Sibling spillovers and the choice to get vaccinated: Evidence from a regression discontinuity design.

We investigate the effects of introducing population-wide free-of-charge Human Papillomavirus (HPV) vaccination programs on the targeted adolescent cohorts and their siblings. For identification, we rely on regression discontinuity designs and high-quality Danish administrative data to exploit that date of birth determines program eligibility. We find that the programs increased the HPV vaccine take-up of both the targeted children (53.2 percentage points for girls and 36.0 percentage points for boys) and their older same-sex siblings (4.5 percentage points for sisters and 3.5 percentage points for brothers). We show that while the direct effects of the programs reduced HPV vaccine take-up inequality, the spillover effects, in contrast, contributed to an increase in vaccine take-up inequality highlighting the potential importance of spillover effects in the determination of distributional consequences of public health programs. Finally, we find some evidence of cross-vaccine spillovers.

Cost-effectiveness analysis of human papillomavirus vaccines for the prevention of cervical cancer in India.

BACKGROUND: Human papillomavirus (HPV) vaccines represent an important strategic opportunity to prevent cervical cancer in low-middle income countries, such as India. The economic evaluation of HPV vaccines is crucial to inform public-health decisions; however, the scarce economic evaluations from India have focused on the value for money of bivalent vaccines and took a healthcare perspective. The aim of this study is to conduct a cost-effectiveness analysis of all available HPV vaccines in India. MATERIAL AND METHODS: The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to evaluate the cost-effectiveness of HPV vaccination of 12-year-old girls in India, from both healthcare and societal perspectives. Cervical cancer cases, deaths averted and the incremental cost per Disability Adjusted Life Years (DALY) averted were reported as primary outcomes. Sensitivity analysis was undertaken to handle any uncertainty or variability in the results. RESULTS: Compared with no vaccination, the incremental cost per DALY averted was USD 362.78 for nonavalent vaccine, USD 393.16 for quadrivalent vaccine and USD 432.24 for bivalent vaccine from a healthcare perspective. From a societal perspective, the incremental cost per DALY averted was USD 334.28 for nonavalent vaccine, USD 364.67 for quadrivalent vaccine and USD 403.75 for bivalent vaccine. Assuming constant prices per dose for all vaccines, the nonavalent vaccine dominated both quadrivalent and bivalent vaccines, indicating that it is the more cost-effective strategy. CONCLUSION: Vaccinating girls against HPV is a cost-effective strategy to reduce the incidence of cervical cancer and mortality due to cervical cancer in India.

Health impact and cost effectiveness of implementing gender-neutral HPV vaccination in Japan.

OBJECTIVE: To assess the public health impact and cost effectiveness of gender-neutral vaccination (GNV) versus female-only vaccination (FOV) with human papillomavirus (HPV) vaccination in Japan. METHODS: We modeled the public health impact and cost effectiveness of GNV versus FOV to prevent HPV-associated diseases in Japan over the next 100 years. We used one-way sensitivity analyses to examine the impact of varying key model input parameters and conducted scenario analyses to explore the effects of varying the vaccination coverage rate (VCR) of each cohort. RESULTS: In the base-case analysis, GNV averted additional cancer cases (17,228 female/6,033 male) and deaths (1,892 female/1,849 male) compared to FOV. When all HPV-associated diseases were considered, GNV had an incremental cost-effectiveness ratio of ¥4,732,320 (US$35,987)/quality-adjusted life year gained compared to FOV. The model was most sensitive to the discount rate and the disutility associated with HPV-related diseases. GNV had greater relative public health benefits when the female VCR was lower and was cost effective at a female VCR of 30%. CONCLUSIONS: Immediate implementation of GNV would reduce the disease burden and mortality associated with HPV in Japan, and would be cost effective compared to FOV if the female VCR remains low (30%).

Human papillomavirus (HPV) is a common sexually transmitted infection and, in Japan, the prevalence of HPV infection and the incidence of its associated diseases are high among both men and women. In the present manuscript we modeled the public health impact and cost effectiveness of gender-neutral vaccination versus female-only vaccination to prevent HPV-associated diseases in Japan over the next 100 years and found that immediate implementation of a gender-neutral vaccination strategy would reduce the burden and mortality associated with HPV in Japan.

Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India.

BACKGROUND: Cervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus (HPV) vaccination to include a single-dose option in addition to the two-dose option, which could make HPV vaccination programmes easier to implement and more affordable. METHODS: We combined projections from a type-specific HPV transmission model and a cancer progression model to assess the health and economic effects of HPV vaccination at national and state level in India. The models used national and state-specific Indian demographic, epidemiological and cost data, and single-dose vaccine efficacy and immunogenicity data from the International Agency for Research on Cancer India vaccine trial with 10-year follow-up. We compared single-dose and two-dose HPV vaccination for a range of plausible scenarios regarding single-dose vaccine protection, coverage and catch-up. We used a healthcare sector payer perspective with a time horizon of 100 years. RESULTS: Under the base-case scenario of lifelong protection of single-dose vaccination in 10-year-old girls with 90% coverage, the discounted incremental cost-effectiveness ratio (ICER) of nationwide vaccination relative to no vaccination was US$406 (₹INR30 000) per DALY (disability-adjusted life-years) averted. This lay below an opportunity-cost-based threshold of 30% Indian gross domestic product per capita in each Indian state (state-specific ICER range: US$67-US$593 per DALY averted). The ICER of two-dose vaccination versus no vaccination vaccination was US$1404 (₹INR104 000). The ICER of two-dose vaccination versus single-dose vaccination, assuming lower initial efficacy and waning of single-dose vaccination, was at least US$2282 (₹INR169 000) per DALY averted. CONCLUSIONS: Nationwide introduction of single-dose HPV vaccination at age 10 in India is highly likely to be cost-effective whereas extending the number of doses from one to two would have a less favourable profile.

Barriers to human papillomavirus vaccine uptake: role of state religiosity and healthcare professionals' participation in a state vaccine program.

BACKGROUND: Despite the known benefits of preventing human papillomavirus (HPV)-related cancers, HPV vaccine coverage is low in the United States. Grounded in Social Ecological theory, we assessed the macro-level (state) and meso-level (organization) factors associated with HPV vaccine initiation and up-to-date. METHODS: Data from 2020 National Immunization Survey-Teen were used to study a sample of 20 163 US adolescents (aged 13-17 years). The data were collected from each teen's parents or guardians and health-care professionals. Weighted prevalence estimates were calculated, and multivariable regression analyses were conducted. RESULTS: The prevalence of HPV vaccine initiation was 75.1% and of remaining up-to-date was 58.6%. At the macro level, teens living in states with high and moderate religiosity had lower odds of HPV vaccine initiation (high religiosity adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.50 to 0.78; moderate religiosity AOR = 0.68, 95% CI = 0.55 to 0.85) and up-to-date (high religiosity AOR = 0.69, 95% CI = 0.56 to 0.85; moderate religiosity AOR = 0.74, 95% CI = 0.61 to 0.91) than states with low religiosity. At the meso level, when none of their healthcare professionals ordered vaccine from the state, teens had lower odds of initiation (AOR = 0.68, 95% CI = 0.53 to 0.87) and up-to-date (AOR = 0.76, 95% CI = 0.60 to 0.95) than teens whose healthcare professionals ordered vaccine from the state. In addition, race and ethnicity, age, mother's education level, household income, well-child examination status, and doctor's recommendation were significantly associated with HPV vaccine uptake. CONCLUSION: A multiprong approach is needed to address religious and systemic barriers to HPV vaccination and expand healthcare professionals' access and enrollment in state vaccine initiatives, such as the Vaccine for Children program.

Public health impact and cost-effectiveness of switching from bivalent to nonavalent vaccine for human papillomavirus in Norway: incorporating the full health impact of all HPV-related diseases.

