Evaluating human papillomavirus vaccination programs

Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of 14,583 dollars per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2% at an incremental cost-effectiveness ratio of 442,039 dollars/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination.     

Randomized controlled trial of two dosing schedules for human papillomavirus vaccination among college age males

Background

Quadrivalent human papillomavirus (HPV) vaccine, for protection against sexually transmitted HPV infection, is licensed for females and males 9–26 years on a 3-dose schedule (0, 2, and 6 months; Standard schedule). Vaccine uptake has been low and catch-up vaccination of older adolescents using an alternate dosing schedule may increase coverage. This study tested the non-inferiority of the immunogenicity of an alternate dosing schedule (0, 2, 12 months) among college age males.

Methods

220 18–25 year old males were randomly assigned to Standard or Alternate schedules. Blood samples were drawn immediately before Dose 1 and 2–6 weeks after Dose 3 and analyzed for antibody titers using a Luminex immunoassay. A value <1.5 for the upper 95% confidence interval (CI) bound of the Standard to Alternate schedule geometric mean titer (GMT) ratio was deemed non-inferior.

Results

Participants averaged 21.3 years old; 19.1% were non-white; completion rate was 93%. The anti-HPV titers for the Alternate schedule group were non-inferior to those of Standard schedule group for all four HPV vaccine virus types. Our results also demonstrated superiority of the Alternate schedule group for all four HPV vaccine virus types.

Conclusion

A delayed third dose at 12 months is immunologically non-inferior and superior for four HPV virus types. Using an alternate dosing schedule offers more flexibility to receive the 3-dose HPV vaccine and may result in higher vaccination rates among college-age males.     

The estimated impact of natural immunity on the effectiveness of human papillomavirus vaccination

BackgroundMathematical modelling is used to estimate the effectiveness of HPV vaccination. These estimates depend strongly on herd immunity and thus on naturally acquired immunity, a mechanism of which little is known. We estimated the impact of different vaccination strategies on HPV-16 and HPV-18 transmission and cervical cancer incidence in the Netherlands, considering different acquired immunity mechanisms.MethodsWe used the STDSIM microsimulation model, and considered two mechanisms for acquired immunity after infection: (I) full immunity with variable duration; (II) cumulatively decreasing susceptibility to reinfection. Girls aged 13–16 years received vaccination (94.7% efficacy for HPV-16 and 92.3% for HPV-18) during a once-off catch-up campaign with 50% coverage, followed by annual vaccination of 12-year-old girls (60% coverage). Alternative vaccination scenarios included increased coverage, including boys, and lower vaccine efficacy.ResultsHPV-16 incidence reduced by 64% under mechanism I and 75% under mechanism II; HPV-18 incidence reduced by 58% and 73%, respectively, and these reductions lead to 48–56% fewer cervical cancer cases. Increasing coverage can lead to over 96% reduction in HPV incidence. Vaccinating boys reduced incidence by 79–89% for HPV-16 and 83–98% for HPV-18 in women.ConclusionsEffectiveness estimates of HPV vaccination differ slightly between different acquired immunity mechanisms, yet these differences are unlikely to affect policy decisions. Offering vaccination to boys as well may be considered to further reduce cancer incidence.     

The association between state Medicaid expansion and human papillomavirus vaccination

Increased vaccination against human papillomavirus (HPV) is recommended to reduce the incidence of anogenital and oropharyngeal cancers. This study aims to evaluate the impact of Medicaid expansion by states on HPV vaccination uptake among adolescents ages 13–17 in the United States. This study analyzed data from the National Immunization Survey (NIS) – Teen from 2011 to 2017 using a cross-sectional design. The adjusted difference-in-difference estimate of Medicaid expansion on HPV vaccine initiation was statistically significant (β = 0.031, 95% CI [0.016, 0.046]). There were significant increases in HPV vaccination after states expanded their Medicaid program. The largest increase occurred in those individuals below the federal poverty level and a modest increase occurred in those above the federal poverty level but below $75,000 of annual family income. Further research should be conducted to analyze the combined effect of multiple policies on HPV vaccination.     

