Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Cost-effectiveness analysis of PCV20 to prevent pneumococcal disease in the Canadian pediatric population.

This study assessed the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in Canadian infants aged <2 years versus the standard of care (SoC), a 13-valent pneumococcal conjugate vaccine (PCV13), or a potential 15-valent pneumococcal conjugate vaccine (PCV15). A decision-analytic Markov model was developed to compare PCV20 with PCV13 or PCV15 in a 2 + 1 schedule over 10 years. Vaccine effect estimates (direct and indirect) across all ages were informed by PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies. Epidemiologic, clinical, health state utilities, utility decrements, cost per event, and list price data were from Canadian sources where available. Clinical and economic outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and simple and complex otitis media (OM) were calculated for each strategy. Cost-effectiveness was evaluated from the publicly funded healthcare system perspective. Over 10 years, PCV20 versus PCV13 was estimated to avert over 11,000 IPD cases, 316,000 hospitalized and non-hospitalized pneumonia cases, 335,000 simple and complex OM cases, and 15,000 deaths, resulting in cost savings of over 3.2 billion Canadian dollars (CAD) and 47,000 more quality-adjusted life years (i.e. dominant strategy). Compared with PCV15, PCV20 was estimated to result in over 1.4 billion CAD in cost savings and 21,000 more QALYs (i.e. dominant strategy). PCV20 was dominant over both PCV13 and PCV15. Given broader serotype coverage, substantial incremental benefits and cost-savings, PCV20 should be considered as a replacement for the SoC in the publicly funded Canadian infant immunization program.

Public health impact of UK COVID-19 booster vaccination programs during Omicron predominance.

BACKGROUND: We aimed to estimate the public health impact of booster vaccination against COVID-19 in the UK during an Omicron-predominant period. RESEARCH DESIGN AND METHODS: A dynamic transmission model was developed to compare public health outcomes for actual and alternative UK booster vaccination programs. Input sources were publicly available data and targeted literature reviews. Base case analyses estimated outcomes from the UK's Autumn-Winter 2021-2022 booster program during January-March 2022, an Omicron-predominant period. Scenario analyses projected outcomes from Spring and in Autumn 2022 booster programs over an extended time horizon from April 2022-April 2023, assuming continued Omicron predominance, and explored hypothetical program alternatives with modified eligibility criteria and/or increased uptake. RESULTS: Estimates predicted that the Autumn-Winter 2021-2022 booster program averted approximately 12.8 million cases, 1.1 million hospitalizations, and 290,000 deaths. Scenario analyses suggested that Spring and Autumn 2022 programs would avert approximately 6.2 million cases, 716,000 hospitalizations, and 125,000 deaths; alternatives extending eligibility or targeting risk groups would improve these benefits, and increasing uptake would further strengthen impact. CONCLUSIONS: Boosters were estimated to provide substantial benefit to UK public health during Omicron predominance. Benefits of booster vaccination could be maximized by extending eligibility and increasing uptake.

Public health impact of booster vaccination against COVID-19 in the UK during Delta variant dominance in autumn 2021.

AIM: To evaluate the public health impact of the UK COVID-19 booster vaccination program in autumn 2021, during a period of SARS-CoV-2 Delta variant predominance. MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infectious-Recovered model was used to compare age-stratified health outcomes for adult booster vaccination versus no booster vaccination in the UK over a time horizon of September-December 2021, when boosters were introduced in the UK and the SARS-CoV-2 Delta variant was predominant. Model input data were sourced from targeted literature reviews and publicly available data. Outcomes were predicted COVID-19 cases, hospitalizations, post-acute sequelae of COVID-19 (PASC) cases, deaths, and productivity losses averted, and predicted healthcare resources saved. Scenario analyses varied booster coverage, virus infectivity and severity, and time horizon parameters. RESULTS: Booster vaccination was estimated to have averted approximately 547,000 COVID-19 cases, 36,000 hospitalizations, 147,000 PASC cases, and 4,200 deaths in the UK between September and December 2021. It saved over 316,000 hospital bed-days and prevented the loss of approximately 16.5 million paid and unpaid patient work days. In a scenario of accelerated uptake, the booster rollout would have averted approximately 3,400 additional deaths and 25,500 additional hospitalizations versus the base case. A scenario analysis assuming four-fold greater virus infectivity and lower severity estimated that booster vaccination would have averted over 105,000 deaths and over 41,000 hospitalizations versus the base case. A scenario analysis assuming pediatric primary series vaccination prior to adult booster vaccination estimated that expanding vaccination to children aged ≥5 years would have averted approximately 51,000 additional hospitalizations and 5,400 additional deaths relative to adult booster vaccination only. LIMITATIONS: The model did not include the wider economic burden of COVID-19, hospital capacity constraints, booster implementation costs, or non-pharmaceutical interventions. CONCLUSIONS: Booster vaccination during Delta variant predominance reduced the health burden of SARS-CoV-2 in the UK, releasing substantial NHS capacity.

