Evaluating human papillomavirus vaccination programs

Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of 14,583 dollars per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2% at an incremental cost-effectiveness ratio of 442,039 dollars/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination.     

Model for assessing human papillomavirus vaccination strategies

We present a transmission dynamic model that can assess the epidemiologic consequences and cost-effectiveness of alternative strategies of administering a prophylactic quadrivalent (types 6/11/16/18) human papillomavirus (HPV) vaccine in a setting of organized cervical cancer screening in the United States. Compared with current practice, vaccinating girls before the age of 12 years would reduce the incidence of genital warts (83%) and cervical cancer (78%) due to HPV 6/11/16/18. The incremental cost-effectiveness ratio (ICER) of augmenting this strategy with a temporary catch-up program for 12- to 24-year-olds was US $4,666 per quality-adjusted life year (QALY) gained. Relative to other commonly accepted healthcare programs, vaccinating girls and women appears cost-effective. Including men and boys in the program was the most effective strategy, reducing the incidence of genital warts, cervical intraepithelial neoplasia, and cervical cancer by 97%, 91%, and 91%, respectively. The ICER of this strategy was $45,056 per QALY.     

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.     

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands

In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy.     

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.     

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.     

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.     

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.     

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: A transmission-dynamic modeling study

Background

The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions.

Methods

We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs ($CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations.

Results

Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, $95/dose), using the quadrivalent and bivalent vaccines is estimated to cost $15,528 [12,056;19,140] and $20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is $32 [17;46] (using a $40,000/QALY-gained threshold). Results were most sensitive to discounting, time-horizon, differences in durations of protection and anogenital warts burden.

Conclusions

Vaccinating pre-adolescent girls against HPV is predicted to be highly cost-effective. If equally priced, the quadrivalent is the most economically desirable vaccine. However, ultimately, the most cost-effective HPV vaccine will be determined by their relative price.     

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.     

The potential cost-effectiveness of adding a human papillomavirus vaccine to the cervical cancer screening programme in South Africa

This study was designed to answer the question of whether a cervical cancer prevention programme that incorporates a human papillomavirus (HPV) vaccine is potentially more cost-effective than the current strategy of screening alone in South Africa. We developed a static Markov state transition model to describe the screening and management of cervical cancer within the South African context. The incremental cost-effectiveness ratio of adding HPV vaccination to the screening programme ranged from US $1078 to 1460 per quality-adjusted life year (QALY) gained and US$3320–4495 per life year saved, mainly depending on whether the study was viewed from a health service or a societal perspective. Using discounted costs and benefits, the threshold analysis indicated that a vaccine price reduction of 60% or more would make the vaccine plus screening strategy more cost-effective than the screening only approach. To address the issue of affordability and cost-effectiveness, the pharmaceutical companies need to make a commitment to price reductions.     

Cost-effectiveness of human papillomavirus vaccination in the United States

We describe a simplified model, based on the current economic and health effects of human papillomavirus (HPV), to estimate the cost-effectiveness of HPV vaccination of 12-year-old girls in the United States. Under base-case parameter values, the estimated cost per quality-adjusted life year gained by vaccination in the context of current cervical cancer screening practices in the United States ranged from $3,906 to $14,723 (2005 US dollars), depending on factors such as whether herd immunity effects were assumed; the types of HPV targeted by the vaccine; and whether the benefits of preventing anal, vaginal, vulvar, and oropharyngeal cancers were included. The results of our simplified model were consistent with published studies based on more complex models when key assumptions were similar. This consistency is reassuring because models of varying complexity will be essential tools for policy makers in the development of optimal HPV vaccination strategies.     

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.     

Mothers' preferences and willingness to pay for HPV vaccines in Vinh Long Province, Vietnam

About 530,000 women develop cervical cancer worldwide and 275,000 die from the disease each year. Eighty percent of these deaths occur in developing countries. In Vietnam, cervical cancer has recently emerged as the most common type of cancer in women, and there are no national screening programs for cervical cancer. Since 2009, two different human papillomavirus (HPV) vaccines have been licensed for use in Vietnam, but access to these vaccines is generally limited to people who live in urban areas. Studies have shown that HPV vaccination may be cost-effective in cervical cancer prevention in Vietnam, depending on vaccination costs. Given that current HPV vaccines are expensive and public health funding for supporting a rapid introduction of the vaccine is limited, expanding and sustaining access to the HPV vaccine may require alternative financing mechanisms, such as fees-based immunization services. A conjoint analysis study was conducted with mothers of girls 9-17 years of age in Vinh Long Province in Vietnam to estimate the mothers' demand for HPV vaccines for their daughters and to measure the tradeoffs between vaccine fees and vaccine uptake. The results suggest that the demand for HPV vaccines was high, increased with vaccine effectiveness and duration of effectiveness, and decreased with vaccine cost. Vaccine effectiveness was the most important vaccine attribute to these mothers, followed by duration of effectiveness. The predicted probability of respondents buying an HPV vaccine that was 70% effective for 10 years varied by the price, ranging from 30% when the vaccine price was $353 per course, to 68% when the vaccine cost $6 per course. As expected, demand and predicted purchase probability were higher among groups with higher socioeconomic status.     

