Cost-effectiveness of nonavalent HPV vaccination in the Netherlands.

BACKGROUND: A bivalent human papillomavirus vaccine (2vHPV) is currently used in the Netherlands; a nonavalent vaccine (9vHPV) is also licensed. RESEARCH DESIGN AND METHODS: We compared the public health and economic benefits of 2vHPV- and 9vHPV-based vaccination strategies in the Netherlands over 100 years using a validated deterministic dynamic transmission metapopulation model. RESULTS: Compared to 2vHPV, the 9vHPV strategy averted an additional 3,245 cases of and 825 deaths from 9vHPV-strain-attributable cancers, 4,247 cases of and 190 deaths from recurrent respiratory papillomatosis (RRP), and 1,009,637 cases of anogenital warts (AGWs), with an incremental cost-effectiveness ratio (ICER) of €4,975 per quality-adjusted life year (QALY) gained. The ICER increased in a scenario with increased HPV vaccination coverage rates and was relatively robust to one-way deterministic sensitivity analyses, with variation in the disease utility parameter having the most impact. When catch-up vaccination for individuals ≤26 years of age was added to the model, vaccinating with 9vHPV averted additional cancers and AGWs compared to 2vHPV vaccination. CONCLUSION: Our analyses predict that transitioning from a 2vHPV- to a 9vHPV-based vaccination strategy would be cost-effective in the Netherlands.

Impact of the Corona Pandemic on Cervical Cancer Screening Assessment.

BACKGROUND/AIM: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. PATIENTS AND METHODS: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). RESULTS: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. CONCLUSION: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.

Costs of human papillomavirus vaccine delivery in low- and middle-income countries: A systematic review.

Vaccines to protect against human papillomavirus (HPV) infection are recommended for all adolescents by the World Health Organization (WHO) and are primarily delivered in school-based settings. This systematic review aims to summarize the available evidence on the cost of HPV vaccine delivery in low- and middle-income countries (LMICs). This updated evidence is eminent given recent global efforts to revitalize HPV vaccine delivery following the COVID-19 pandemic and can be used to inform planning for program sustainability. We carried out a systematic review of published literature reporting the costs of HPV vaccine delivery in LMICs published between 2005 and 2023. Eligibility criteria were developed using the Population, Intervention, Comparator, Outcome (PICO) framework, and studies that reported primary costing data and unit costs of HPV vaccine delivery were included. From the included studies, we extracted data such as phase of HPV vaccine implementation when costing was done, delivery strategy, and unit costs. Unit costs were converted into 2022 US$ for comparability. All included studies underwent critical appraisal using an adapted framework including Consolidated Health Economics Evaluation Reporting Standards criteria, the WHO-led consensus statement on vaccine delivery costing, and other frameworks. Our research identified 226 records, of which 15 met our inclusion criteria. Most studies (64 %) were carried out in African countries and during HPV vaccine pilots or demonstrations (60 %). Vaccine delivery cost ranged from $0.31 to $24.07 per dose for financial costs and $1.48 to $48.70 per dose for economic costs. The critical appraisal showed that most studies did not describe the uncertainty of reported delivery cost. Our systematic review evidence suggests that HPV vaccine delivery costs vary widely depending on country and stage of implementation when costing was done. Areas for further research include costing when programs are beyond the introduction phase and in LMICs outside of Africa.

Cost-effectiveness of primary human papillomavirus triage approaches among vaccinated women in Norway: A model-based analysis.

As Norway considers revising triage approaches following their first adolescent cohort with human papillomavirus (HPV) vaccination entering the cervical cancer screening program, we analyzed the health impact and cost-effectiveness of alternative primary HPV triage approaches for women initiating cervical cancer screening in 2023. We used a multimodeling approach that captured HPV transmission and cervical carcinogenesis to evaluate the health benefits, harms and cost-effectiveness of alternative extended genotyping and age-based triage strategies under five-yearly primary HPV testing (including the status-quo screening strategy in Norway) for women born in 1998 (ie, age 25 in 2023). We examined 35 strategies that varied alternative groupings of high-risk HPV genotypes ("high-risk" genotypes; "medium-risk" genotypes or "intermediate-risk" genotypes), number and types of HPV included in each group, management of HPV-positive women to direct colposcopy or active surveillance, wait time for re-testing and age at which the HPV triage algorithm switched from less to more intensive strategies. Given the range of benchmarks for severity-specific cost-effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved an age-based switch from a less to more intensive follow-up algorithm at age 30 or 35 years with HPV-16/18 genotypes in the "high-risk" group. The two potentially cost-effective strategies could reduce the number of colposcopies compared to current guidelines and simultaneously improve health benefits. Using age to guide primary HPV triage, paired with selective HPV genotype and follow-up time for re-testing, could improve both the cervical cancer program effectiveness and efficiency.

