Global estimates of expected and preventable cervical cancers among girls born between 2005 and 2014: a birth cohort analysis.

BACKGROUND: WHO has launched an initiative aiming to eliminate cervical cancer as a public health problem. Elimination is a long-term target that needs long-lasting commitment. To support local authorities in implementing human papillomavirus (HPV) vaccination, we provide regional and country-specific estimates of cervical cancer burden and the projected impact of HPV vaccination among today's young girls who could develop cervical cancer if not vaccinated. METHODS: The expected number of cervical cancer cases in the absence of vaccination among girls born between 2005 and 2014 was quantified by combining age-specific incidence rates from GLOBOCAN 2018 and cohort-specific mortality rates by age from UN demographic projections. Preventable cancers were estimated on the basis of HPV prevalence reduction attributable to vaccination and the relative contribution of each HPV type to cervical cancer incidence. We assessed the number of cervical cancer cases preventable through vaccines targeting HPV types 16 and 18, with and without cross-protection, and through vaccines targeting HPV types 16, 18, 31, 33, 45, 52, and 58. FINDINGS: Globally, without vaccination, the burden of cervical cancer in these birth cohorts is expected to reach 11·6 million (95% uncertainty interval 11·4-12·0) cases by 2094. Approximately 75% of the burden will be concentrated in 25 countries mostly located in Africa and Asia, where the future number of cases is expected to increase manyfold, reaching 5·6 million (5·4-6·0) cases in Africa and 4·5 million (4·4-4·6) cases in Asia. Worldwide immunisation with an HPV vaccine targeted to HPV types 16 and 18, with cross-protection against HPV types 31, 33, and 45, could prevent about 8·7 million (8·5-9·0) cases. INTERPRETATION: Detailed estimates of the increasing burden of cervical cancer and projected impact of HPV vaccination is of immediate relevance to public health decision makers. Shifting the focus of projections towards recently born girls who could develop cervical cancer if not vaccinated is fundamental to overcome stakeholders' hesitancy towards HPV vaccination. FUNDING: Bill & Melinda Gates Foundation, Canadian Institutes of Health Research.

Human papillomavirus vaccination in immigrants and descendants of immigrants in Denmark.

OBJECTIVE: In Denmark, human papillomavirus (HPV) vaccination has been offered at age of 12 to girls born in 1996 and later. In this cohort study, we examined routine HPV vaccination uptake in immigrants and descendants from different countries and regions compared with native Danes, including the influence of socioeconomic characteristics and potential changes in uptake by birth cohort. METHODS: In nationwide registers, we identified all girls born in 1996-2003 (n = 260 251) and obtained information on country of origin, HPV vaccinations and parents' income and employment. Vaccination was defined as receiving ≥1 dose within 2 years after eligibility for routine vaccination. Odds ratios (ORs) were estimated by logistic regression separately for birth cohorts 1996-2000 and 2001-2003. RESULTS: Uptake in immigrants and descendants varied by country and region of origin. Overall, immigrants had lower uptake than native Danes, in birth cohorts 1996-2000 [79% vs. 93%, OR = 0.31; 95% confidence interval (CI), 0.29-0.34] and 2001-2003 (63% vs. 73%, OR = 0.60; 95% CI, 0.54-0.66). Descendants had lower uptake than native Danes in cohorts 1996-2000 (89% vs. 93%, OR = 0.65; 95% CI, 0.60-0.68), but higher uptake in cohorts 2001-2003 (76% vs. 73%, OR = 1.15; 95% CI, 1.08-1.21). Most associations were attenuated, but not entirely explained, when adjusting for socioeconomic characteristics. CONCLUSION: HPV vaccination uptake varied by country and region. Most immigrants had lower uptake than native Danes, and in most groups, this was not fully explained by socioeconomic differences. Patterns in descendants were mixed. Interventions to increase uptake should be tailored to specific groups of immigrants/descendants.

Human Papillomavirus Vaccine Interventions in the U.S.: A Systematic Review and Meta-analysis.

