Cost-effectiveness analysis of human papillomavirus vaccination in South Africa accounting for human immunodeficiency virus prevalence.

BACKGROUND: This study aims at evaluating the cost-effectiveness of a 2-dose schedule human papillomavirus (HPV) vaccination programme of HPV and human immunodeficiency virus (HIV) naïve 12-year-old girls, in addition to cervical cancer (CC) screening alone, in South Africa. The study aims to account for both the impact of the vaccine among girls who are HIV-positive (HIV+) as well as HIV-negative (HIV-) population. METHODS: A previously published Markov cohort model was adapted to assess the impact and cost-effectiveness of a HPV vaccination programme in girls aged 12 years (N = 527 900) using the AS04-adjuvanted HPV-16/18 vaccine from a public payer perspective. Two subpopulations were considered: HIV- and HIV+ women. Each population followed the HPV natural history with different transition probabilities. Model input data were obtained from the literature, local databases and Delphi panel. Costs and outcomes were discounted at 5 %. Extensive sensitivity analyses were conducted to assess the robustness of the evaluation. RESULTS: Implementation of the AS04-adjuvanted HPV-16/18 vaccine in combination with current cytological screening in South African girls could prevent up to 8 869 CC cases and 5 436 CC deaths over the lifetime of a single cohort. Without discounting, this HPV vaccine is dominant over screening alone; with discounting, the incremental cost-effectiveness ratio is ZAR 81 978 (South African Rand) per quality-adjusted life years (QALY) gained. HPV vaccination can be considered cost-effective based on World Health Organization (WHO) recommended threshold (3 x gross domestic product/capita = ZAR 200 293). In a scenario with a hypothetical targeted vaccination in a HIV+ subpopulation alone, the modelled outcomes suggest that HPV vaccination is still cost-effective, although the incremental cost-effectiveness ratio increases to ZAR 102 479. Results were sensitive to discount rate, vaccine efficacy, HIV incidence and mortality rates, and HPV-related disease transition probabilities. CONCLUSIONS: The AS04-adjuvanted HPV-16/18 vaccine can be considered cost-effective in a South African context although the cost-effectiveness is expected to be lower in the HIV+ subpopulation than in the overall female population. With improved access to HIV treatment, the HIV mortality and incidence rates are likely to be reduced, which could improve cost-effectiveness of the vaccination programme in South Africa.

Cost-effectiveness analysis of the bivalent compared with the quadrivalent human papillomavirus vaccines in Taiwan.

OBJECTIVE: To compare the epidemiological and economic impact of additional cross-protection against oncogenic human papillomavirus (HPV) types beyond 16/18 of the bivalent vaccine (BV) versus protection against nononcogenic HPV types 6/11 of the quadrivalent vaccine (QV) in Taiwan. METHODS: A lifetime Markov model calibrated to the Taiwanese setting simulated the natural history of low-risk (engendering cervical intraepithelial neoplasia [CIN] 1 and genital warts) and high-risk HPV (engendering CIN1, CIN2/3, and cervical cancer [CC]) infections, screening, and vaccination (100% coverage) for a cohort of 12-year-old girls (N = 153,000). Transition probabilities, costs, and utilities were estimated from published data and expert opinion. Vaccine efficacy was obtained from each vaccine's respective clinical trials. Price-parity and lifelong protection was assumed for both vaccines. The number of CIN lesions, CC cases, CC deaths and genital wart (GW) cases, and quality-adjusted life-years were estimated. Costs and outcomes (discounted at 3% and 1.5%, respectively) were compared from a payer's perspective. RESULTS: The model estimated that the BV led to an additional, undiscounted, 11,484 CIN1, 1,779 (+34.3% vs. QV) CIN2/3, 188 (+29.0% vs. QV) CC, and 69 (+29.0% vs. QV) CC deaths prevented compared with the QV, while the QV prevented 4,150 GW (+71%). This resulted in an additional 768 quality-adjusted life-years (QALY) and 11.6 million new Taiwan dollars costs saved for the BV versus the QV after discounting. CONCLUSION: Both vaccines have a different epidemiological impact with an increased number of CC-related lesions potentially prevented for the BV because of additional cross-protection. In the Taiwanese setting, HPV mass vaccination using the BV was estimated to dominate vaccination using the QV.