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.     

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.

     

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: A transmission-dynamic modelling study

Background

Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada.

Methods

We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost.

Findings

Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900–24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated.

Interpretation

Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.     

Determining the “Health Benefit Basket” of the Statutory Health Insurance scheme in Germany

We compared findings from recent studies modelling the cost-effectiveness of screening for cervical cancer using human papillomavirus (HPV) testing and alternative strategies. Data were standardized to facilitate comparison of costs per life year or costs per QALY gained in six studies. Absolute changes in costs, life years and QALYs for each strategy were normalized to a comparison with no screening. Costs were standardized to US$ in 2000 values. Most models assume screening starts at age 18 or 20 years. Assumed prevalence of HPV ranges from 10% for those aged 18 years to 20% for those aged 20–25 years and drops substantially after age 30. All except one model assume sensitivity to LSIL of 83% or higher. Two models distinguish the increasing specificity of HPV testing in older age groups (up to 95% for LSIL in women aged 55 years or older). All the models include consultation costs as well as screening and treatment costs, but costs for follow-up diagnosis and treatment vary considerably. Two models also include patient time costs. Despite these differences all strategies involving HPV testing have cost per quality-adjusted life-year (QALY) ratios in the range of $12,400–$16,600. Costs per life year vary more widely, the highest being $19,246 (annual screening with liquid cytology and HPV). However, excluding strategies using liquid cytology, the highest costs per life year for a strategy including HPV testing are under $14,000 (simultaneous conventional cytology and HPV every two years). The cost per life year for HPV testing alone triennially is lower than for Pap smear testing alone biennially. Costs per QALY are generally lower than costs per life year (given the reported modelling assumptions and settings). Even with inclusion of patient costs, no strategies involving HPV testing cost more than $16,600 per QALY. Adoption of the ACOG guidelines to include HPV testing with cytology as a screening option for women aged 30 years or older therefore appears to be cost-effective.     

Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries

The risk of dying from cervical cancer is disproportionately borne by women in developing countries. Two new vaccines are highly effective in preventing HPV 16,18 infection, responsible for approximately 70% of cervical cancer, in girls not previously infected. The GAVI Alliance (GAVI) provides technical assistance and financial support for immunization in the world's poorest countries. Using population-based and epidemiologic data for 72 GAVI-eligible countries we estimate averted cervical cancer cases and deaths, disability-adjusted years of life (DALYs) averted and incremental cost-effectiveness ratios (I$/DALY averted) associated with HPV 16,18 vaccination of young adolescent girls. In addition to vaccine coverage and efficacy, relative and absolute cancer reduction depended on underlying incidence, proportion attributable to HPV types 16 and 18, population age-structure and competing mortality. With 70% coverage, mean reduction in the lifetime risk of cancer is below 40% in some countries (e.g., Nigeria, Ghana) and above 50% in others (e.g., India, Uganda, Kenya). At I$10 per vaccinated girl (approximately $2.00 per dose assuming three doses, plus wastage, administration, program support) vaccination was cost-effective in all countries using a per capita GDP threshold; for 49 of 72 countries, the cost per DALY averted was less than I$100 and for 59 countries, it was less than I$200. Taking into account country-specific assumptions (per capita GNI, DPT3 coverage, percentage of girls who are enrolled in fifth grade) for the year of introduction, percent coverage achieved in the first year, and years to maximum coverage, a 10-year modeled scenario prevented the future deaths of approximately 2 million women vaccinated as adolescents. Despite favorable cost-effectiveness, assessment of financial costs raised concerns about affordability; as the cost per vaccinated girl was increased from I$10 to I$25 (approximately $2 to $5 per dose), the financial costs for the 10-year scenario increased from >US$ 900 million to US$ 2.25 billion. Provided high coverage of young adolescent girls is feasible, and vaccine costs are lowered, HPV 16,18 vaccination could be very cost-effective even in the poorest countries, and provide comparable value for resources to other new vaccines such as rotavirus.