青春前期女性接种人乳头瘤病毒疫苗专家共识

人乳头瘤病毒（HPV）疫苗接种是子宫颈癌防控的重要措施之一。通过综合考虑HPV疫苗接种的有效性、安全性、成本效益等多方面因素,专家强烈推荐青春前期（9~14岁）女性作为重点目标人群应优先接种HPV疫苗,提高重点目标人群HPV疫苗免疫覆盖率,以达到子宫颈癌一级预防策略的最佳效果。     

The cost-effectiveness of human papillomavirus vaccination in the Philippines

Cervical cancer is the second most common cancer among women in the Philippines. Human papillomavirus (HPV) vaccination provides protection from the most common cancer-causing HPV types. This analysis used a proportionate outcomes model to estimate the potential cost-effectiveness of four different HPV vaccine products—Cervarix?, Cecolin®, GARDASIL®, and GARDASIL®9—for routine HPV vaccination of 10 cohorts of 9-year-old girls from the government and societal perspectives. Model parameters included cervical cancer burden, healthcare and program costs, vaccine efficacy with and without potential cross-protection, and vaccination coverage. Univariate and probabilistic sensitivity analyses evaluated the impact of uncertainty on model results. Compared to no vaccination, HPV programs with Cecolin®, Cervarix?, and GARDASIL® are projected to be cost-effective at US$1,210, US$1,300, and US$2,043 per DALY averted, respectively, from the government perspective, and at US$173, US$263, and US$1,006 per DALY averted, respectively, from the societal perspective when cross-protection was considered. When direct comparisons were made across vaccines, GARDASIL® was dominated by Cervarix? and Cecolin®. In a scenario where cross-protection was not considered, results were similar except that Cervarix? and GARDASIL® were both dominated by Cecolin®. GARDASIL®9 was not cost-effective under any of the modeled scenarios.     

Cost-effectiveness analysis of a gender-neutral human papillomavirus vaccination program in the Netherlands

BackgroundVaccinating girls against human papillomavirus (HPV) infection is a highly effective and cost-effective intervention to provide protection against HPV-induced cancers. Since vaccination coverage rates among girls is modest in the Netherlands, additional strategies should be implemented to improve the protection against HPV-related cancer. Here we assessed the benefits and cost-effectiveness of gender-neutral vaccination.MethodsWe designed a static Markov model with a lifelong time horizon to simulate a cohort of 100,000 12-year-old Dutch boys. The model compares health and economic effects of HPV vaccination taking the current female vaccination coverage into consideration. HPV prevalence in boys was corrected for the predicted herd effects of the female programme in 2017. We extracted transition probabilities from peer-reviewed literature and previously constructed models. The robustness of the model was tested with multiple sensitivity analyses.ResultsVaccinating 30% of 100,000 12-year-old boys prevents 18, 13 and 25 cases of anal, penile, and oropharyngeal cancers in men, respectively. A total of 205 quality-adjusted life-years (QALYs) are saved by preventing cancer-related morbidity and mortality. Assuming a vaccine price of €50 per dose, the incremental cost-effectiveness ratio (ICER) is €17,907 per QALY. In addition, due to vaccine-induced herd effects, we estimated that 110 cases of cancer in females would be additionally prevented and 246 QALYs would be gained in the female cohort, bringing the total to 166 cancers prevented and 451 QALYs gained. Taking these additional benefits of boys’ vaccination into account, the overall ICER was estimated at €7310 per QALY gained. The model outcomes are most sensitive to variation in vaccine price, herd immunity from females and vaccine efficacy.ConclusionsVaccination of boys, additional to girls, will prevent a relevant number of cancers in both boys and girls. Based on the current Dutch situation vaccination of HPV in boys is likely cost-effective.GSK Study identifier: HO-18-19169. A graphical abstract and supplementary data to this article can be found online at https://doi.org/10.1016/j.vaccine.2020.05.031.     

Singaporean men's knowledge of cervical cancer and human papillomavirus (HPV) and their attitudes towards HPV vaccination

Little is known of men's knowledge of cervical cancer and its links with human papillomavirus (HPV), or of their attitudes and beliefs about HPV vaccination. This is despite men's sexual behaviour contributing to HPV transmission and their potential role in deciding whether their children are vaccinated against HPV. To address this, a comprehensive survey was conducted in Singapore where plans are underway for an HPV vaccination program. A representative sample of 930 Singaporean men was found to have moderate knowledge of cervical cancer but poor knowledge and awareness of HPV. Although these men showed strong support for HPV vaccination, overall findings highlight the importance of including men in education campaigns that aim to decrease the incidence of cervical and other HPV-related cancers and to increase the uptake of HPV vaccination.     

Female human papillomavirus (HPV) vaccination: Global uptake and the impact of attitudes

Human papillomavirus (HPV) is the causative agent in cervical cancer and has been implicated in a range of other malignancies. Preventative vaccines are now internationally available and provide high levels of protection from common viral strains. The introduction of a comprehensive vaccination programme (except ‘program’ in computers) could prevent over 60% of current cervical cancer cases, but this is dependent on such programmes achieving a high level of coverage. In this review, we summarise the current trends in female HPV vaccination coverage throughout the world, and place it in the context of available research on attitudes towards vaccination amongst the public and health professionals.     