Public health impact of pneumococcal conjugate vaccination: a review of measurement challenges.

INTRODUCTION: Modeling analyses have attempted to quantify the global impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease (PD), however these pediatric models face several challenges in obtaining comprehensive impact measurements. AREAS COVERED: We present several measurement challenges and discuss examples from recently published pediatric modeling evaluations. Challenges include estimating the number of infants fully or partially vaccinated with PCVs, inclusion of indirect effects of vaccination, accounting for various dosing schedules, capturing effect of PCVs on nonspecific, noninvasive PD, and inclusion of adult PCV use. EXPERT OPINION: The true impact of PCVs has been consistently underestimated in published analyses due to multiple measurement challenges. Nearly 100 million adults are estimated to have received PCV13 over the last decade globally, potentially preventing up to 662 thousand cases of PD. Approximately 4.1 million cases of invasive PD alone may have been averted through indirect protection. Estimates of PCV impact on noninvasive PD remain a challenge due to altered epidemiology. Program switches, incomplete vaccination, and private market uptake among children also confound PD impact estimates. Taken together, the number of averted PD cases from PCV use in the last ten years may be up to three times higher than estimated in previous studies.

Twenty-Year Public Health Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines in US Children.

Pneumococcal conjugate vaccines (PCVs) have been used in the United States since 2000. To assess the cumulative 20-year effect of PCVs on invasive pneumococcal disease (IPD) incidence among children <5 years of age, we analyzed Active Bacterial Core Surveillance data, conducted a literature review, and modeled expected and observed disease. We found that PCVs have averted >282,000 cases of IPD, including ≈16,000 meningitis, ≈172,000 bacteremia, and ≈55,000 bacteremic pneumonia cases. In addition, vaccination has prevented 97 million healthcare visits for otitis media, 438,914-706,345 hospitalizations for pneumonia, and 2,780 total deaths. IPD cases declined 91%, from 15,707 in 1997 to 1,382 in 2019. Average annual visits for otitis media declined 41%, from 78 visits/100 children before PCV introduction to 46 visits/100 children after PCV13 introduction. Annual pneumonia hospitalizations declined 66%-79%, from 110,000-175,000 in 1997 to 37,000 in 2019. These findings confirm the substantial benefits of PCVs for preventing IPD in children.

Ten year public health impact of 13-valent pneumococcal conjugate vaccination in infants: A modelling analysis.

Pneumococcal disease is a substantial contributor to illness and death in young children globally. The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 had a significant impact in preventing pneumococcal disease in both vaccinated children and unvaccinated individuals (through herd effect). A higher valent PCV13 replaced PCV7 in late 2009. This analysis was undertaken to assess how many cases and deaths have been averted over the last decade since PCV13 introduction. A model estimated the number of infants vaccinated annually with PCV13, as well as the number of cases and deaths of invasive pneumococcal disease, pneumococcal pneumonia, and acute otitis media cases averted. PCV13 vaccination was estimated to have prevented 175.2 million cases of all pneumococcal diseases and 624,904 deaths globally between 2010 and 2019. These results demonstrate the substantial public health impact of PCV13 and highlight the importance of increasing the global reach of PCV programs.

Comparative healthcare-associated costs of methicillin-resistant Staphylococcus aureus bacteraemia-infective endocarditis treated with either daptomycin or vancomycin.

