Age-Based Programs for Vaccination against HPV

Background:  The risk of infection with human papillomavirus (HPV) increases with age. Answering the question of which age groups are appropriate to target for catch-up vaccination with the newly licensed quadrivalent HPV vaccine (types 6/11/16/18) will be important for developing vaccine policy recommendations.
Objectives:  To assess the value of varying female HPV vaccination strategies by specific age groups of a catch-up program in the United States.
Methods:  The authors used previously published mathematical population dynamic model and cost-utility analysis to evaluate the public health impact and cost-effectiveness of alternative quadrivalent HPV (6/11/16/18) vaccination strategies. The model simulates heterosexual transmission of HPV infection and occurrence of cervical intraepithelial neoplasia (CIN), cervical cancer, and external genital warts in an age-structured population stratified by sex and sexual activity groups. The cost-utility analysis estimates the cost of vaccination, screening, diagnosis, and treatment of HPV diseases, and quality-adjusted survival.
Results:  Compared with the current screening practices, vaccinating girls and women ages 12 to 24 years was the most effective strategy, reducing the number of HPV6/11/16/18-related genital warts, CIN grades 2 and 3, and cervical cancer cases among women in the next 25 years by 3,049,285, 1,399,935, and 30,021; respectively. The incremental cost-effectiveness ratio of this strategy when compared with vaccinating girls and women ages 12 to 19 years was $10,986 per quality-adjusted life-year gained.
Conclusion:  Relative to other commonly accepted health-care programs, vaccinating girls and women ages 12 to 24 years appears cost-effective.     

Impact of vaccinating boys and men against HPV in the United States

We assessed the public health impact and value of vaccinating boys and men with the quadrivalent HPV vaccine in the United States. We used mathematical population models, accounting for both the direct and indirect protective effects of vaccination. Inputs for the models were obtained from public data sources, published literature, and analyses of clinical trial data. Compared with a program of vaccinating girls and women only, including boys and men 9–26 years of age would further decrease the cumulative mean number of genital wart cases, cervical intraepithelial neoplasia 2/3 cases, cancer cases, and cancer deaths by 5,146,000, 708,000, 116,000, and 40,000, respectively, within 100 years. The mean cost-effectiveness ratio (2008 US $) of this strategy was $25,700 (range: 13,600–48,800) per QALY gained if vaccination protects against all HPV 6/11/16/18-associated diseases, and $69,000 (range: 37,700–152,300)/QALY if it only protects against diseases currently in the vaccine indication. Vaccinating boys and men age 9–26 against all HPV 6/11/16/18-associated diseases provides substantial public health benefits and is cost-effective at commonly cited thresholds.     

Public health impact and cost-effectiveness of a nine-valent gender-neutral HPV vaccination program in France

ObjectivesIn France, 9-valent HPV vaccination is recommended routinely for 11–14-years-old girls and as catch-up for 15–19-years-old girls. Recently, recommendation for gender-neutral vaccination (GNV) has been approved. The objectives of the study were to assess the public health impact and cost-effectiveness of a 9-valent GNV compared with girls-only vaccination program (GOV).MethodsA published HPV disease transmission dynamic model accounting for herd protection effects with a 100-year time horizon was adapted and calibrated to French data. Epidemiological and economic outcomes included disease cases averted and quality-adjusted life years (QALY). Costs and incremental cost-effectiveness ratio (ICER) were measured in 2018 Euros (€). A coverage rate of 26.2% among girls and boys was assumed for the GNV program based on the current female coverage rate in France. The base case included genital warts, cervical, vulvar, vaginal, and anal cancers. Scenario analyses included all HPV-related diseases and considered higher vaccination coverage rate (60%). Deterministic sensitivity analyses on key inputs were performed.ResultsOver 100 years, GNV resulted in an additional reduction of 9,519 and 3,037 cervical cancer cases and deaths; 6,901 and 1,166 additional anal cancer cases and deaths; and a reduction of additional 1,284,077 genital warts compared with current GOV and an ICER of 24,763€/QALY. When including all HPV-related diseases, the ICER was 15,184€/QALY. At a higher coverage rate (60%), GNV would prevent 17,430 and 4,334 additional anogenital cancer cases and deaths and over two million genital warts compared with GOV with an ICER of 40,401€/QALY. Results were sensitive to a higher discount rate (6% versus 4%) and a shorter duration of protection (20 years versus lifetime).ConclusionsIn France, GNV has a significant impact in terms of public health benefits and may be considered cost-effective compared with GOV at low and high coverage rates.     

