Expert Review of Vaccines

Cost-effectiveness of human papillomavirus vaccination among girls aged 9–16 years in China: a meta-analysis

Imported 2 v, 4 v, and 9vHPV vaccines are costly in China, whereas the domestic 2vHPV is more affordable. This study aimed to summarize cost-effectiveness evidence by pooling the incremental net monetary benefit (INB) of HPV vaccination for girls in China. We searched PubMed, Embase®, Web of Science, and Cochrane databases from inception to 18 January 2024, for cost-effectiveness analyses of 2vHPV, 4vHPV, and 9vHPV vaccines compared to no HPV vaccination (NoV) and to each other. All monetary units were adjusted to 2022 US dollars. INBs were calculated as the difference in incremental effectiveness multiplied by the willingness-to-pay threshold minus the incremental cost and pooled by vaccine type using random-effects or fixed-effects models. Sixteen studies involving 61 comparisons were included. The INBs (95% CI) for domestic 2vHPV, imported 2vHPV, 4vHPV, and 9vHPV vaccines, compared to NoV, were USD 569.99 (58.62, 1081.36), 186.39 (86.21, 286.57), 239.14 (142.46, 335.81), and 298.41 (198.31, 398.51), respectively. HPV vaccines were significantly cost-effective compared to NoV. 4vHPV vaccine was less cost-effective than imported 2vHPV vaccine, with an INB of USD - 693.98 (-1062.17, -325.79). HPV vaccines were cost-effective compared to NoV in China. Our findings would facilitate policy-making of HPV immunization programs.

Readiness assessment for cervical cancer elimination and prevention of human papillomavirus (HPV)-related cancers in Europe – are we winning the RACE?

To address the cervical cancer burden globally, the World Health Organization and European Union released strategies to facilitate HPV-related cancers prevention, including cervical cancer elimination. This research assessed European country level readiness to achieve cervical cancer elimination by adhering to such strategies. Readiness for cervical cancer elimination was assessed across a range of guiding questions relevant to three defined key domains: vaccination, screening, and treatment, each with two sub-domains focusing on decision making and implementation efforts. Publicly available data sources were used to inform the scoring across domains, to tier countries into either high, moderate-high, moderate-low, and low readiness archetypes.Key parameters identified associated with the high readiness archetype were high vaccination coverage rates (>70%), availability of gender neutral and catch-up vaccination, school-based vaccination availability, organized screening programs, use of HPV DNA primary screening tests, and data surveillance. Our analysis highlights significant variability in decision making and implementation of vaccination, screening, and treatment programmes across Europe. Country scores expose the need for a multifaceted approach to achieve cervical cancer elimination in Europe, encompassing solid decision making commitments, implementation of these commitments, and the ability to collect, surveil, and apply the data use accurately.

Cost-effectiveness of nonavalent HPV vaccination in the Netherlands

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

In 30 years, gender-neutral vaccination eradicates oncogenic human papillomavirus (HPV) types while screening eliminates HPV-associated cancers

HPV vaccine introduction in the Americas: a decade of progress and lessons learned

Human papillomavirus (HPV) is an important public health concern due to its causative role in many cancers, especially cervical cancer, and other conditions that lead to serious health consequences in both men and women. In Latin America and the Caribbean, nearly 60,000 new cases of cervical cancer and another 7,000 HPV-associated cancers are diagnosed annually. HPV vaccination combined with comprehensive cervical cancer control programmingis paving the way for eliminating cervical cancer as a major public health problem and drastically reducing other HPV-associated diseases. To date, 44 countries and territories in the Americas have introduced HPV vaccines as part of their national immunization programs and cervical cancer control strategies. Early lessons from HPV vaccine introduction suggest that transparent and credible evidence-based decision-making, information, education and communication about HPV and cervical cancer, coordination with existing cervical cancer control initiatives, and precise planning for ensuring effective uptake of the vaccine in target groups are all critical elements of success. There is an urgent need for strategies to increase HPV vaccine coverage, and as the integrated control programs evolve and other HPV-associated disease becomes important for public health, there will be a need for continued program and policy evaluation.