Cost-effectiveness analysis of prophylactic cervical cancer vaccination in Japanese women.

INTRODUCTION: The incidence of cervical cancer (CC) is high in Japan and is further increasing among women younger than 30 years. This burden could be reduced by the implementation of a CC vaccine, but its cost-effectiveness is unknown. METHODS: We quantified the clinical impact and assessed the cost-effectiveness of adding CC vaccination at age 12 to the current screening in place in Japan with a lifetime Markov model adapted to the Japanese setting. Transition probabilities and utility values were obtained from public databases. Direct costs for treatment and screening were estimated using Japanese medical fees. Annual costs and benefits were discounted at 3%. Sensitivity analyses were conducted on the age at vaccination, the vaccine characteristics, the discount rates, the proportion of human papillomavirus types 16/18 in cancer, and the screening coverage. RESULTS: Vaccinating a 12-year-old cohort was predicted to reduce CC incidence and deaths from CC by 73%. These clinical effects were associated with an incremental cost-effectiveness ratio of yen1.8 million per quality-adjusted life year gained. The incremental cost-effectiveness ratio of vaccinating all 10- to 45-year-old women was yen2.8 million per quality-adjusted life year, still below the threshold value. CONCLUSIONS: The implementation of a CC vaccination in Japan could reduce the CC burden in a very cost-effective manner for women up to 45 years.

A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females.

BACKGROUND: Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated. METHODS: A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3% discount rate on future costs and health effects. Conservative herd immunity effects were taken into account by estimated HPV incidence using a mathematical model parameterized by reported age-stratified sexual mixing data. Sensitivity analyses were performed to address parameter uncertainties. RESULTS: Vaccinating 12-year old females (n = 100,000) was estimated to prevent between 390-633 undiscounted cervical cancer cases (reduction of 47%-77%) and 168-275 undiscounted deaths (48%-78%) over their lifetime, depending on whether or not herd immunity and cross-protection against other oncogenic HPV types were included. Vaccination was estimated to cost $18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination. CONCLUSION: In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.

Cost-Utility of a Two-Dose Human Papillomavirus Vaccination Programme Added to Cervical Cancer Screening Compared with Cervical Cancer Screening Alone in Korea

Background: Cervical cancer is caused by the human papillomavirus and is a leading cause of cancer death among young Korean women. Current screening programmes could benefit from the addition of HPV vaccination into their schedule to help reduce disease burden. Two-dose vaccination schedules targeting HPV types 16 and 18, which are responsible for most cervical cancer cases, have recently been approved. Of the two available vaccines, AS04-adjuvanted HPV16/18 vaccine (AS04-HPV16/18v) provides greater protection against non-vaccine oncogenic HPV, while HPV-6/11/16/18 vaccine (4vHPVv) provides protection against genital warts. Methods: The health and economic consequences of introducing a two-dose HPV vaccination programme in 12-year-old girls together with screening were assessed in the Korean healthcare setting using a previously-published Markov model. Results: Compared with screening alone, AS04-HPV16/18v was cost-effective (incremental cost-effectiveness ratio below and within the Korean Won [KRW] 20-30 million treshold). When comparing the two vaccines, at 3% discount rate, AS04-HPV16/18v dominated 4vHPVv (i.e., provided 174 more quality-adjusted life-years (QALYs), 304 more life-years (LYs) and cost-savings of KRW 980 million). At a 5% discount rate, AS04-HPV16/18v provided comparable QALYs (albeit 5 fewer), 105 more LYs and cost-savings of KRW 292 million compared with 4vHPVv. Results were particularly sensitive to the discount rate used, as the health benefits of preventing cervical cancer are observed much later than those of preventing genital warts. Conclusion: For the Korean setting, HPV vaccination with a two-dose schedule is a cost-effective option, and AS04-HPV16/18v is likely to offer better health outcomes at a cost-saving compared with 4vHPVv.

