Dataset Information

Projected impact of Cervarix™ vaccination on oncogenic human papillomavirus infection and cervical cancer in the United Kingdom.

ABSTRACT: We developed a dynamic compartmental model to assess the impact of HPV Universal Mass Vaccination (UMV) with Cervarix™, which offers protection against HPV16/18 and cross-protection against other cancer-causing types, using up-to-date efficacy data. Analyses were performed in the UK because of the large amount of high quality epidemiological data available. For each HPV type/group of types considered, the model was calibrated to 14 epidemiological datasets (prevalence of HPV infection, cervical intraepithelial neoplasia (CIN): CIN1, CIN2, CIN3 pre-screening and cervical cancer (CC) incidence over 10 y post-screening). Impacts of cross-protection, female catch-up vaccination, and additional male vaccination on oncogenic infections, high-grade CIN (CIN2+) and CC were evaluated. Our results show that female UMV with 80% coverage and cross-protection against high-risk types resulted in 81% CIN2+ and 88% CC reductions vs. 57% and 75%, respectively, without cross-protection. Vaccinating 40% of males and 80% of females was equivalent to 90% female-only coverage regarding CIN2+ (87% and 87%, respectively) and CC (93% and 94%, respectively) reductions. Female-only coverage of 80% substantially reduced male HPV16 and 18 infection due to herd protection (74% and 89%, respectively). Increasing female coverage to 90% reduced HPV16 and HPV18 infections in males relatively similarly to 80% female combined with 40% male coverage. Model outcomes strengthen previous conclusions about the significant added value of Cervarix™ cross-protection for CC prevention, the primary HPV vaccination public health priority. Regarding female CC prevention and male HPV16/18 infection, small increases in female coverage induce similar benefits to those achieved by additionally vaccinating men with 40% coverage.

SUBMITTER: Van Effelterre TP

PROVIDER: S-EPMC5155626 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Projected impact of Cervarix™ vaccination on oncogenic human papillomavirus infection and cervical cancer in the United Kingdom.

Van Effelterre Thierry P TP Hogea Cosmina C Taylor Sylvia M SM

Human vaccines & immunotherapeutics 20160101 1

We developed a dynamic compartmental model to assess the impact of HPV Universal Mass Vaccination (UMV) with Cervarix™, which offers protection against HPV16/18 and cross-protection against other cancer-causing types, using up-to-date efficacy data. Analyses were performed in the UK because of the large amount of high quality epidemiological data available. For each HPV type/group of types considered, the model was calibrated to 14 epidemiological datasets (prevalence of HPV infection, cervical ...[more]

PMID: 26090944

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Project description:BackgroundTo provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease.MethodsWe developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies.ResultsApproximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69-82%) and 69% (60-77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%.ConclusionWe demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S.

Project description:Dengue vaccines will soon provide a new tool for reducing dengue disease, but the effectiveness of widespread vaccination campaigns has not yet been determined. We developed an agent-based dengue model representing movement of and transmission dynamics among people and mosquitoes in Yucatán, Mexico, and simulated various vaccine scenarios to evaluate effectiveness under those conditions. This model includes detailed spatial representation of the Yucatán population, including the location and movement of 1.8 million people between 375,000 households and 100,000 workplaces and schools. Where possible, we designed the model to use data sources with international coverage, to simplify re-parameterization for other regions. The simulation and analysis integrate 35 years of mild and severe case data (including dengue serotype when available), results of a seroprevalence survey, satellite imagery, and climatological, census, and economic data. To fit model parameters that are not directly informed by available data, such as disease reporting rates and dengue transmission parameters, we developed a parameter estimation toolkit called AbcSmc, which we have made publicly available. After fitting the simulation model to dengue case data, we forecasted transmission and assessed the relative effectiveness of several vaccination strategies over a 20 year period. Vaccine efficacy is based on phase III trial results for the Sanofi-Pasteur vaccine, Dengvaxia. We consider routine vaccination of 2, 9, or 16 year-olds, with and without a one-time catch-up campaign to age 30. Because the durability of Dengvaxia is not yet established, we consider hypothetical vaccines that confer either durable or waning immunity, and we evaluate the use of booster doses to counter waning. We find that plausible vaccination scenarios with a durable vaccine reduce annual dengue incidence by as much as 80% within five years. However, if vaccine efficacy wanes after administration, we find that there can be years with larger epidemics than would occur without any vaccination, and that vaccine booster doses are necessary to prevent this outcome.

Project description:Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017.Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males).Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives.Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.

Project description:ImportanceOropharynx cancer (OPC) incidence has increased for several decades in the US. It is unclear when and how this trend will be affected by current HPV vaccination trends.ObjectiveTo assess the association of HPV vaccination with future OPC incidence in the US.Design, setting, and participantsThis population-based age-period-cohort analysis obtained OPC incidence data from the Surveillance, Epidemiology, and End Results program from 69 562 patients 34 to 83 years of age diagnosed with OPC. The HPV vaccination data were obtained from the National Immunization Survey-Teen (60 124 participants) and National Health Interview Survey (16 904 participants). Data were collected from January 1, 1992, to December 31, 2017. Age-period-cohort forecasting models projected expected 2018 to 2045 OPC incidence under a counterfactual scenario of no HPV vaccination and current levels of HPV vaccination, stratifying by sex. Data analyses were completed by December 2020.ExposuresAge- and sex-specific cumulative prevalence of HPV vaccination in 2016 to 2017 projected forward.Main outcomes and measuresProjected OPC incidence and number of OPC cases expected to be prevented by HPV vaccination.ResultsUnder current HPV vaccination rates, between 2018 and 2045, OPC incidence is projected to decrease in younger individuals (36-45 years of age: from 1.4 to 0.8 per 100 000 population; 46-55 years of age: from 8.7 to 7.2 per 100 000 population) but continue to increase among older individuals (70-83 years of age: from 16.8 to 29.0 per 100 000 population). The association of HPV vaccination with overall OPC incidence through 2045 will remain modest (no vaccination vs vaccination: 14.3 vs 13.8 per 100 000 population in 2045). By 2045 HPV vaccination is projected to reduce OPC incidence among individuals 36 to 45 years of age (men: 48.1%; women: 42.5%) and 46 to 55 years of age (men: 9.0%; women: 22.6%), but among those 56 years or older, rates are not meaningfully reduced. Between 2018 and 2045, a total of 6334 OPC cases will be prevented by HPV vaccination, of which 88.8% of such cases occur in younger age (≤55 years) groups.Conclusions and relevanceAccording to the projections of this population-based age-period-cohort study, current HPV vaccination rates will have a limited association with overall OPC incidence through 2045 because older individuals who have not yet been vaccinated remain at high risk for OPC. However, reductions in OPC incidence should occur among young and middle-aged adults, the group at lowest risk of diagnosis. These findings forecast a continued shift in the landscape of OPC to an older population.

Dataset Information

Projected impact of Cervarix™ vaccination on oncogenic human papillomavirus infection and cervical cancer in the United Kingdom.

Publications

Projected impact of Cervarix™ vaccination on oncogenic human papillomavirus infection and cervical cancer in the United Kingdom.

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