Complex infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with high healthcare and societal costs; thus, evaluation of the costs and health benefits of interventions is an important consideration in a modern healthcare system. This study estimated the cost consequences of the use of daptomycin compared with vancomycin for the first-line treatment of patients with proven MRSA-induced bacteraemia-infective endocarditis (SAB-IE) with a vancomycin minimum inhibitory concentration (MIC) >1mg/L in the UK. A decision model was developed to assess total healthcare costs of treatment, including inpatient, outpatient and drug costs. Data were sourced from the literature (treatment efficacy and safety), a physician survey (resource use) and publicly available databases (unit costs). Assuming the same length of stay for daptomycin and vancomycin, the total healthcare costs per patient were £17917 for daptomycin and £17165 for vancomycin. However, extrapolating from published studies and supported by a physician survey, daptomycin was found to require fewer therapeutic switches and a shorter length of stay. When the length of stay was reduced from 42 days to 28 days, daptomycin saved £4037 per person compared with vancomycin. In conclusion, daptomycin is an effective and efficient alternative antibiotic for the treatment of SAB-IE. However, the level of cost saving depends on the extent to which local clinical practice allows early discharge of patients before the end of their antibiotic course when responding to treatment.

Decreasing immunity to hepatitis A virus infection among US adults: Findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012.

BACKGROUND: The clinical course of hepatitis A virus (HAV) infection is more severe with increased age. In the United States, surveillance data reported to CDC since 2011 indicate increases in both the absolute number of cases and the mean age of cases. Total antibody to HAV (anti-HAV) is a marker of immunity. METHODS: We analyzed National Health and Nutrition Examination Survey (NHANES) data for anti-HAV from respondents aged ≥ 2 years collected from 2007 to 2012 and compared with data collected 10 years earlier (1999-2006). For US-born adults aged ≥ 20 years, we estimated age-adjusted anti-HAV prevalence by demographic and other characteristics, evaluated factors associated with anti-HAV positivity and examined anti-HAV prevalence by decade of birth. RESULTS: The prevalence of anti-HAV among adults aged ≥ 20 years was 24.2% (95% CI 22.5-25.9) during 2007-2012, a significant decline from 29.5% (95% CI 28.0-31.1) during 1999-2006. Prevalence of anti-HAV was consistently lower in 2007-2012 compared to 1999-2006 by all characteristics examined. In 2007-2012, the lowest age-specific prevalence was among adults aged 30-49 years (16.1-17.6%). Factors significantly associated with anti-HAV positivity among adults were older age, Mexican American ethnicity, living below poverty, less education, and not having insurance. By decade of birth, the prevalence of anti-HAV was slightly lower in 2009-2012 than in 1999-2002, except among persons born from 1980 to 1989. CONCLUSIONS: NHANES data document very low prevalence of hepatitis A immunity among U.S. adults aged 30-49 years; waning of anti-HAV over time may be minimal. Improving vaccination coverage among susceptible adults should be considered.

Cost-effectiveness and public health benefit of secondary cardiovascular disease prevention from improved adherence using a polypill in the UK.

OBJECTIVE: To evaluate the public health and economic benefits of adherence to a fixed-dose combination polypill for the secondary prevention of cardiovascular (CV) events in adults with a history of myocardial infarction (MI) in the UK. DESIGN: Markov-model-based cost-effectiveness analysis, informed by systematic reviews, which identified efficacy, utilities and adherence data inputs. SETTING: General practice in the UK. PARTICIPANTS: Patients with a mean age of 64.7 years, most of whom are men with a recent or non-recent diagnosis of MI and for whom secondary preventive medication is indicated and well tolerated. INTERVENTION: Fixed-dose combination polypill (100 mg aspirin, 20 mg atorvastatin and 2.5, 5, or 10 mg ramipril) compared with multiple monotherapy. PRIMARY AND SECONDARY OUTCOME MEASURES: CV events prevented per 1000 patients; cost per life-year gained; and cost per quality-adjusted life-year (QALY) gained. RESULTS: The model estimates that for each 10% increase in adherence, an additional 6.7% fatal and non-fatal CV events can be prevented. In the base case, over 10 years, the polypill would improve adherence by ∼20% and thereby prevent 47 of 323 (15%) fatal and non-fatal CV events per 1000 patients compared with multiple monotherapy, with an incremental cost-effectiveness ratio (ICER) of £8200 per QALY gained. Probabilistic sensitivity analyses for the base-case assumptions showed an 81.5% chance of the polypill being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained compared with multiple monotherapy. In scenario analyses that varied structural assumptions, ICERs ranged between cost saving and £21,430 per QALY gained. CONCLUSIONS: Assuming that some 450,000 adults are at risk of MI, a 10 percentage point uptake of the polypill could prevent 3260 CV events and 590 CV deaths over a decade.The polypill appears to be a cost-effective strategy to prevent fatal and non-fatal CV events in the UK.