Human papillomavirus-associated anal squamous cell carcinoma: sociodemographic, geographic, and county-level economic trends in incidence rates-United States, 2001-2019.

BACKGROUND: Incidence of anal squamous cell carcinoma is increasing, but vaccination against human papillomavirus (HPV) and removal of precancerous anal lesions could prevent new cases. The overall HPV-associated cancer incidence is reported to be higher in rural populations and in counties with lower economic status. We assessed these differences specifically for HPV-associated anal squamous cell carcinoma and described the geographic, county-level economic, and sociodemographic variations in incidence rates and trends. METHODS: We analyzed data from the US Cancer Statistics to assess age-standardized incidence rates of HPV-associated squamous cell carcinomas among adults aged 18 years and older from 2001 to 2019. We calculated rate ratios and 95% confidence intervals to examine differences in incidence rates. We also quantified changes in incidence rates over time using joinpoint regression. RESULTS: From 2001 to 2019, 72 421 new cases of HPV-associated anal squamous cell carcinoma were diagnosed among women (2.8 per 100 000) and 37 147 among men (1.7 per 100 000). Age-standardized incidence rates were higher in the South compared with other census regions and in counties ranked in the bottom 25% and 25%-75% economically than in the top 25%. The overall incidence rate increased in women but remained stable in men during 2009-2019. Incidence rates increased in adults aged 50 years and older but decreased among those aged 40-44 years from 2001 to 2019 in women and from 2007 to 2019 in men. CONCLUSIONS: There were inequities in HPV-associated anal squamous cell carcinoma incidence by geographic and county-level economic characteristics. Failure to improve vaccine and treatment equity may widen existing disparities.

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.

Evaluating the cost-effectiveness of HPV vaccination for adolescent girls in Japan: A comparison of 2-valent, 4-valent, and 9-valent HPV vaccines with consideration of cross-protection.

OBJECTIVE: In April 2023, the Japanese Health Ministry panel approved the inclusion of the 9-valent human papillomavirus (9vHPV) vaccine in the National Immunization Program, alongside the 2-valent (2vHPV) and 4-valent HPV (4vHPV) vaccines. In response to this, we evaluated the cost-effectiveness of these three vaccines for routine immunization of girls aged 12-16 in Japan, considering the cross-protection of 2vHPV and 4vHPV vaccines. METHODS: We constructed an age-structured mathematical model for HPV transmission, aiming to quantify the economic and epidemiological effects of various HPV vaccination strategies over a 70-year period in Japan. We determined incremental costs and quality-adjusted life years (QALYs) for each strategy, applying a 3% annual discount. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of our model results, with all evaluations done in 2023. RESULTS: Our projections indicate that the HPV vaccination program in Japan will significantly reduce the incidence of HPV-related diseases. All HPV vaccination strategies, using the 2vHPV, 4vHPV, and 9vHPV vaccines, were found to be cost-effective compared to no vaccination, with incremental cost-effectiveness ratios of ¥971,447/QALY, ¥1,237,297/QALY, and ¥742,084/QALY, respectively. Direct comparisons between vaccines demonstrated that the 9vHPV vaccination was more cost-effective than the 2vHPV vaccination, whereas 4vHPV vaccination was dominated by 2vHPV vaccination. CONCLUSIONS: Our study validates the cost-effectiveness of implementing the 9vHPV vaccine as the primary option over the 2vHPV or 4vHPV vaccine for girls in Japan. These findings underscore the need to improve the acceptance rate and coverage of HPV vaccinations in the country.

Public health impact of 2-, 4-, and 9-valent HPV vaccination in females on cervical and noncervical diseases in men and women under different coverage scenarios in China: A simulation study.