AIM: The objective of this study was to estimate and compare the cost-effectiveness of switching from a bivalent to a nonavalent human papillomavirus (HPV) vaccination program in Norway, incorporating all nonavalent vaccine-preventable HPV-related diseases and in the context of the latest cervical cancer screening program. METHODS: A well-established dynamic transmission model of the natural history of HPV infection and disease was adapted to the Norwegian population. We determined the number of cases of HPV-related diseases and subsequent number of deaths, and the economic burden of HPV-related disease under the current standard of care conditions of bivalent and nonavalent vaccinations of girls and boys aged 12 years. RESULTS: Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of recurrent respiratory papillomatosis (RRP) over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. Total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3-9.4 billion NOK [€915-925 million] for bivalent vaccination). A switch to nonavalent vaccination had a higher vaccination cost (4.4 billion NOK [€433 million] vs. 2.7 billion NOK [€266 million] for bivalent vaccination) but resulted in a savings of 627-694 million NOK [€62-68 million] in treatment costs. A switch to nonavalent vaccination demonstrated an incremental cost-effectiveness ratio of 102,500 NOK (€10,086) per QALY versus bivalent vaccination. CONCLUSIONS: Using a model that incorporated the full range of HPV-related diseases, and the latest cervical cancer screening practices, we found that switching from bivalent to nonavalent vaccination would be considered cost-effective in Norway.

Human papillomavirus (HPV) is a sexually transmitted infection that is common in Norway. Vaccination against HPV has substantially reduced the burden of HPV-related diseases globally. The HPV vaccine is available in bivalent, quadrivalent, and nonavalent forms. The bivalent vaccine is currently used in the Norwegian national immunization program, but the nonavalent vaccine is also licensed in Norway. In order to gain a more complete understanding of the benefits of nonavalent vaccination, it is necessary to evaluate the cost-effectiveness of switching from the bivalent vaccine to the nonavalent vaccine in light of the full array of vaccine-preventable diseases, including both cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP). Our results show that, when the full range of HPV-related diseases is considered, nonavalent vaccination would be cost-effective relative to bivalent vaccination in Norway. Compared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of RRP over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. While total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3-9.4 billion NOK [€915­925 million] for bivalent vaccination), switching to the nonavalent strategy resulted in a savings of 627­694 million NOK [€62­68 million] in treatment costs compared to the bivalent strategy.

Fine-grained mathematical modeling for cost-effectiveness evaluation of public health policies for cervical cancer, with application to a Colombian case study.

BACKGROUND: Cervical cancer (CC) is globally ranked fourth in terms of incidence and mortality among women. Vaccination against Human Papillomavirus (HPV) and screening programs can significantly reduce CC mortality rates. Hence, executing cost-effective public health policies for prevention and surveillance is crucial. However, defining policies that make the best use of the available resources is not easy, as it requires predicting the long-term costs and results of interventions on a changing population. Since the simpler task of predicting the results of public health policies is difficult, devising those that make the best usage of available resources is an arduous challenge for decision-makers. METHODS: This paper proposes a fine-grained epidemiological simulation model based on differential equations, to effectively predict the costs and effectiveness of CC public health policies that include vaccination and screening. The model represents population dynamics, HPV transmission within the population, likelihood of infection clearance, virus-induced appearance of precancerous lesions and eventually CC, as well as immunity gained with vaccination and early detection with screening. RESULTS: We offer a compartmentalized modeling approach that separates population, epidemics, and intervention concerns. We instantiate models with actual data from a Colombian case study and analyze their results to show how our modeling approach can support CEA studies. Moreover, we implement models in an open-source software tool to simultaneously define and evaluate multiple policies. With the support of the tool, we analyze 54 policies within a 30-year time horizon and use as a comparator the CC policy that has been used until recently. We identify 8 dominant policies, the best one with an ICER of 6.3 million COP (Colombian Pesos) per averted DALY. We also validate the modeling approach against the available population and HPV epidemic data. The effects of uncertainty in the values of key parameters (discount rate, sensitivity of screening tests) is evaluated through one-way sensitivity analysis. CONCLUSIONS: Our modeling approach can provide valuable support for healthcare decision-makers. The implementation into an automated tool allows customizing the analysis with country-specific data, flexibly defining public health policies to be evaluated, and conducting disaggregate analyses of their cost and effectiveness.