Quantifying Parameter and Structural Uncertainty of Dynamic Disease Transmission Models Using MCMC: An Application to Rotavirus Vaccination in England and Wales.

BACKGROUND: Two vaccines (Rotarix and RotaTeq) are highly effective at preventing severe rotavirus disease. Rotavirus vaccination has been introduced in the United Kingdom and other countries partly based on modeling and cost-effectiveness results. However, most of these models fail to account for the uncertainty about several vaccine characteristics and the mechanism of vaccine action. METHODS: A deterministic dynamic transmission model of rotavirus vaccination in the United Kingdom was developed. This improves on previous models by 1) allowing for 2 different mechanisms of action for Rotarix and RotaTeq, 2) using clinical trial data to understand these mechanisms, and 3) accounting for uncertainty by using Markov Chain Monte Carlo. RESULTS: In the long run, Rotarix and RotaTeq are predicted to reduce the overall rotavirus incidence by 50% (39%-63%) and 44% (30%-62%), respectively but with an increase in incidence in primary school children and adults up to 25 y of age. The vaccines are estimated to give more protection than 1 or 2 natural infections. The duration of protection is highly uncertain but has only impact on the predicted reduction in rotavirus burden for values lower than 10 y. The 2 vaccine mechanism structures fit equally well with the clinical trial data. Long-term postvaccination dynamics cannot be predicted reliably with the data available. CONCLUSION: Accounting for the joint uncertainty of several vaccine characteristics resulted in more insight into which of these are crucial for determining the impact of rotavirus vaccination. Data for up to at least 10 y postvaccination and covering older children and adults are crucial to address remaining questions on the impact of widespread rotavirus vaccination.

Increased uptake and new therapies are needed to avert rising hepatitis C-related end stage liver disease in England: modelling the predicted impact of treatment under different scenarios.

BACKGROUND & AIMS: Hepatitis C (HCV) related disease in England is predicted to rise, and it is unclear whether treatment at current levels will be able to avert this. The aim of this study was to estimate the number of people with chronic HCV infection in England that are treated and assess the impact and costs of increasing treatment uptake. METHODS: Numbers treated were estimated using national data sources for pegylated interferon supplied, dispensed, or purchased from 2006 to 2011. A back-calculation approach was used to project disease burden over the next 30 years and determine outcomes under various scenarios of treatment uptake. RESULTS: 5000 patients were estimated to have been treated in 2011 and 28,000 in total from 2006 to 2011; approximately 3.1% and 17% respectively of estimated chronic infections. Without treatment, incident cases of decompensated cirrhosis and hepatocellular carcinoma were predicted to increase until 2035 and reach 2290 cases per year. Treatment at current levels should reduce incidence by 600 cases per year, with a peak around 2030. Large increases in treatment are needed to halt the rise; and with more effective treatment the best case scenario predicts incidence of around 500 cases in 2030, although treatment uptake must still be increased considerably to achieve this. CONCLUSIONS: If the infected population is left untreated, the number of patients with severe HCV-related disease will continue to increase and represent a substantial future burden on healthcare resources. This can be mitigated by increasing treatment uptake, which will have the greatest impact if implemented quickly.

Mind the gaps: what's missing from current economic evaluations of universal HPV vaccination?

