Development of a quality framework for models of cervical screening and its application to evaluations of the cost-effectiveness of HPV vaccination in developed countries

BackgroundHPV vaccination has now been introduced in most developed countries, but this has occurred in the context of established cervical cancer screening mechanisms which provide population-level protection against the most common HPV-related cancer. Therefore, estimating the cost-effectiveness of HPV vaccination to further reduce HPV-related disease depends in large part on the estimation of the effectiveness of the cervical screening ‘background’. The aim of this study was to systematically review and assess methods for simulating cervical screening in decision analytic models used for evaluation of HPV vaccination.MethodsExisting quality frameworks for economic models were extended to develop a specific quality framework for models of cervical screening. This involved domains for model structure, parameterisation (data sources) and validation (consistency). A systematic review of economic evaluations of HPV vaccination was then conducted, and assessment of cervical screening model components was then performed via application of the new quality framework.ResultsGenerally, models took into account population-level cervical screening participation, but were inconsistent in their approach to modelling abnormal smear management, diagnostic evaluation and treatment of precancerous disease. There was also considerable variability in the accuracy of modelling clinical pathways and the scope of validation performed for screening-related outcomes, with focus directed towards cervical cancer targets. Only a few models comprehensively validated against observed pre-cancerous abnormalities.ConclusionModels of HPV vaccination in developed countries can be improved by further attention to the ‘background’ modelling of secondary protection via cervical screening. The quality framework developed for this review can be used to inform future HPV vaccination evaluations, including evaluations of the cost-effectiveness of male vaccination and next generation HPV vaccines, and to assess models used to evaluate new cervical screening technologies and recommendations.     

Cost-effectiveness and equity impacts of three HPV vaccination programmes for school-aged girls in New Zealand

Background

As with many high-income countries, vaccination coverage against human papilloma virus (HPV) infection is not high in New Zealand (NZ) at 47% in school-aged girls for three doses. We estimate the health gains, net-cost and cost-effectiveness of the currently implemented HPV national vaccination programme of vaccination dispersed across schools and primary care, and two alternatives: school-based only (assumed coverage as per Australia: 73%), and mandatory school-based vaccination but with opt-out permitted (coverage 93%). We also generate estimates by social group (sex, ethnic and deprivation group).

Methods

A Markov macro-simulation model was developed for 12-year-old girls and boys in 2011, with future health states of: cervical cancer, pre-cancer (CIN I–III), genital warts, and three other HPV-related cancers (oropharyngeal, anal, vulvar cancer). In each state health sector costs, including additional health sector costs from extra life, and quality-adjusted life years (QALYs) were accumulated.

Results

The current HPV vaccination programme has an estimated cost-effectiveness of NZ$18,800/QALY gained (about US$9700/QALY gained using the OECD's purchasing power parities; 95% UI: US$6900 to $33,700) compared to the status quo in NZ prior to 2008 (no vaccination, screening alone). The incremental cost-effectiveness ratio (ICER) of an intensive school-based only programme of girls, compared to the current situation, was US$33,000/QALY gained. Mandatory vaccination appeared least cost-effective (ICER compared to school-based of US$117,000/QALY gained, but with wide 95% uncertainty limits from $56,000 to $220,000). All interventions generated more QALYs per 12-year-old for Māori (indigenous population) and people living in deprived areas (range 5–25% greater QALYs gained).

Interpretation

A more intensive school-only vaccination programme seems warranted. Reductions in vaccine price will greatly improve cost-effectiveness of all options, possibly making a law for mandatory vaccination optimal from a health sector perspective. All interventions could reduce ethnic and socioeconomic disparities in HPV-related disease.     