The high prevalence of human papillomavirus (HPV) infection in China suggests there would be a substantial positive health impact of widespread vaccination against HPV. We adapted a previously described dynamic transmission model of the natural history of HPV infection and related diseases to the Chinese setting to estimate the public health impact in China of 2-valent (with and without cross-protection), 4-valent, and 9-valent HPV vaccination strategies. The model predicted the incidence and mortality associated with HPV-related diseases, including cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP), based on the various vaccination coverage rate (VCR) scenarios, over a 100-year time horizon. The public health impact of the 4 vaccination strategies was estimated in terms of cases and deaths averted compared to a scenario with no vaccination. Under the assumption of various primary and catch-up VCR scenarios, all 4 vaccination strategies reduced the incidence of cervical cancer in females and noncervical cancers in both sexes, and the 4-valent and 9-valent vaccines reduced the incidence of genital warts and RRP in both sexes. The 9-valent vaccination strategy was superior on all outcomes. The number of cervical cancer cases averted over 100 years ranged from ~ 1 million to ~ 5 million while the number of cervical cancer deaths averted was ~ 345,000 to ~ 1.9 million cases, depending on the VCR scenario. The VCR for primary vaccination was the major driver of cases averted.

A modelled analysis of the impact of COVID-19-related disruptions to HPV vaccination.

COVID-19 disrupted school attendance in many countries, delaying routine adolescent vaccination against human papillomavirus (HPV) in some settings. We used Policy1-Cervix, a dynamic model simulating HPV transmission, natural history, vaccination, cervical screening, and diagnosis of HPV-related cancers, to estimate the impact on HPV-related cancers from disruptions to HPV vaccination in a high-income setting. A baseline scenario of no disruption to HPV vaccination was modelled, which assumed uptake of the nonavalent vaccine at the age of 12 by 82.4% of females and 75.5% of males, as is the coverage in Australia. Additional lifetime HPV-related cancer cases were calculated for three disruption scenarios affecting one birth cohort (2008; aged 12 in 2020) compared to the baseline scenario: (1) 1-year delay (no doses missed); (2) 1- to 7-year delay (slow catch-up); (3) no catch-up (herd effects only). A fourth scenario assumed no catch-up HPV vaccination for two birth cohorts, that is all individuals born in 2008 and in 2009 missed vaccination (worst-case scenario). Compared to 1532 HPV-related cancer cases estimated for the baseline no disruption scenario, we found a 1-year delay could result in ≤0.3% more HPV-related cancers (n = 4) but the increase would be greater if catch-up was slower (5%; n = 70), and especially if there was no catch-up (49%; n = 750). Additional cancers for a single missed cohort were most commonly cervical (23% of the additional cases) and anal cancers (16%) in females and oropharyngeal cancers in males (20%). In the worst-case scenario of two birth cohorts missing vaccination, ≤62% more HPV-related cancers would be diagnosed (n = 1892). In conclusion, providing catch-up of missed HPV vaccines is conducted, short-term delays in vaccinating adolescents are unlikely to have substantial long-term effects on cancer.

MOnitoring human papillomavirus Vaccine effect on Infection and cErvical diseases (MOVIE): Protocol for a cohort study using electronic health records from Yinzhou, China.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

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.

EBCOG position statement on Inequalities in screening for cervical and breast cancer.

Gynaecological cancers, namely breast and cervical cancer represent a high burden in women's health. It is well established that cervical and breast cancer screening programmes are effective in reducing morbidity and mortality. It is of the most importance to define strategies to provide a universal access to screening. In European countries, significant progress has been made over the past years concerning screening strategies, namely the choice of screening test, its frequency as well as the age to start and stop the screening. Introduction of Human Papillomavirus vaccination programmes is also making a measurable impact to reduce cervical cancer prevalence and mortality. Our survey has shown a variation among European countries in delivery of cervical and breast cancer screening programmes. These variations can be due to organizational, economic or cultural reasons. The European Board and College of Obstetrics and Gynaecology calls for an implementation of a unified policy of prevention, screening and early detection of cervical and breast cancer across Europe to optimize clinical outcomes and reduce variations.

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.

The Relation Between Travel Distance and Overall Survival for HPV-Associated Cancers in a High-Burden State.