Cost-Effectiveness Analysis of Human Papillomavirus Vaccination in Adolescent Girls in Taiwan

Objective: Three vaccines are available to Taiwanese young girls for cervical cancer (CC) prevention. Here we evaluate the cost-effectiveness of the two-dose (2D) AS04-adjuvanted HPV-16/18 vaccine (2D-AS04-HPV- 16/18v)+screening compared with a screening programme alone, with 2D human papillomavirus 6/11/16/18 vaccine (2D-4vHPVv)+screening, and with 2D/three-dose (3D) human papillomavirus 6/11/16/18/31/33/45/52/58 vaccine (9vHPVv)+screening, for Taiwan universal mass vaccination. Methods: A static Markov cohort model simulated the natural history of human papillomavirus (HPV) infection and CC screening for a 12-year-old cohort of Taiwanese girls (N=120,000). The model ran in 1-year cycles over the cohort's lifetime. Vaccine efficacy irrespective of HPV type was considered in the analysis for each vaccine. Input data were obtained from published literature, local databases, government reports and websites, and expert opinion. The analysis incorporated direct medical costs only, with an annual discount rate of 3.0%. The threshold was determined as 1 Gross Domestic Product per capita (New Taiwan dollar [NT$] 727,818; year 2016). Results: The 2D-AS04-HPV-16/18v+screening yielded 0.0365 quality-adjusted life year (QALY) gained at an additional cost of NT$ 5,770 per person compared with the screening programme alone. This resulted in an incremental cost-effectiveness ratio well below the threshold. Compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening, discounted results demonstrated additional QALYs gained at lower cost for 2D-AS04-HPV- 16/18v+screening, making it dominant over both 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening. Conclusions: Vaccinating Taiwanese girls with 2D-AS04-HPV-16/18v in addition to screening to prevent CC is cost-effective compared with using a screening programme alone and the dominant option compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening.

Resource Use and Cost of Treating Human Papillomavirus-Related Lesions in Japanese Women.

BACKGROUND: Human papillomavirus (HPV) infection is established as a necessary causal factor in several pathologies including cervical cancer (CC), which recorded over 11,000 new cases in 2011 in Japan. Nevertheless, cost burden data of human papillomavirus-related diseases in Japan are lacking. OBJECTIVES: To evaluate resource use and costs in women with HPV-related lesions. METHODS: A retrospective study using insurance claims databases was performed to assess the annual medical cost for suspected cervical intra-epithelial neoplasia (CIN)/CC, genital warts (GWs), CIN (all grades), and CC. Information on the treatment of GWs was obtained from the Claims Database developed by Japan Medical Data Center Co., Ltd. Information on CIN and CC was obtained from the Evidence-Based Medicine provider database developed by Medical Data Vision Co., Ltd. Databases cover about 1% of the Japanese population. Total annual cost in Japanese yen (¥) per patient in 2011 was calculated on the basis of resource used and unit costs from Japan medical insurance tariffs. RESULTS: Average annual costs were as follows: GWs, ¥34,424; suspected CIN/CC, ¥6,240; CIN 1, ¥17,484; CIN 2, ¥46,583; CIN 3, ¥166,227; and CC, ¥474,756. CONCLUSIONS: To our knowledge, this is the first observational study to estimate the annual medical costs of HPV-related diseases in Japan using real-world data collected in routine clinical practice. It could provide help in estimating the economic burden of HPV-related lesions in Japanese women.

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore.

INTRODUCTION: Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. METHODS: A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. RESULTS: Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. CONCLUSION: AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.