广东省某医药院校大学生人乳头瘤病毒疫苗接种意愿调查

目的了解广东省某医药院校大学生对人乳头瘤病毒(HPV)及HPV疫苗的认知情况、态度及HPV疫苗接种意愿,为HPV疫苗在国内推广接种提供建议。方法采用分层整群抽样法选取301名广东省某医药院校全日制本科在校学生,使用自填式网络问卷调查。对HPV及HPV疫苗认知度进行描述统计,采用X²检验和二分类非条件logistics回归分析影响HPV疫苗接种意愿的因素。结果 53.96%的调查对象知道HPV;46.97%的男生和53.77%的女生知道HPV疫苗;72.73%的男生和75.94%的女生有HPV疫苗接种意愿。婚姻状态(OR=2.143,P=0.009)、宫颈癌筛查知晓度(OR=1.805,P=0.018)、患宫颈癌可能性自我评价(OR=0.641,P=0.024)、是否同意HPV疫苗能有效预防宫颈癌(OR=1.919,P=0.027)以及是否同意疫苗能有效预防疾病(OR=1.686,P=0.022)影响HPV疫苗接种意愿。结论被调查大学生对HPV疫苗认知度高,接种HPV疫苗的意愿强。建议学校和社会加大对HPV及HPV疫苗宣传力度,政府加强疫苗监管。     

Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom

Many countries are considering vaccination against human papillomavirus (HPV). However, the long-term impact of vaccination is difficult to predict due to uncertainty about the prevalence of HPV infection, pattern of sexual partnerships, progression of cervical neoplasias, accuracy of screening as well as the duration of infectiousness and immunity. Dynamic models of human papillomavirus (HPV) transmission were developed to describe the infection spread and development of cervical neoplasia, cervical cancer (squamous cell and adenocarcinoma) and anogenital warts. Using different combinations of assumptions, 9900 scenarios were created. Each scenario was then fitted to epidemiological data and the best-fitting scenarios used to predict the impact of vaccination. Results suggest that vaccinating 12-year-old girls at 80% coverage will result in a 38–82% reduction in cervical cancer incidence and 44–100% reduction in anogenital warts incidence after 60 years of an ongoing vaccination programme if vaccine protection lasts 20 years on average. The marginal benefit of vaccinating boys depends on the degree of protection achieved by vaccinating girls.     

Decline in vaccine-type human papillomavirus prevalence in young men from a Midwest metropolitan area of the United States over the six years after vaccine introduction

PurposeThe aim of this study was to determine changes in human papillomavirus (HPV) prevalence among young men from a Midwest metropolitan area over the six years after vaccine introduction, including HPV prevalence in men overall, in vaccinated men to examine vaccine impact and in unvaccinated men to examine herd protection. An exploratory aim was to examine associations between number of vaccine doses and HPV prevalence.MethodsMen aged 14–26 years reporting male-female and/or male-male sexual contact were recruited from a primary care clinic, sexually transmitted disease clinic, and community setting during two waves of data collection: 2013–2014 (N = 400) and 2016–2017 (N = 347). Participants completed a questionnaire and were tested for penile, scrotal and anal HPV. Changes in prevalence of any (≥1 type) and vaccine-type HPV (HPV6, 11, 16, and/or 18) were examined using propensity score weighted logistic regression. Associations between number of doses and HPV infection were determined using chi-square tests and logistic regression.ResultsThe proportion of men with a history of ≥1 HPV vaccine doses increased from 23% to 44% (p < 0.001) from waves 1 to 2. After propensity score weighting, infection with ≥1 vaccine-type HPV significantly decreased among all men (29% to 20%; 31% decrease; odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.44–0.88) and unvaccinated men (32% to 21%; 36% decrease; OR = 0.56, 95%CI = 0.34–0.86); there was a non-significant decrease (21%) among vaccinated men. Associations between number of doses and HPV prevalence were not statistically significant.ConclusionsPrevalence of vaccine-type HPV decreased among all, vaccinated, and unvaccinated men six years after HPV vaccine recommendation, supporting vaccine impact and herd protection. Decreases in vaccine-type HPV in all men appear to be due to decreases in unvaccinated men, suggesting that the full impact of vaccination has yet to be realized. Continued monitoring and efforts to vaccinate men prior to sexual initiation are warranted.     