CONTEXT: Despite current recommendations, human papillomavirus vaccine uptake remains low. A systematic review and meta-analysis assessed the effectiveness of interventions targeting human papillomavirus vaccine initiation and completion among children, adolescents, and young adults aged 9-26 years. EVIDENCE ACQUISITION: Three electronic databases (CINAHL, OVID, and Web of Science) were searched for articles published in English peer-reviewed journals between January 2006 and January 2017 of U.S. studies that evaluated intervention strategies and reported post-intervention human papillomavirus vaccine initiation or completion rates among individuals aged 9-26 years. Study characteristics and outcomes were extracted. Data were collected in 2016 and analyzed in 2017. EVIDENCE SYNTHESIS: Reviewers screened 983 unique titles and abstracts, read 241 full-text articles, and extracted data from 30 articles meeting the inclusion criteria (12 behavioral, ten environmental, four informational, and four combination strategies). Published EQUATOR (Enhancing the Quality and Transparency of Health Research) guidelines were used to assess study quality. Random effects meta-analyses were conducted. The meta-analyses included 17 RCTs and quasi-experiments involving 68,623 children, adolescents, and young adults. The pooled relative incidence estimates were 1.84 (95% CI=1.36, 2.48) for human papillomavirus vaccine initiation and 1.50 (95% CI=1.23, 1.83) for completion. Behavioral and informational interventions doubled human papillomavirus vaccine initiation (relative incidence estimate=2.04, 95% CI=1.36, 3.06 and relative incidence estimate=1.92, 95% CI=1.27, 2.91, respectively). Behavioral interventions increased completion by 68% (relative incidence estimate=1.68, 95% CI=1.25, 2.27). CONCLUSIONS: Evidence supports behavioral interventions for increasing human papillomavirus vaccine initiation and completion. Future studies are needed to assess the effectiveness of interventions in reaching diverse populations and reducing missed opportunities for human papillomavirus vaccination.

[Vaccination: What's new?] / Impfungen: Was ist neu?

Vaccination practices in Germany are driven by scientific developments and a complex regulatory environment. Some important developments in 2018 are described here: Starting in 2018 only quadrivalent influenza vaccines will be used for the seasonal vaccination. Despite the availability of meningococcus ACWY and B vaccines and their use in other countries only the type C conjugate vaccine will be used for the routine vaccination of children. For the first time there is now an official recommendation to also vaccinate boys against HPV using either the bivalent or the nonavalent vaccine. After promising trial results a timely guideline for the use of the newly available adjuvanted subunit zoster vaccine is to be expected. Negative trial results mark a major setback for the development of a CMV vaccine. While only developed during the 2013 - 16 outbreak a highly effective Ebola vaccine is already being distributed to fight the current Congo outbreak.

On surmounting the barriers to HPV vaccination: we can do better.

The major impediment to increased human papillomavirus (HPV) vaccination coverage in young males and females is lack of health care provider recommendation. Despite its efficacy in preventing cervical cancer, HPV vaccination in females (49.5%) and males (37.5%) ages 13 through 17 falls well below the Centers for Disease Control and Prevention's (CDC) Healthy People 2020 target of 80% coverage. Parents' willingness to vaccinate their child has been shown to be much higher when physicians share personal vaccination decisions for their own children as well as what other parents have done at that particular clinic. Furthermore, the vaccine must be presented presumptively as a "bundle" along with the rest of the standard adolescent vaccine panel. Multiple exemplars presented including in several European countries, low-income countries and Rwanda, demonstrate that school-based health care systems dramatically increase vaccination coverage. Finally, acceptability for vaccination of males must improve by increasing provider recommendation and by presenting the HPV vaccine as a penile, anal and oropharyngeal cancer prevention therapy in males and not merely a vaccine to prevent cervical cancers in females. Paediatricians, obstetrician/gynaecologists and primary care physicians should consider these data as a call-to-action. Key messages • Despite recent efforts in the US, only 49.5% of females and only 37.5% of males ages 13 through 17 have received all recommended HPV vaccine doses. These numbers fall well below the 80% target set forth by the Healthy People 2020 initiative. • According to the CDC, if health care providers increase HPV vaccination rates in eligible recipients to 80%, it is estimated that an additional 53,000 cases of cervical cancer could be prevented during the lifetime of those younger than 12 years. Furthermore, for every year that the vaccination rate does not increase, an additional 4400 women will develop cervical cancer. • First and foremost, healthcare providers (HCPs) must make a strong recommendation to vaccinate patients and these recommendations must become routine, including for males. • It is clear that HPV vaccination rates improve significantly when vaccine administration occurs at designated, well-organized sites such as school-based vaccination programmes. Furthermore, HPV vaccination should be a high school requirement and offered in the standard adolescent vaccine panel as a bundle with Tdap and MenACWY vaccines in order to promote maximum adherence. • Finally, research on immunogenicity and antibody titre longevity needs to be done in newborns. The HPV vaccine may be recommended in the newborn panel of vaccines to avoid any issues of sexualization and misplaced fears of sexual disinhibition, akin to the success of the Hepatitis B vaccine in the 1980s. • The HPV vaccine is a vaccine against cancer and should be aggressively marketed as such. As healthcare providers, we need to make every effort to overcome barriers, real or perceived, to protecting our population from potential morbidity and mortality associated with this virus.