Purpose: To assess the association between travel distance to an academic health system and overall survival for patients with human papillomavirus (HPV)-associated cancers. Methods: Using hospital-based cancer registry data from 2005-2019, we calculated unidirectional travel distance from each patient's geocoded address to our academic health center through network analysis. We categorized distance as short (<25 miles), intermediate (25-74.9 miles), or long (≥75 miles). The primary outcome was time from the date of initial diagnosis to the date of death or last contact. We used multivariable Cox proportional hazards regression to evaluate the association between travel distance and overall survival. We also estimated the adjusted observed 5-year survival rate. Results: Patients with HPV-associated cancers traveling distances that were intermediate (hazard ratio [HR], 1.23; 95% CI, 1.06-1.43) and long (HR, 1.15; 95% CI, 1.01-1.32) had a higher hazard of death than the short-distance group. The adjusted 5-year observed survival rates for HPV-associated cancers were lowest in the intermediate-distance group (60.4%) compared with the long-(62.6%) and short-distance (66.2%) groups. Conclusions: Our findings indicate that travel distance to an academic health center was associated with overall survival for patients with HPV-associated cancers, reflecting the importance of considering travel burden in improving patient outcomes.

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.

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells.

OBJECTIVE: To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. METHODS: This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. RESULTS: Of 341 women, 134 (39.3%) had CIN 3-AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0-97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47-5.00 and HR 3.41, 95% CI 1.95-5.96, respectively). CONCLUSION: Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis.

BACKGROUND: To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. METHODS: Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme. RESULTS: Over the years 2021-2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1-130.4) and 146.8 million (114.1-161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6-169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14-3.82) USD in low-income countries to 44.83 (3.75-85.64) USD in high-income countries, assuming one dose confers 30-year protection. CONCLUSIONS: Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: a modeling study.

Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.

Impact, cost-effectiveness, and budget implications of HPV vaccination in Kenya: A modelling study.

BACKGROUND: Sub-Saharan Africa has the highest rate of cervical cancer cases and deaths worldwide. Kenya introduced a quadrivalent HPV vaccine (GARDASIL, hereafter referred to as GARDASIL-4) for ten-year-old girls in late 2019 with donor support from Gavi, the Vaccine Alliance. As Kenya may soon graduate from Gavi support, it is important to evaluate the potential cost-effectiveness and budget impact of the current HPV vaccine, and potential alternatives. METHODS: We used a proportionate outcomes static cohort model to evaluate the annual budget impact and lifetime cost-effectiveness of vaccinating ten-year-old girls over the period 2020-2029. We included a catch-up campaign for girls aged 11-14 years in 2020. We estimated cervical cancer cases, deaths, disability adjusted life years (DALYs), and healthcare costs (government and societal perspective) expected to occur with and without vaccination over the lifetimes of each cohort of vaccinated girls. For each of the four products available globally (CECOLIN©, CERVARIX©, GARDASIL-4©, and GARDASIL-9 ©), we estimated the cost (2021 US$) per DALY averted compared to no vaccine and to each other. Model inputs were obtained from published sources, as well as local stakeholders. RESULTS: We estimated 320,000 cases and 225,000 deaths attributed to cervical cancer over the lifetimes of the 14 evaluated birth cohorts. HPV vaccination could reduce this burden by 42-60 %. Without cross-protection, CECOLIN had the lowest net cost and most attractive cost-effectiveness. With cross-protection, CERVARIX was the most cost-effective. Under either scenario the most cost-effective vaccine had a 100 % probability of being cost-effective at a willingness-to-pay threshold of US$ 100 (5 % of Kenya's national gross domestic product per capita) compared to no vaccination. Should Kenya reach its target of 90 % coverage and graduate from Gavi support, the undiscounted annual vaccine program cost could exceed US$ 10 million per year. For all three vaccines currently supported by Gavi, a single-dose strategy would be cost-saving compared to no vaccination. CONCLUSION: HPV vaccination for girls is highly cost-effective in Kenya. Compared to GARDASIL-4, alternative products could provide similar or greater health benefits at lower net costs. Substantial government funding will be required to reach and sustain coverage targets as Kenya graduates from Gavi support. A single dose strategy is likely to have similar benefits for less cost.