深圳地区某女性体检人群人乳头瘤病毒感染现状及宫颈细胞学异常研究

目的:利用深圳地区女性体检人群数据,了解人群HPV感染及宫颈液基薄层细胞学检查（TCT）异常情况。方法:采用横断面研究设计,利用2018年深圳地区女性体检人群HPV感染及TCT数据,描述和分析HPV感染及TCT检测结果。结果:共有75 754名≥18岁女性纳入HPV感染率分析、103 508名≥18岁女性纳入TCT分析...     

Planning for human papillomavirus (HPV) vaccination in sub-Saharan Africa: A modeling-based approach

Background

Human papillomavirus (HPV) vaccines have the potential to reduce cervical cancer incidence and mortality, particularly in the parts of the developing world that bear the greatest burden of disease. This research sought to predict the impact and cost-effectiveness of an HPV vaccination program in an example low-resource country with a high burden of cervical cancer: Mali, West Africa.

Methods

Novel compartmental mathematical models projected the impact of adolescent HPV vaccination in urban and rural areas of Mali. The models accounted for two high-risk vaccine-types: HPV 16 and 18. We then attached comprehensive real cost and cost-effectiveness estimates.

Results

Our models predict that HPV vaccination in Mali will reduce cervical cancer burden by a factor roughly equal to vaccine coverage. A point vaccination program was simulated in a cohort of 333,146 urban and 588,982 rural Malian women, age 10–14. Vaccination of 50% of girls reduced the peak prevalence of HPV 16/18 to 5.0% in the urban setting and 9.6% in the rural setting, down from 11.7% and 22.0%, respectively, with no vaccination. The 50% vaccination scenario averted 1145 cervical cancer deaths in the urban group and 2742 in the rural group. The cost per discounted life-year saved in this scenario was 1030 US dollars (urban) and 725 dollars (rural). The cost per life-year saved was higher at 90% coverage, but was still in the range of a “cost-effective” public health intervention.

Conclusions

This research yielded the most comprehensive real cost estimates of HPV vaccination yet published for sub-Saharan Africa. Our models indicate that HPV vaccination in Mali will be cost-effective when introduced. To maximize the benefit using limited resources, vaccination programs may begin with a target coverage of about 50%. We anticipate that costs of reaching late adopters after the First Vaccinated Wave of vaccination will be higher, but worthwhile.     

Effectiveness of ‘catch-up’ human papillomavirus vaccination to prevent cervical neoplasia in immunosuppressed and non-immunosuppressed women

It is unknown whether the HPV vaccine is effective in immunocompromised women during catch-up ages. We performed a case-control study of 4,357 women with incident CIN2+ (cases) and 5:1 age-matched, incidence-density selected controls (N = 21,773) enrolled in an integrated health care system from 2006 to 2014. Vaccine effectiveness was estimated from multivariable conditional logistic regression models, with results stratified by immunosuppression history, defined as prior HIV infection, solid organ transplant history, or recently prescribed immunosuppressive medications. HPV vaccination resulted in a 19% reduction in CIN2+ rates for women without an immunosuppression history but a nonsignificant 4% reduction for women with an immunosuppression history. Further research is needed to evaluate whether catch-up HPV vaccine effectiveness varies by immunosuppression status, especially given the recent approval of the HPV vaccine for adults up to 45 years of age.     

Knowledge differences between male and female university students about human papillomavirus (HPV) and cervical cancer: Implications for health strategies and vaccination

Knowledge about HPV and cervical cancer (CC) depends on several factors such as gender and education, which brings implications for health strategies and vaccination. A survey was conducted in Portugal with a representative sample of 1706 university students. Only 55.4% (n = 945) had already heard of HPV, although 88.3% (n = 834) from that know that is a risk factor for CC. 89% students (n = 841) wants to be vaccinated against it, but only 13.8% stated as main reason to be vaccinated “prevention of the disease”. Mean scores of knowledge were calculated. Statistical differences were found, regarding “CC knowledge”, in gender (p < 0.001) and between health sciences schools and non-health sciences schools (p < 0.001). Differences regarding the study area in “knowledge and beliefs of HPV” (p < 0.001) and in “relation between HPV and CC” (p < 0.001) were found. Therefore, these differences may help to develop effective strategies that lead to decline CC incidence and mortality.     