Cost-effectiveness of human papillomavirus vaccination in Germany

Background

The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model.

Methods

Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys.

Results

From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls.

Conclusions

Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.

     

Cost–effectiveness of the prophylactic HPV vaccine: An application to the Netherlands taking non-cervical cancers and cross-protection into account

Despite an effective screening programme, 600–700 women are still diagnosed with cervical cancer in the Netherlands each year. In 2009 a prophylactic vaccine against HPV-type 16 and 18 was implemented in the national immunisation programme to decrease the incidence of cervical cancer. There is evidence that infections with several oncogenic HPV types other than the vaccine types 16 and 18 are also prevented by vaccination, also known as cross-protection. Besides cervical cancer, HPV can also cause cancers at other sites such as the oropharynx, vulva, vagina and the anus/anal area. In this study we estimated the maximum health and economic benefits of vaccinating 12-year old girls against infection with HPV, taking cross-protection and non-cervical cancers into account. In the base-case, we found an incremental cost ratio (ICER) of €5815 per quality adjusted life year (QALY). Robustness of this result was examined in sensitivity analysis. The ICER proved to be most sensitive to vaccine price, discounting rates, costs of cervical cancer and to variation in the disutility of cervical cancer.     

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage

BackgroundEstonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening.MethodsA Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN 1–3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88 years (up to 100 years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%.ResultsVaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367–21,711, €5142–21,800 and €4563–18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage.ConclusionVaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used.     

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.     

Cost-effectiveness of a tetravalent human papillomavirus vaccine in Germany

Aim  Clinical trials have demonstrated the efficacy of the tetravalent human papillomavirus (HPV) vaccination in the prevention of cervical cancer and genital warts associated with HPV types 6, 11, 16 and 18. We used an empirically calibrated Markov cohort model of the natural history of HPV to assess the cost-effectiveness of the vaccine administered to 12-year-old girls alongside existing cervical screening programmes in Germany. Subjects and methods  The model estimated cervical cancer (CC), cervical intraepithelial neoplasia (CIN) and genital wart lifetime risks and total lifetime health care costs, life years gained and quality-adjusted life years (QALY) gained. The analysis was conducted from the perspective of the German health care payer. Results  In the base case (considering a lifetime duration of protection and 100% efficacy) it was estimated that 2,835 cervical cancer cases and 679 deaths could be prevented among a cohort of 400,000, at an incremental cost per QALY gained of 10,530 €. A total of 120 girls needed to be vaccinated to prevent 1 case of CC. Cost-effectiveness is sensitive to a duration of protection of less than 20 years and to the discount rate for costs and benefits. Conclusion  A policy of vaccinating adolescent girls has been recommended by the German Standing Committee on Vaccinations. This study has demonstrated that such a policy is cost-effective based on thresholds of cost-effectiveness that apply in Germany.     

Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy

Background

In Italy HPV vaccination with the quadrivalent vaccine (Gardasil^®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9^®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11.

Methods

A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered.

Conclusion

The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective.

Results

Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.

     

Cost-effectiveness of a potential vaccine for human papillomavirus

Human papillomavirus (HPV) infection, usually a sexually transmitted disease, is a risk factor for cervical cancer. Given the substantial disease and death associated with HPV and cervical cancer, development of a prophylactic HPV vaccine is a public health priority. We evaluated the cost-effectiveness of vaccinating adolescent girls for high-risk HPV infections relative to current practice. A vaccine with a 75% probability of immunity against high-risk HPV infection resulted in a life-expectancy gain of 2.8 days or 4.0 quality-adjusted life days at a cost of $246 relative to current practice (incremental cost effectiveness of $22,755/quality-adjusted life year [QALY]). If all 12-year-old girls currently living in the United States were vaccinated, >1,300 deaths from cervical cancer would be averted during their lifetimes. Vaccination of girls against high-risk HPV is relatively cost effective even when vaccine efficacy is low. If the vaccine efficacy rate is 35%, the cost effectiveness increases to $52,398/QALY. Although gains in life expectancy may be modest at the individual level, population benefits are substantial.     

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.     