BACKGROUND: Since the original licensing of human papilloma virus (HPV) vaccination for women, evidence is accumulating of its effectiveness in preventing HPV-related conditions in men, and universal vaccination (vaccinating men and women) is now recommended in some countries. Several models of the cost-effectiveness of universal HPV vaccination have been published, but results have been mixed. This article assesses the extent to which economic studies have captured the range of values associated with universal HPV vaccination, and how this influences estimates of its cost-effectiveness. METHODS: Eight published economic evaluations of universal HPV vaccination were reviewed to identify which of the values associated with universal HPV vaccination were included in each analysis. RESULTS: Studies of the cost-effectiveness of universal HPV vaccination capture only a fraction of the values generated. Most studies focused on impacts on health and health system cost, and only captured these partially. A range of values is excluded from most studies, including impacts on productivity, patient time and costs, carers and family costs, and broader social values such as the right to access treatment. Further, those studies that attempted to capture these values only did so partially. DISCUSSION: Decisions to invest in universal HPV vaccination need to be based on a complete assessment of the value that it generates. This is not provided by existing economic evaluations. Further work is required to understand this value. First, research is required to understand how HPV-related health outcomes impact on society including, for instance, their impact on productivity. Second, consideration should be given to alternative approaches to capture this broader set of values in a manner useful to decisions-makers, such as multi-criteria decision analysis.

The dual impact of antiretroviral therapy and sexual behaviour changes on HIV epidemiologic trends in Uganda: a modelling study.

OBJECTIVES: Antiretroviral therapy (ART) availability in a population may influence risky sexual behaviour. We examine the potential impact of ART on the HIV epidemic, incorporating evidence for the impact that ART may have on risky sexual behaviour. METHODS: A mathematical model, parameterised using site-specific data from Uganda and worldwide literature review, was used to examine the likely impact of ART on HIV epidemiologic trends. We varied assumptions about rates of initiating ART, and changes in sexual partner turnover rates. RESULTS: Modelling suggests that ART will reduce HIV incidence over 20 years, and increase prevalence. Even in the optimistic scenario of ART enrollment beginning after just five months of infection (in HIV stage 2), prevalence is estimated to rise from a baseline of 10.5% and 8.3% among women and men, respectively, to at least 12.1% and 10.2%, respectively. It will rise further if sexual disinhibition occurs or infectiousness while on ART is slightly higher (2% female to male, rather than 0.5%). The conditions required for ART to reduce prevalence over this period are likely too extreme to be achievable. For example, if ART enrolment begins in HIV stage 1 (within the first 5 months of infection), and if risky sexual behaviour does not increase, then 3 of our 11 top fitting results estimate a potential drop in HIV prevalence by 2025. If sexual risk taking rises, it will have a large additional impact on expected HIV prevalence. Prevalence will rise despite incidence falling, because ART extends life expectancy. CONCLUSIONS: HIV prevalence will rise. Even small increases in partner turnover rates will lead to an additional substantial increase in HIV prevalence. Policy makers are urged to continue HIV prevention activities, including promoting sex education, and to be prepared for a higher than previously suggested number of HIV infected people in need of treatment.

Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus aureus has an impact on costs.

BACKGROUND: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. METHODS: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. RESULTS: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. CONCLUSIONS: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine types: quantification using a multi-type mathematical model.

INTRODUCTION: Estimates of human papillomavirus (HPV) vaccine impact in clinical trials and modelling studies rely on DNA tests of cytology or biopsy specimens to determine the HPV type responsible for a cervical lesion. DNA of several oncogenic HPV types may be detectable in a specimen. However, only one type may be responsible for a particular cervical lesion. Misattribution of the causal HPV type for a particular abnormality may give rise to an apparent increase in disease due to non-vaccine HPV types following vaccination ("unmasking"). METHODS: To investigate the existence and magnitude of unmasking, we analysed data from residual cytology and biopsy specimens in English women aged 20-64 years old using a stochastic type-specific individual-based model of HPV infection, progression and disease. The model parameters were calibrated to data on the prevalence of HPV DNA and cytological lesion of different grades, and used to assign causal HPV types to cervical lesions. The difference between the prevalence of all disease due to non-vaccine HPV types, and disease due to non-vaccine HPV types in the absence of vaccine HPV types, was then estimated. RESULTS: There could be an apparent maximum increase of 3-10% in long-term cervical cancer incidence due to non-vaccine HPV types following vaccination. CONCLUSION: Unmasking may be an important phenomenon in HPV post-vaccination epidemiology, in the same way that has been observed following pneumococcal conjugate vaccination.

Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model.