Don’t jump down my throat: gender gap in HPV vaccinations risk long term cancer threats

HPV is the most common sexually transmitted disease in the United States, the principal cause for cervical cancer, and the principal cause for the recent increase in head and neck squamous cell cancers. Current interventions and research goals fail to sufficiently address the need to prevent HPV, and continued stigmatization of HPV as a female disease further discourages young patients from seeking the vaccine. This paper will review the epidemiology of HPV, including the rise in male cases and cancers, the immunogenicity of the vaccine, results of efficacy and effectiveness trials, and the social and operational challenges to preventing HPV infection within the United States. Statistics were sourced from the CDC. Studies were found through PubMed searches related to HPV. Priority was given to articles published in the last ten years, and policy statements from major associations were considered. To improve vaccination rates, diversified physician engagement in vaccinating adolescents, better knowledge sharing about vaccine hesitancy, and specifically targeting males to bridge the gender gap are all necessary. Further, childhood HPV vaccinations and therapeutic vaccinations remain under-researched but potentially effective methods to diminish the incidence of HPV-associated cancers.

Global status of HPV vaccination two decades in: effective, safe and preventing cancer

Prophylactic human papillomavirus vaccines have been in use in populations worldwide for nearly 20 years. Much has been learnt in relation to their effectiveness, safety, and how best to effectively implement them in populations to prevent cancer and other HPV-related diseases. Global challenges such as limited supply and the mismatch between those who can afford them and those with the greatest disease burden from cervical cancer have prevented optimal usage to date. Here we identified recent papers and focus upon the accumulated evidence regarding HPV vaccine: i) effectiveness in preventing cancer and precancerous lesions, ii) safety in population usage, iii) trial evidence supporting registration of four newer vaccines, iv) progress in country-level introductions and coverage, and v) lessons learned in effective implementation. Reasons for optimism are many, with vast cumulative knowledge on impact, safety and implementation and accelerating HPV vaccine introductions, simplification of delivery and reduced costs through single dose approaches and supply constraints easing. However, considerable challenges remain in achieving and maintaining high and equitable global coverage, given the uncertainty in funding, risk to ongoing prioritization of health equity and to vaccine confidence in the current global public health environment.

Comparative efficacy of human papillomavirus vaccines: systematic review and network meta-analysis

Despite their use, differences in human papillomavirus (HPV) vaccine efficacies remain uncertain. This study assesses efficacy differences among bivalent, quadrivalent, and nine-valent HPV (2vHPV, 4vHPV, and 9vHPV) vaccines. PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials comparing HPV vaccine efficacy against persistent infection (≥6 months) and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Network meta-analysis yielded direct and indirect comparisons. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were reported, and robustness was evaluated via sensitivity analysis. In 11 randomized controlled trials with 58,881 healthy women, for persistent infection with HPV 16, 9vHPV was most effective at 97% (RR = 0.03, 95% CI: 0.01-0.08); for HPV 18, 2vHPV (Cecolin) was most effective at 98% (RR = 0.02, 95% CI: 0.00-0.29); for CIN2+ associated with HPV 16 and 18, 4vHPV was most effective at 99% (RR = 0.01, 95% CI: 0.00-0.10) and 97% (RR = 0.03, 95% CI: 0.00-0.45), respectively; for persistent infection with HPV 31, 33, 45, 52, and 58, 9vHPV was ≥ 95% effective; both 2vHPV vaccines were cross-effective against HPV 31, 33, and 45; and 4vHPV was cross-effective against HPV 31. HPV vaccine efficacies differ for different HPV types. Additional data are needed to determine the cross-efficacy of 2vHPV (Cecolin).

Estimating the time required to reach HPV vaccination targets across Europe

Cervical cancer (CC) is one of the most common causes of cancer-related deaths in women. The World Health Organization (WHO) has called for the CC elimination as a public health priority and has urged countries to achieve a 90% vaccine coverage rate of human papilloma virus (HPV) vaccination among 15-year-old girls by 2030. Regression models were fitted to the WHO HPV vaccine coverage rate data to estimate when the 90% vaccine coverage rate target would be achieved in 22 European countries. The mean vaccine coverage rate of included countries was 62.2% (SD: 18.3). Nine countries (Iceland, Norway, Portugal, Ireland, Hungary, Spain, Sweden, Denmark, and Switzerland) are expected to achieve a 90% vaccine coverage rate by 2030. Six countries (Estonia, Cyprus, Netherlands, France, Germany, and Italy) are expected to reach a 90% vaccine coverage rate between 2030 and 2040, whereas seven countries (Belgium, Bulgaria, Finland, Latvia, Luxembourg, Malta, and Slovenia) are not expected to achieve the 90% vaccine coverage rate target by 2040. The majority of European countries are not on track to achieve 90% vaccine coverage rate by 2030. To achieve this, a significant increase in the annual vaccine coverage rate growth rate is required.