A semi-Markov multistate cure model for estimating intervention effects in stepped wedge design trials.

Multistate models are useful for studying exposures that affect transitions among a set of health states. However, they can be challenging to apply when exposures are time-varying. We develop a multistate model and a method of likelihood construction that allows application of the model to data in which interventions or other exposures can be time-varying and an individual may to be exposed to multiple intervention conditions while progressing through states. The model includes cure proportions, reflecting the possibility that some individuals will never leave certain states. We apply the approach to analyze patient vaccination data from a stepped wedge design trial evaluating two interventions to increase uptake of human papillomavirus vaccination. The states are defined as the number of vaccine doses the patient has received. We model state transitions as a semi-Markov process and include cure proportions to account for individuals who will never leave a given state (e.g. never receive their next dose). Multistate models typically quantify intervention effects as hazard ratios contrasting the intensities of transitions between states in intervention versus control conditions. For multistate processes, another clinically meaningful outcome is the change in the percentage of the study population that has achieved a specific state (e.g. completion of all required doses) by a specific point in time due to an intervention. We present a method for quantifying intervention effects in this manner. We apply the model to both simulated and real-world data and also explore some conditions under which such models may give biased results.

Exploring HPV vaccination policy and payer strategies for opportunities to improve uptake in safety-net settings.

Introduction: We explored priorities and perspectives on health policy and payer strategies for improving HPV vaccination rates in safety-net settings in the United States. Methods: We conducted qualitative interviews with policy and payer representatives in the greater Los Angeles region and state of New Jersey between December 2020 and January 2022. Practice Change Model domains guided data collection, thematic analysis, and interpretation. Results: Five themes emerged from interviews with 11 policy and 8 payer participants, including: (1) payer representatives not prioritizing HPV vaccination specifically in incentive-driven clinic metrics; (2) policy representatives noting region-specific HPV vaccine policy options; (3) inconsistent motivation across policy/payer groups to improve HPV vaccination; (4) targeting of HPV vaccination in quality improvement initiatives suggested across policy/payer groups; and (5) COVID-19 pandemic viewed as both barrier and opportunity for HPV vaccination improvement across policy/payer groups. Discussion: Our findings indicate opportunities for incorporating policy and payer perspectives into HPV vaccine improvement processes. We identified a need to translate effective policy and payer strategies, such as pay-for-performance programs, to improve HPV vaccination within safety-net settings. COVID-19 vaccination strategies and community efforts create potential policy windows for expanding HPV vaccine awareness and access.

Updated estimate of the annual direct medical cost of screening and treatment for human papillomavirus associated disease in the United States.

The annual direct medical cost attributable to human papillomavirus (HPV) in the United States over the period 2004-2007 was estimated at $9.36 billion in 2012 (updated to 2020 dollars). The purpose of this report was to update that estimate to account for the impact of HPV vaccination on HPV-attributable disease, reductions in the frequency of cervical cancer screening, and new data on the cost per case of treating HPV-attributable cancers. Based primarily on data from the literature, we estimated the annual direct medical cost burden as the sum of the costs of cervical cancer screening and follow-up and the cost of treating HPV-attributable cancers, anogenital warts, and recurrent respiratory papillomatosis (RRP). We estimated the total direct medical cost of HPV to be $9.01 billion annually over the period 2014-2018 (2020 U.S. dollars). Of this total cost, 55.0% was for routine cervical cancer screening and follow-up, 43.8% was for treatment of HPV-attributable cancer, and less than 2% was for treating anogenital warts and RRP. Although our updated estimate of the direct medical cost of HPV is slightly lower than the previous estimate, it would have been substantially lower had we not incorporated more recent, higher cancer treatment costs.

The Cost Analysis of Human Papillomavirus Vaccination Program in Indonesia.