Regional variations in human papillomavirus prevalence across time in NHANES (2003–2014)

IntroductionThe consequences of low human papillomavirus (HPV) vaccination in Census regions with higher incidence of cervical cancer may contribute to continued disparities. Our purpose was to evaluate regional variations in HPV prevalence across time.MethodsRepeated cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2003–2014 were examined. Participants included females 14 to 34 years old who provided adequate vaginal samples for HPV DNA typing (N = 6387). Region of residence and HPV vaccination status associations with HPV prevalence were examined using chi-square and multivariable logistic regression. HPV types were grouped according to vaccine-type HPV (types 6, 11, 16, 18) and risk (high or low-risk). Time and vaccination status were included in subsequent models for post-licensure survey cycles (2007–2014) to assess their effects on observed associations.ResultsNo decreases in vaccine-type HPV prevalence were found between the prevaccine cycles (2003–2006) and early post-licensure cycles (2007–2010, p > 0.05). Vaccine-type HPV prevalence decreased in late post-licensure years (2011–2014) compared to prevaccine years (2003–2006, p = 0.001). The highest prevalence of vaccine-type HPV occurred in the South (8.6%) and Midwest (8.6%), followed by the West (4.8%), and the Northeast (3.5%) in late post-licensure years. Lower odds of vaccine-type HPV across time in post-licensure survey cycles were found to be attributable to time, and more strongly to HPV vaccination.ConclusionsThere were regional variations in vaccine-type HPV prevalence between prevaccine and post-licensure years. These decreases appeared to be at least partially attributable to HPV vaccination. Programs are needed to address geographical disparities in HPV vaccination.     

Resolution of Novel Human Papillomavirus–induced Warts after HPV Vaccination

Human papillomavirus (HPV) XS2 was isolated from warts on an immunosuppressed patient. After HPV vaccination, the warts resolved. HPVXS2 was also found in warts and normal skin of HIV-positive patients and rarely in HIV-negative controls. Further studies should elucidate the mechanisms that lead to wart clearance.     

Parents’ knowledge,beliefs, acceptance and uptake of the HPV vaccine in members of The Association of Southeast Asian Nations (ASEAN): A systematic review of quantitative and qualitative studies

Background and objectiveCervical cancer is the second most common malignancy affecting females in Southeast Asia. Human Papillomavirus (HPV) vaccines have been available since 2006. Several Association of Southeast Asian Nations (ASEAN) member countries have since introduced and/or piloted the HPV vaccine with adolescent females. This systematic review was conducted to understand what factors influence parents’ acceptance of the HPV vaccine in the region.MethodsSeven databases were searched for qualitative and quantitative studies published up to 16 April 2020. Papers were included if they were peer-reviewed, in English, available in full text, and had a focus on parents’ knowledge, beliefs, attitudes and acceptance of the HPV vaccine. Findings were integrated to answer the review question using framework analysis based on the Theory of Planned Behaviour.ResultsSixteen publications were included and synthesised under the Theory of Planned Behaviour domains: 1) Knowledge, attitudes and acceptance, 2) subjective norms, and 3) perceived behavioural control. Parents’ attitudes to HPV vaccination were positive and acceptance to vaccinate their daughters against HPV was high. The uptake was high when the vaccine was offered for free.ConclusionParents’ acceptance and uptake of the HPV vaccine in ASEAN member-countries was high when the vaccine was offered for free even though their knowledge of cervical cancer and HPV was poor. Further research is needed to see how uptake and acceptance can be maintain when the vaccine is not offered for free.     

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men

BackgroundA nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16–26-year-old men.MethodsParticipants (N = 500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed.ResultsThe HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles.ConclusionsIn addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16–26 years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16–26 years.NCT02114385     

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

Background

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

Methods

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

Findings

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

Interpretation

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

A systematic review of practice-, provider-, and patient-level determinants impacting Asian-Americans’ human papillomavirus vaccine intention and uptake

