed with CIN 1, 26,243 with CIN 2, and 28,423 with CIN 3. The mean cost of CIN management per patient was 1,115 euro for CIN 1, 1,626 euro for CIN 2, and 2,090 euro for CIN 3. The total cost of CIN management was estimated at 147 million euro (US$233). CONCLUSIONS: This study shows that the costs of screening and management of CIN represent a heavy burden to the public health system in Spain.

Epidemiology and cost of treatment of genital warts in Spain.

BACKGROUND: Genital warts (GW) are common and increasing in young people. Ninety percent of GW are due to Human Papillomavirus (HPV) types 6 and 11. The objective of this study was to assess the epidemiology and management costs associated with GW in Spain. METHODS: A 1-year (2005) retrospective observational study was performed among a sample of gynaecologists, dermatologists and urologists in six autonomous regions in Spain. Men and women with newly diagnosed, recurrent or resistant GW were included. We estimated the incidence (new and recurrent cases) and prevalence (also including resistant cases) of GW. Healthcare resource use were collected and combined with unit costs to assess the mean cost of GW management per patient. These figures were extrapolated to the 14- to 64-year-old Spanish population to estimate the total cost of GW management from the Third Party Payer (TPP) and societal perspectives. RESULTS: The overall annual incidence of GW was estimated at 160.4 cases per 100,000. Overall prevalence was calculated as 182.1 cases per 100,000, corresponding to 56 446 GW cases annually (14- to 64-year-old population). The mean management cost was 833 euros and 1056 euro per patient from the TPP and societal perspective, respectively. The overall annual cost was estimated at 47 million euros and 59.6 million euros, from the TPP and societal perspective, respectively. CONCLUSION: This study provides a first overview of the burden of GW in Spain. A quadrivalent HPV vaccine that prevents HPV 6, 11, 16, 18 related diseases will have the potential to significantly decrease the socio-economic burden associated with GW in Spain.

Cost-effectiveness analysis of the introduction of a quadrivalent human papillomavirus vaccine in France.

OBJECTIVES: A vaccine to prevent diseases due to human papillomavirus (HPV) types 6, 11, 16, and 18 is now available in France. The objective of this study was to assess the health and economic impact in France of implementing a quadrivalent HPV vaccine alongside existing screening practices versus screening alone. METHODS: A Markov model of the natural history of HPV infection incorporating screening and vaccination, was adapted to the French context. A vaccine that would prevent 100 percent of HPV 6, 11, 16, and 18-associated diseases, with lifetime duration and 80 percent coverage, given to girls at age 14 in conjunction with current screening was compared with screening alone. Results were analyzed from both a direct healthcare cost perspective (DCP) and a third-party payer perspective (TPP). Indirect costs such as productivity loss were not taken into account in this analysis. RESULTS: The incremental cost per life-year gained from vaccination was euro12,429 (TPP) and euro20,455 (DCP). The incremental cost per quality-adjusted life-year (QALY) for the introduction of HPV vaccination alongside the French cervical cancer screening program was euro8,408 (TPP) and euro13,809 (DCP). Sensitivity analyses demonstrated that cost-effectiveness was stable, but was most sensitive to the discount rate used for costs and benefits. CONCLUSIONS: Considering the commonly accepted threshold of euro50,000 per QALY, these analyses support the fact that adding a quadrivalent HPV vaccine to the current screening program in France is a cost-effective strategy for reducing the burden of cervical cancer, precancerous lesions, and genital warts caused by HPV types 6, 11, 16, and 18.

Economic burden associated with the management of cervical cancer, cervical dysplasia and genital warts in Belgium.

OBJECTIVE: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium. METHOD: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective. RESULTS: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of euro9,716, the total annual cost of CC is euro6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of euro1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of euro2.53 million (HCPP). CONCLUSION: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.

[Invasive cervical cancer treatment costs in France]. / Coût de la prise en charge du cancer invasif du col de l'utérus en France.

The objective of this study was to estimate the direct costs of invasive cervical cancer (ICC) management to the French national health insurance system the 1st year after ICC diagnosis. A retrospective survey was conducted in three centres in 2005, including 42 patients admitted for ICC between 2001-2003. Medical records were examined for data relating to treatments and to determine the management costs. To estimate the annual cost of ICC management in France, data were extrapolated to the general population. The number of new ICC cases in France was estimated at 3,247 in 2003. The mean hospitalisation cost increased with ICC severity at diagnosis: 9,164 euros for stage I, 15,999 euros for stage II, 22,697 euros for stage III, and 26,886 euros for stage IV. The annual cost associated with the medical management of ICC patients was estimated at 43,862,125 euros (sensitivity range 32,973,461 euros-54,748,422 euros) corresponding to a mean patient cost of 13,509 euros. Recent HPV vaccination studies have shown 100 % for a quadrivalent (6,11,16,18) HPV vaccine against HPV-induced carcinoma in situ (FIGO stage 0/CIN3), a precursor lesion that may develop into ICC. Thus, it is expected that this vaccine will significantly reduce the socio-economic burden associated with this disease.