Impact of introduction of the 9-valent human papillomavirus vaccine on vaccination coverage of youth in North Carolina

ObjectivesThe objective of this study was to evaluate the impact of introduction of 9vHPV vaccine on HPV vaccination uptake (doses per capita) and initiation (≥1 doses), completion (≥3 doses) and compliance (≥3 doses within 12 months) by adolescents.MethodsWe used a retrospective cohort analysis using North Carolina Immunization Registry (NCIR) data from January 2008 through October 2016. The sample included Vaccines for Children eligible adolescents aged 9 to 17 years in 2016, for whom the NCIR contains complete vaccination history. We applied an interrupted time series design to measure associations between ZIP Code Tabulation Area (ZCTA)-level HPV vaccination outcomes over time with the introduction of 9vHPV in North Carolina (NC) in July 2015.ResultsEach outcome displayed a linear upward trend over time with large seasonal spikes near August of each year, corresponding to the time when adolescents often receive other vaccines required for school entry. After accounting for these underlying trends, introduction of 9vHPV was not associated with a change in publicly funded HPV vaccination rates in NC.ConclusionsOur results indicate that 9vHPV substituted for 4vHPV in the first year after release in NC, but the release of 9vHPV was not associated with an overall change in HPV vaccination.     

Clinical effectiveness and cost-effectiveness of quadrivalent human papillomavirus vaccination in HIV-negative men who have sex with men to prevent recurrent high-grade anal intraepithelial neoplasia

We examined the long-term clinical and economic benefits of quadrivalent human papillomavirus (qHPV) vaccine as a secondary/adjunct prevention strategy in the prevention of recurrent high-grade intraepithelial neoplasia (HGAIN) in HIV-negative men who have sex with men (MSM) and are 27 years or older. We constructed a Markov model to evaluate the clinical effectiveness and cost-effectiveness of two strategies: (1) no qHPV vaccine after treatment for HGAIN versus (2) qHPV vaccine after treatment for HGAIN. Model parameters, including natural history of anal cancer, vaccine efficacy measured in terms of hazard ratio (HR) (decrease in the risk of recurrent HGAIN), HGAIN treatment efficacy, utilities, and costs, were obtained from the literature. The outcomes were measured in terms of lifetime risk of anal cancer, lifetime cost, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted on all model parameters. We found that vaccinating HIV-negative MSM reduced the lifetime risk of anal cancer by 60.77% at an ICER of US$87,240 per quality-adjusted life-year. The results were highly sensitive to vaccine efficacy, transition of HGAIN to anal cancer, cost of treatment for HGAIN, vaccine degree of protection over time, and the vaccine duration of protection and less sensitive to HPV clearance, cost of qHPV vaccine, and the transitions from normal to low-grade anal intraepithelial neoplasia (LGAIN) and normal to HGAIN. With an HR of 0.3, the ICER was well below a $50,000 willingness-to-pay threshold; with an HR of 0.5, the ICER was still below a threshold of $100,000. The most critical disease-related factor influencing the cost-effectiveness was the progression of HGAIN to anal cancer. At an annual transition probability below 0.001, the ICER was below $50,000. Vaccinating HIV-negative MSM treated for HGAIN decreases the lifetime risk of anal cancer and is likely to be a cost-effective intervention.     

Can high overall human papillomavirus vaccination coverage hide sociodemographic inequalities? An ecological analysis in Canada

BackgroundHuman papillomavirus (HPV) vaccination programs have been implemented in more than 50 countries. These programs offer tremendous promise of reducing HPV-related disease burden. However, failure to achieve high coverage among high-risk groups may mitigate program success and increase inequalities. We examined sociodemographic inequalities in HPV vaccination coverage in 4 Canadian provinces (Quebec (QC), Ontario (ON), Manitoba (MB), British Columbia (BC)).MethodsWe obtained annual HPV vaccination coverage of pre-adolescent girls at provincial and regional levels, from the start of programs to 2012/2013. Regions refer to administrative areas responsible for vaccine implementation and monitoring (there are 18/36/10/16 regions in QC/ON/MB/BC). We obtained regions’ sociodemographic characteristics from Statistics Canada Census. We used univariate weighted linear regression to examine the associations between regions’ sociodemographic characteristics and HPV vaccination coverage.ResultsProvincial HPV vaccination coverage is generally high (QC:78%; ON:80%; MB:64%, BC:69%, 2012/13). QC had the highest provincial vaccination coverage since the program start, but had the greatest inequalities. In QC, regional HPV vaccination coverage was lower in regions with higher proportions of socially deprived individuals, immigrants, and/or native English speakers (p < 0.0001). These inequalities remained stable over time. Regional-level analysis did not reveal inequalities in ON, MB and BC.ConclusionSchool-based HPV vaccination programs have resulted in high vaccination coverage in four Canadian provinces. Nonetheless, high overall coverage did not necessarily translate into equality in coverage. Future work is needed to understand underlying causes of inequalities and how this could impact existing inequalities in HPV-related diseases and overall program success.