IntroductionAsian-Americans have been documented to have low human papillomavirus (HPV) vaccine initiation and completion. No research has attempted to examine underlying mechanisms of HPV vaccine uptake disparities among Asian-Americans. Using the P3 (practice, provider, and patient) model, this study aimed to identify practice-, provider-, and patient-level determinants of Asian-Americans’ HPV vaccine intention and uptake.MethodsWe conducted a systematic review of published literature regarding practice-, provider- and patient-level determinants of vaccine intention (e.g., intention, willingness, or acceptability) and uptake (e.g., initiation or completion). Eligible studies were those presenting empirical/original data, focusing on Asian populations in the U.S., including outcomes related to HPV vaccine intention and uptake, and analyzing data on factors associated with these outcomes separately for Asian groups.ResultsTwenty-six studies (19 quantitative and 7 qualitative studies) were included in the review. Most commonly studied subgroups were Koreans (n = 9), Chinese (n = 6), and Cambodians (n = 5). Studies showed varied prevalence across subgroups (intention: 23.4%–72%; initiation: 14%–67%; completion: 9%–63%). Only 3 studies included measurements of practice-level determinants (language services, insurance policy). Twelve studies measured provider-level determinants (most commonly documented: HPV vaccine recommendation). All studies measured patient-level determinants (most commonly documented: HPV and HPV vaccine knowledge, perceived safety, perceived susceptibility, and perceived relationship between HPV vaccine and sexual activity).ConclusionsExisting research on determinants of HPV vaccine intention and uptake among Asian-Americans currently lacks measurements of practice-level constructs and perspectives of clinic staff and providers, which are needed to guide system-level interventions and provider training. Data regarding patient-level determinants suggest that interventions for Asian-American populations can focus on providing educational information in culturally-appropriate manners, leveraging familial influences, and attending to access-related or cultural beliefs about HPV vaccine. Interventions should take into account varied vaccine intention and uptake prevalence in different Asian subgroups.     

癌症患者益处发现干预措施及其效果的系统评价

目的 系统评价癌症患者益处发现干预措施及其效果。方法 计算机检索中国知网(CNKI)、万方、维普、中国生物医学数据库(CBM)、PubMed、Cochrane library、Wiley Online Library、Elsevier ScienceDirect、Springer Link、EBSCO,检索时限为建库至2017年7月,研究类型为随机对照试验。两名研究者独立进行文献筛选、质量评价和资料提取,采用定性方法分析纳入文献的干预措施及其效果。结果 最终纳入9篇RCT研究,采取团体认知行为压力管理疗法共6篇,瑜伽干预共2篇,1篇是中医五行音乐配合肌肉放松训练,均可改善癌症患者的益处发现。结论 纳入的研究均能提高患者益处发现水平,但研究较少,措施复杂,干预者多是心理学专家,国内实施困难,未来需结合我国临床实际情况,构建简单有效,在临床实施可行的益处发现的干预措施。     

Using behavior change frameworks to improve healthcare worker influenza vaccination rates: A systematic review

BackgroundInfluenza vaccination of healthcare workers (HCW) is important for protecting staff and patients, yet vaccine coverage among HCW remains below recommended targets. Psychological theories of behavior change may help guide interventions to improve vaccine uptake. Our objectives were to: (1) review the effectiveness of interventions based on psychological theories of behavior change to improve HCW influenza vaccination rates, and (2) determine which psychological theories have been used to predict HCW influenza vaccination uptake.MethodsMEDLINE, EMBASE, CINAHL, PsycINFO, The Joanna Briggs Institute, SocINDEX, and Cochrane Database of Systematic Reviews were searched for studies that applied psychological theories of behavior change to improve and/or predict influenza vaccination uptake among HCW.ResultsThe literature search yielded a total of 1810 publications; 10 articles met eligibility criteria. All studies used behavior change theories to predict HCW vaccination behavior; none evaluated interventions based on these theories. The Health Belief Model was the most frequently employed theory to predict influenza vaccination uptake among HCW. The remaining predictive studies employed the Theory of Planned Behavior, the Risk Perception Attitude, and the Triandis Model of Interpersonal Behavior. The behavior change framework constructs were successful in differentiating between vaccinated and non-vaccinated HCW. Key constructs identified included: attitudes regarding the efficacy and safety of influenza vaccination, perceptions of risk and benefit to self and others, self-efficacy, cues to action, and social-professional norms. The behavior change frameworks, along with sociodemographic variables, successfully predicted 85–95% of HCW influenza vaccination uptake.ConclusionVaccination is a complex behavior. Our results suggest that psychological theories of behavior change are promising tools to increase HCW influenza vaccination uptake. Future studies are needed to develop and evaluate novel interventions based on behavior change theories, which may help achieve recommended HCW vaccination targets.     