Cost-effectiveness and equity impacts of three HPV vaccination programmes for school-aged girls in New Zealand

Background

As with many high-income countries, vaccination coverage against human papilloma virus (HPV) infection is not high in New Zealand (NZ) at 47% in school-aged girls for three doses. We estimate the health gains, net-cost and cost-effectiveness of the currently implemented HPV national vaccination programme of vaccination dispersed across schools and primary care, and two alternatives: school-based only (assumed coverage as per Australia: 73%), and mandatory school-based vaccination but with opt-out permitted (coverage 93%). We also generate estimates by social group (sex, ethnic and deprivation group).

Methods

A Markov macro-simulation model was developed for 12-year-old girls and boys in 2011, with future health states of: cervical cancer, pre-cancer (CIN I–III), genital warts, and three other HPV-related cancers (oropharyngeal, anal, vulvar cancer). In each state health sector costs, including additional health sector costs from extra life, and quality-adjusted life years (QALYs) were accumulated.

Results

The current HPV vaccination programme has an estimated cost-effectiveness of NZ$18,800/QALY gained (about US$9700/QALY gained using the OECD's purchasing power parities; 95% UI: US$6900 to $33,700) compared to the status quo in NZ prior to 2008 (no vaccination, screening alone). The incremental cost-effectiveness ratio (ICER) of an intensive school-based only programme of girls, compared to the current situation, was US$33,000/QALY gained. Mandatory vaccination appeared least cost-effective (ICER compared to school-based of US$117,000/QALY gained, but with wide 95% uncertainty limits from $56,000 to $220,000). All interventions generated more QALYs per 12-year-old for Māori (indigenous population) and people living in deprived areas (range 5–25% greater QALYs gained).

Interpretation

A more intensive school-only vaccination programme seems warranted. Reductions in vaccine price will greatly improve cost-effectiveness of all options, possibly making a law for mandatory vaccination optimal from a health sector perspective. All interventions could reduce ethnic and socioeconomic disparities in HPV-related disease.     

Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective

BackgroundWe investigated the effectiveness and cost-effectiveness of a targeted human papillomavirus (HPV) vaccination program for young (15–26) men who have sex with men (MSM).MethodsWe developed a compartmental model to project HPV epidemic trajectories in MSM for three vaccination scenarios: a boys program, a targeted program for young MSM only and the combination of the two over 2017–2036. We assessed the gain in quality-adjusted-life-years (QALY) in 190,000 Australian MSM.ResultsA targeted program for young MSM only that achieved 20% coverage per year, without a boys program, will prevent 49,283 (31,253–71,500) cases of anogenital warts, 191 (88–319) person-years living with anal cancer through 2017–2036 but will only stablise anal cancer incidence. In contrast, a boys program will prevent 82,056 (52,100–117,164) cases of anogenital warts, 447 (204–725) person-years living with anal cancers through 2017–2036 and see major declines in anal cancer. This can reduce 90% low- and high-risk HPV in young MSM by 2024 and 2032, respectively, but will require vaccinating ≥84% of boys. Adding a targeted program for young MSM to an existing boys program would prevent an additional 14,912 (8479–21,803) anogenital wart and 91 (42–152) person-years living with anal cancer. In combination with a boys’ program, a catch-up program for young MSM will cost an additional $AUD 6788 ($4628–11,989) per QALY gained, but delaying its implementation reduced its cost-effectiveness.ConclusionsA boys program that achieved coverage of about 84% will result in a 90% reduction in HPV. A targeted program for young MSM is cost-effective if timely implemented.     

Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom

Many countries are considering vaccination against human papillomavirus (HPV). However, the long-term impact of vaccination is difficult to predict due to uncertainty about the prevalence of HPV infection, pattern of sexual partnerships, progression of cervical neoplasias, accuracy of screening as well as the duration of infectiousness and immunity. Dynamic models of human papillomavirus (HPV) transmission were developed to describe the infection spread and development of cervical neoplasia, cervical cancer (squamous cell and adenocarcinoma) and anogenital warts. Using different combinations of assumptions, 9900 scenarios were created. Each scenario was then fitted to epidemiological data and the best-fitting scenarios used to predict the impact of vaccination. Results suggest that vaccinating 12-year-old girls at 80% coverage will result in a 38–82% reduction in cervical cancer incidence and 44–100% reduction in anogenital warts incidence after 60 years of an ongoing vaccination programme if vaccine protection lasts 20 years on average. The marginal benefit of vaccinating boys depends on the degree of protection achieved by vaccinating girls.     

Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States

Estimates of the direct medical costs attributable to human papillomavirus (HPV) can help to quantify the economic burden of HPV and to illustrate the potential benefits of HPV vaccination. The purpose of this report was to update the estimated annual direct medical costs of the prevention and treatment of HPV-associated disease in the United States, for all HPV types. We included the costs of cervical cancer screening and follow-up and the treatment costs of the following HPV-associated health outcomes: cervical cancer, other anogenital cancers (anal, vaginal, vulvar and penile), oropharyngeal cancer, genital warts, and recurrent respiratory papillomatosis (RRP). We obtained updated incidence and cost estimates from the literature. The overall annual direct medical cost burden of preventing and treating HPV-associated disease was estimated to be $8.0 billion (2010 U.S. dollars). Of this total cost, about $6.6 billion (82.3%) was for routine cervical cancer screening and follow-up, $1.0 billion (12.0%) was for cancer (including $0.4 billion for cervical cancer and $0.3 billion for oropharyngeal cancer), $0.3 billion (3.6%) was for genital warts, and $0.2 billion (2.1%) was for RRP.     

Cost-effectiveness of quadrivalent human papillomavirus (HPV) vaccination in Mexico: a transmission dynamic model-based evaluation

We examined the potential health outcomes and cost-effectiveness of quadrivalent human papillomavirus (HPV) 6/11/16/18 vaccination strategies in the Mexican population using a multi-HPV type dynamic transmission model. Assuming similar cervical screening practices, with or without vaccination, we examined the incremental cost-effectiveness of vaccination strategies for 12 year-old females, with or without male vaccination, and temporary age 12-24 catch-up vaccination for females or both sexes. The most effective strategy therein was vaccination of 12-year-olds, plus a temporary 12-24-year-old catch-up program covering both sexes; whereby HPV 6/11/16/18-related cervical cancer, high-grade cervical precancer, and genital wart incidence was reduced by 84-98% during year 50 following vaccine introduction. Incremental cost-effectiveness ratios in the primary analyses ranged from approximately 3000 dollars (U.S.) per quality-adjusted life year (QALY) gained for female vaccination strategies to approximately 16000 dollars /QALY for adding male vaccination with catch-up.     

Mothers’ preferences and willingness to pay for vaccinating daughters against human papillomavirus

A choice-format, conjoint-analysis survey was developed and fielded to estimate how features of human papillomavirus (HPV) vaccines affect mothers’ perceived benefit and stated vaccine uptake for daughters. Data were collected from a national sample of 307 U.S. mothers of girls aged 13–17 years who had not yet received an HPV vaccine. Preferences for four features of HPV vaccines were evaluated: protection against cervical cancer, protection against genital warts, duration of protection, and cost. We estimate that mean maximum willingness-to-pay (WTP)—an economic measure of the total benefits to consumers—for current HPV vaccine technology ranges between $560 and $660. All vaccine features were statistically significant determinants of WTP and uptake. Mothers were willing to pay $238 more for a vaccine that provides 90% protection for genital warts relative to a vaccine that provides no protection against warts. WTP for lifetime protection vs. 10 years protection was $245. Mothers strongly valued greater cervical cancer efficacy, with 100% protection against cervical cancers the most desired feature overall. Adding a second HPV vaccine choice to U.S. consumers’ alternatives is predicted to increase stated uptake by 16%. Several features were significantly associated with stated choices and uptake: age of mother, race/ethnicity, household income, and concern about HPV risks. These findings provide new data on how HPV vaccines are viewed and valued by mothers, and how uptake may change in the context of evolving vaccine technology and as new data are reported on duration and efficacy.     

The clinical benefit and cost-effectiveness of human papillomavirus vaccination for adult women in the Netherlands

Background

The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17-25 years in 2010.

Methods

The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status.

Results

In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17-25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status.

Conclusion

The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17-25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.     

The cost-effectiveness of male HPV vaccination in the United States

Introduction

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States.

Methods

We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers.

Results

The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated.

Conclusions

HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population.     

Cost-effectiveness analysis of quadrivalent and nonavalent human papillomavirus vaccines in Ethiopia

BackgroundIn Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (?6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia.MethodA static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered.ResultsAt a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita.ConclusionCompared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15.