OBJECTIVES: To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity. DESIGN: A model of HPV transmission and disease previously used to inform UK vaccination policy, updated with recent evidence and expanded to include scenarios where the two vaccines differ in duration of protection, cross protection, and end points prevented. SETTING: United Kingdom. Population Males and females aged 12-75 years. MAIN OUTCOME MEASURE: Incremental cost effectiveness ratios for both vaccines and additional cost per dose for the quadrivalent vaccine to be equally cost effective as the bivalent vaccine. RESULTS: The bivalent vaccine needs to be cheaper than the quadrivalent vaccine to be equally cost effective, mainly because of its lack of protection against anogenital warts. The price difference per dose ranges from a median of £19 (interquartile range £12-£27) to £35 (£27-£44) across scenarios about vaccine duration, cross protection, and end points prevented (assuming one quality adjusted life year (QALY) is valued at £30,000 and both vaccines can prevent all types of HPV related cancers). CONCLUSIONS: The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost. The bivalent vaccine may have an advantage in preventing death due to cancer. However, considerable uncertainty remains about the differential benefit of the two vaccines.

Modelling borderline and mild dysplasia associated with HPV 6 and 11 infection.

INTRODUCTION: Low risk HPV types 6/11 are responsible for some low-grade cytological abnormalities. Most economic analyses of HPV vaccination have estimated the additional benefit of HPV 6/11 protection by the quadrivalent vaccine, over the bivalent, based on reduction of genital warts but have not included reduction in repeat smears and colposcopies due to low-grade abnormalities. We investigate the contribution of HPV types 6/11 to abnormal smears and associated costs in England. METHODS: The risk of borderline or mild dysplasia due to HPV 6/11 infection was estimated from a study of type-specific HPV DNA in cervical screening specimens collected throughout England. A Markov model representing 10 million women with HPV 6/11 or with no HPV infection from 24 to 64 years was developed to estimate the number of abnormal smears, subsequent repeat smears and colposcopies due to HPV 6/11 associated with borderline or mild dysplasia. Fitting was achieved by varying the force of infection, probability of borderline or mild dysplasia if HPV-uninfected or infected with HPV 6/11 and the duration of infection. RESULTS: The relative risks of borderline or mild dysplasia when infected with HPV 6/11 compared to not being HPV infected were 6.32 (95% credible interval 1.56-25.6) and 17.5 (1.02-300) respectively. Using best fitting parameters we find the costs incurred are between £170 and £195 per abnormal smear due to infection with HPV 6/11. CONCLUSIONS: In England, the impact of cytological abnormalities due to HPV 6/11 is relatively small, but not negligible. A vaccine that protects against HPV 6/11 infections could reduce costs associated with borderline and mild dysplasia, and associated colposcopies. These benefits should be considered when formulating immunisation policy, if possible. Smears and colposcopies in those uninfected with HPV far outnumber those in women infected with HPV 6/11.

Prevalence of human papillomavirus antibodies in males and females in England.

BACKGROUND: Most studies of human papillomavirus (HPV) epidemiology have employed DNA testing, which measures current infections. Serum antibodies offer a longer-term marker of infection in individuals who seroconvert and can therefore provide additional information about the exposure of populations to HPV. METHODS: Sera from a population-based sample of males and females aged 10 to 49 years, in England, were tested for type-specific HPV antibodies using a multiplexed competitive Luminex assay and previously defined cutoffs of 20, 16, 20, and 24 mMU mL for HPV 6, 11, 16, and 18, respectively. Seropositivity and geometric mean titers of seropositives were analyzed by HPV type, gender, and age. Catalytic models were developed to explore potential effects of antibody waning over time and changing risk of infection by age-cohort. RESULTS: Seroprevalence for HPV 6, 11, 16, and 18 was 16.4%, 5.7%, 14.7%, and 6.3%, respectively, among females and 7.6%, 2.2%, 5.0%, and 2.0%, respectively, among males. Seroprevalence in females was significantly higher than males (P < 0.001 for all types) and showed a decline in older ages that was not seen in males. There was no evidence of declining antibody titers with increasing age. Model results suggest that cohort effects mediated through changes in sexual behavior better explain the observed trend in seroprevalence than waning antibodies over time. CONCLUSIONS: Preimmunization HPV seroprevalence in England shows similar trends to reports from other developed countries. We find the lower seroprevalence in older females probably reflects changes in sexual behavior over the last few decades. This study provides baseline data to monitor the impact of the immunization programme.