OBJECTIVES: This study aimed to analyze and describe the cost of HPV vaccination program in Indonesia. METHODS: This study identified the cost-related HPV vaccination program implemented in Makassar, Manado, and Surabaya cities, Indonesia, according to the previous activities performed. Cost information was collected and analyzed in each specific activity for each cost components, using the HPV vaccination module of the World Health Organization Cervical Cancer Prevention and Control Costing tool. RESULTS: According to the Cervical Cancer Prevention and Control Costing tool, the recurrent costs, both financial and economic costs, dominated the HPV vaccination program costs in Surabaya (US dollars [USD] 264 618; USD 268 724), Makassar (USD 166 852; USD 293 300), and Manado (USD 270 815; USD 270 946), with a total cost of USD 702 285 for financial cost and USD 832 970 for economic cost. Vaccine procurement drives the recurrent cost. CONCLUSIONS: The implementation of demonstration program in Surabaya, Makassar, and Manado cities was considerably succeed. Any prediction related to the cost of implementation of HPV vaccination in Indonesia can be calculated and used to advocate regional or national government.

Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018-2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria.

Impact of HPV vaccination on HPV infection and cervical related disease burden in real-world settings (HPV-RWS): protocol of a prospective cohort.

BACKGROUND: Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. METHODS: This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. DISCUSSION: This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9-45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. TRIAL REGISTRATION: This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.

Comprehensive approach to costing cervical cancer prevention and control: a case study in the United Republic of Tanzania using the Cervical Cancer Prevention and Control Costing (C4P) tool.

BACKGROUND: The World Health Organization (WHO) has developed a costing tool, the Cervical Cancer Prevention and Control Costing (C4P) tool, to estimate the comprehensive cost of cervical cancer primary, secondary and tertiary prevention in low- and middle-income countries. The tool was piloted in the United Republic of Tanzania, a country with a high incidence of cervical cancer with 62.5 cases per 100,000 women in 2020. This paper presents the costing tool methods as well as the results from the pilot in Tanzania. METHODS: The C4P tool estimates the incremental costs of cervical cancer prevention and control programmes. It estimates the financial (monetary costs to the government) and economic costs (opportunity costs). For the pilot, the study team collected data on costs and programme assumptions for human papillomavirus (HPV) vaccination of 14-year-old girls and scaling up of cervical cancer screening (visual inspection with acetic acid and HPV-DNA testing) and treatment for women for 2020-2024. Assumptions were made on how vaccination coverage would increase over the 5 years as well as developing additional screening and treatment capacity through health personnel training and infrastructure strengthening. RESULTS: The total financial and economic costs of the comprehensive programme during 2020-2024 are projected to be US$68 million and US$124 million, respectively. The financial and economic costs of a fully immunized girl with HPV vaccine are estimated to be US$6.68 and US$17.31, respectively, while the costs per woman screened for cervical cancer are, on average, US$4.02 and US$5.83, respectively; US$6.44 and US$9.37 for pre-cancer treatment, respectively; and US$101 and US$107 for diagnosis of invasive cancer, respectively. The cost of treating and managing invasive cancer range from US$7.05 and US$7.83 for outpatient palliative care to US$800.21 and US$893.80 for radiotherapy, respectively. CONCLUSIONS: The C4P costing tool can assist national cervical cancer programmes to estimate monetary resources needed as well as opportunity costs of reducing national cervical cancer incidence through primary, secondary and tertiary prevention.

Mathematical Models for Evaluating Effectiveness and Cost-Effectiveness of Cervical Cancer Control Policies in Populations Including Women Living With Human Immunodeficiency Virus: A Scoping Review.