Closure of medical departments during nosocomial outbreaks: data from a systematic analysis of the literature

A total closure of an affected medical department is one of the most expensive infection control measures during investigation of a nosocomial outbreak. However, until now there has been no systematic analysis of typical characteristics of outbreaks, for which closure was considered necessary. This article presents data on features of such nosocomial epidemics published during the past 40 years in the medical literature. A search of the Outbreak Database (1561 nosocomial outbreaks in file) revealed a total of 194 outbreaks that ended up with some kind of closure of the unit (median closure time: 14 days). Closure rates (CRs) were calculated and stratified for medical departments, for causative pathogens, for outbreak sources, and for the assumed mode of transmission. Data were then compared to the overall average CR of 12.4% in the entire database. Wards in geriatric patient care were closed significantly more frequently (CR: 30.3%; P<0.001) whereas paediatric wards showed a significantly lower CR (6.1%; P=0.03). Pathogen species with the highest CR were norovirus (44.1%; P<0.001) and influenza/parainfluenza virus (38.5%; P<0.001). If patients were the source of the outbreak, the CR was significantly increased (16.7%; P=0.03). Infections of the central nervous system were most often associated with closure of the ward (24.2%; P=001). A systematic evaluation of nosocomial outbreaks can be a valuable tool for education of staff in the absence of an outbreak, but may be even more helpful for potentially cost-intensive decisions in the acute outbreak setting on the ward.     

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL^®-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel^® formulations containing MPL^® was evaluated. We conclude that the simple addition of MPL^® to the L2E7 fusion protein already adsorbed onto Alhydrogel^® preferentially enhances antigen specific in vitro T-cell proliferative responses, IFNγ production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.     

Disparities in Human Papillomavirus vaccination coverage among adolescents in Australia: A geospatial analysis

AimThis ecological study aimed to examine the geographic patterns in Human Papillomavirus (HPV) vaccination rates among boys and girls aged 15 years across locations in Australia, in addition to assessing contextual area-level factors that may explain the variations in HPV vaccination coverage.MethodsAggregate HPV vaccination data for Australian girls and boys aged 15 years from 2015 to 16 was obtained from the Australian Institute of Health and Welfare for each Statistical Area level 4 (SA4). A Gradient Boosting Machine learning model was applied to assess the predictors’ importance for the study outcomes. Geographically weighted regression (GWR) models were run to assess whether substantially different relationships between predictors and outcomes occur at different locations in space.ResultsCompleted HPV vaccination across the 88 SA4 regions ranged from 57.6% to 90.6% among girls, and from 53.6% to 85.5% among boys. The 2016 SEIFA Index of Economic Resources was the variable with the highest contribution to the predictions of both girls’ and boys’ HPV vaccination rates. Selected predictors explained 45% and 72% of the geographic variance in vaccination rates among boys and girls, respectively. Normalised coefficients for both GWR models showed a high variation in the associations between predictors and HPV vaccination rates across regions.ConclusionSocioeconomic and education factors were important predictors for HPV vaccination rates among Australian boys and girls aged 15 years, although no variable presented a uniform effect on HPV vaccination across SA4 regions. Important spatial heterogeneity in the effect of predictors was identified across the study area.