Comparative Cost-Effectiveness Analysis of Two Different Two-Dose Human Papillomavirus Vaccines in Malaysia

Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort's lifetime. Discounted total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV- 16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening, was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule.

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Estimation of the potential overall impact of human papillomavirus vaccination on cervical cancer cases and deaths.

BACKGROUND: Human papillomavirus (HPV) vaccination offers potential for primary prevention of HPV-related pre-cancers and cancers as demonstrated in clinical trials. Mathematical models have estimated the potential real-life impact of vaccination on the burden of cervical cancer (CC). However, these are restricted to evaluations in a limited number of countries. METHODS: Potential decline in CC cases and deaths with the AS04-adjuvanted HPV-16/18 vaccine of young girls naïve to HPV, was estimated at steady-state (vaccine coverage: 0-100%) based on clinical trial and country-specific incidence data. Data on vaccine efficacy were taken from the end of study PATRICIA trial of the AS04-adjuvanted HPV-16/18 vaccine. The numbers of cases and deaths due to HPV-16/18 were estimated and compared with those due to any HPV type to estimate the additional cases prevented. This difference estimates CC cases and deaths avoided due to protection against non-vaccine HPV types. Cost-offsets due to reductions in CC treatment were estimated for five countries (Brazil, Canada, Italy, Malaysia and South African Republic) using country-specific unit cost data. Additionally, cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3)-related burden (cases and treatment costs) prevented by vaccination were estimated for two countries (Italy and Malaysia). RESULTS: HPV vaccination could prevent a substantial number of CC cases and deaths in countries worldwide, with associated cost-offsets due to reduced CC treatment. Cross-protection increased the estimated potential number of CC cases and deaths prevented by 34 and 18% in Africa and Oceania, respectively. Moreover, vaccination could result in a substantial reduction in the number of CIN2/3 lesions and associated costs. CONCLUSION: HPV vaccination could reduce the burden of CC and precancerous lesions in countries worldwide, part of disease burden reduction being related to protection against non HPV-16/18 related types.

Incremental cost-effectiveness evaluation of vaccinating girls against cervical cancer pre- and post-sexual debut in Belgium.

BACKGROUND: Vaccination against human papillomavirus (HPV) to prevent cervical cancer (CC) primarily targets young girls before sexual debut and is cost-effective. We assessed whether vaccination with the HPV-16/18 AS04-adjuvanted vaccine added to screening remains cost-effective in females after sexual debut compared to screening alone in Belgium. The role of protection against non-HPV-16/18 was also investigated. METHODS: A published Markov cohort model was adapted to Belgium. The model replicated the natural history of HPV infection, the effects of screening, and vaccination. Vaccine efficacy (VE) included non-HPV-16/18 protection based on the PATRICIA clinical trial data. Pre- and post-HPV exposure VE were differentiated. Lifetime vaccine protection was assumed. Input data were obtained from literature review, national databases and a Delphi panel. Costing was from a healthcare payer perspective. Costs were discounted at 3% and effects at 1.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the number of lesions prevented with vaccination from age 12 to 40 was evaluated. The specific effect of non-HPV-16/18 protection was investigated. Univariate sensitivity analysis was performed on key variables. RESULTS: The model estimated that vaccinating a cohort of 100,000 girls at age 12 would prevent 646 CC cases over a lifetime (102 non-HPV-16/18) with an ICER of €9171/QALY. Vaccinating at age 26 would prevent 340 CC cases (40 non-HPV-16/18) with an ICER of €17,348/QALY and vaccinating at age 40 would prevent 146 CC cases (17 non-HPV-16/18) with an ICER of €42,847/QALY. The ICER remained under the highly cost-effective threshold (1×GDP/capita) until age 33 years and under the cost-effective threshold (3×GDP/capita) beyond age 40. CONCLUSION: Extending HPV vaccination to females post-sexual debut could lead to a substantial reduction in CC-related burden and would be cost-effective in Belgium.