OBJECTIVES: Mathematical modeling is increasingly used to inform cervical cancer control policies, and model-based evaluations of such policies in women living with human immunodeficiency virus (HIV) are an emerging research area. We did a scoping review of published literature to identify research gaps and inform future work in this field. METHODS: We systematically searched literature up to April 2022 and included mathematical modeling studies evaluating the effectiveness or cost-effectiveness of cervical cancer prevention strategies in populations including women living with HIV. We extracted information on prevention strategies and modeling approaches. RESULTS: We screened 1504 records and included 22 studies, almost half of which focused on South Africa. We found substantial between-study heterogeneity in terms of strategies assessed and modeling approaches used. Fourteen studies evaluated cervical cancer screening strategies, 7 studies assessed human papillomavirus vaccination (with or without screening), and 1 study evaluated the impact of HIV control measures on cervical cancer incidence and mortality. Thirteen conducted cost-effectiveness analyses. Markov cohort state-transition models were used most commonly (n = 12). Most studies (n = 17) modeled the effect of HIV by creating HIV-related health states. Thirteen studies performed model calibration, but 11 did not report the calibration methods used. Only 1 study stated that model code was available upon request. CONCLUSIONS: Few model-based evaluations of cervical cancer control strategies have specifically considered women living with HIV. Improvements in model transparency, by sharing information and making model code publicly available, could facilitate the utility of these evaluations for other high disease-burden countries, where they are needed for assisting policy makers.

The Clinical and Economic Impact of a Nonavalent Versus Bivalent Human Papillomavirus National Vaccination Program in Taiwan.

OBJECTIVES: This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan. METHODS: A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types. RESULTS: The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year. CONCLUSIONS: A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Cost-Benefit Analysis of Human Papillomavirus Vaccine in Iran.

Despite increasing global attention to the national human papillomavirus (HPV) immunization program, this program is controversial in Iran. Evidence indicates that HPV vaccination is not cost-effective in Iran. Using cost-effectiveness analysis for decision-making about public health interventions such as vaccination is controversial because its potential benefits may not fit this framework. This study aimed to evaluate the economic effects of the HPV vaccination by cost-benefit analysis (CBA) using bivalent and quadrivalent in Iran in 2020. We performed a CBA from a societal perspective. We used two approaches of the vaccine's economic benefits: willingness to pay by discrete choice experiment and cost of illness. Costs only included the vaccine cost. The cost of two doses of bivalent and quadrivalent vaccines were US $29 and the US $151, respectively (US $1 = IRR 42,000). The benefits of bivalent and quadrivalent vaccines were US $ - 432, US $380 per person using the willingness to pay approach, and they were US $7375 and US $6590 thorough cost-of-illness approach. The cost-benefit ratio (CBR) of bivalent and quadrivalent vaccines was - 15.11 and 2.51 by the willingness to pay approach, and 258.12 and 43.51 by the cost of illness approach. This study confirms the benefits of the national bivalent and quadrivalent vaccination programs and provides reliable evidence for policy-makers programming HPV vaccination.

The Use of Medical Claims Data for Identifying Missed Opportunities for HPV Immunization Among Privately Insured Adolescents in the State of Iowa.

BACKGROUND: Rates of adolescent human papillomavirus (HPV) vaccination remain low, despite decades of safety and effectiveness data. We sought to quantify the extent of missed opportunities (MOs) for HPV vaccination among adolescents ages 11 to 13 in Iowa and compare the number of these MOs by gender and rurality. METHODS: Medical claims data from a midwestern insurance provider were used to calculate total numbers of MOs for HPV vaccination for adolescents with continuous health insurance enrollment between ages 11 and 13 (n = 14,505). We divided MOs into several categories: total, among non-initiators, occurring before initiation, occurring after the first dose, and occurring between first and last dose. Finally, we used t-tests to perform subgroup comparisons (urban vs. rural; male vs. female). RESULTS: Over half of adolescents failed to initiate vaccination by age 13. The majority of MOs occurred prior to initiation. Urban adolescents had more MOs than rural counterparts and males tended to have more MOs than females. Females experienced significantly fewer overall MOs than males 5.98 (SD = 5.49) compared to 6.18 (SD = 6.04) for males. Additionally, among non-initiators, urban females had significantly more MOs overall (M = 7.13; SD = 6.41) compared to rural females (M = 6.58; SD = 5.51). CONCLUSIONS: Results highlight the extent of MOs that occur at the critical time period between ages 11 and 13. A lack of opportunity was not the barrier to HPV vaccination, particularly among both males and urban adolescents. It will be critical for providers to use known strategies to reduce MOs and utilize all adolescent visits to ensure vaccination is completed by age 13.

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region. METHODS: We systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country. RESULTS: We found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years). CONCLUSIONS: Most studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.