[One decade of HPV vaccination in Germany]. / Ein Jahrzehnt der HPV-Impfung in Deutschland.

As a worldwide very common sexually transmitted infection (STI), HPV causes millions of genital warts every year and is responsible for 5% of all cancers in men and women. With strong empirical evidence for both vaccine safety and efficacy, the HPV vaccines proved to protect against these HPV-related conditions over the last decade. But current HPV vaccination coverage is suboptimal in many countries. Even in Germany the absence of a school-based immunization program and the recommendation of a publicly funded girls-only HPV vaccination strategy are the main reasons for a female coverage rate under 40%, which does not achieve herd immunity for the boys. Therefore, the German immunization program urgently needs revision to fight an increasing number of young Germans missing out on the most important development in cancer prevention. Gender-neutral bundling of the HPV vaccine to other routinely recommended vaccines for preteens at one visit will have many advantages at the same time: Lowering the age of HPV vaccination to 9-12 years will improve the cost-effectiveness because a two-dose vaccination schedule is established on this score. Time-consuming and redundant explanations of the attending physician as well as parent's discussion on feeling stigmatized by the STI nature of HPV could be avoided in a combined vaccination setting. By expanding the HPV vaccination to boys, the resulting gender-neutral vaccination program can be cost-effective if all HPV-related diseases which can be prevented by vaccination are considered.

Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development.

Two vaccines focused on the prevention of HPV-related diseases have been introduced in the last decade, the quadrivalent vaccine Gardasil and the bivalent vaccine Cervarix. They are targeted to prevent precancerous and cancerous lesions not only of the cervix, but also of the vulva, vagina, anal and head-neck region. Furthermore, the protection of the quadrivalent vaccine Gardasil includes also genital warts and recurrent respiratory Papillomatosis, two benign conditions with high socio-economic impact. Although their efficacy in reducing the burden of HPV-related pathologies has been already documented, second-generation HPV vaccines are being developed in order to overcome major limitations, above all the cost of production, distribution and acceptance, thus promoting an easier access to vaccination, especially in developing countries. Recently a new multivalent VLP vaccine active against nine HPV subtypes, called Gardasil 9 (Merck & Co., Inc., Whitehouse Station, NJ, USA), has been approved, showing promising preliminary results. In this article, we outline the strategies adopted for second-generation HPV vaccine engineering, the latest HPV vaccines available at this time, as well as those currently in development.

Adolescent vaccine co-administration and coverage in New York City: 2007-2013.

OBJECTIVES: To investigate adolescent vaccination in New York City, we assessed tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate (MCV4), and human papillomavirus (HPV) vaccine uptake, vaccine co-administration, and catch-up coverage over time. METHODS: We analyzed data from the Citywide Immunization Registry, a population-based immunization information system, to measure vaccine uptake and co-administration, defined as a Tdap vaccination visit where MCV4 or HPV vaccine was co-administered, among 11-year-olds. Catch-up vaccinations were evaluated through 2013 for adolescents born 1996 to 2000, by birth cohort. HPV vaccination among boys included data from 2010 to 2013. RESULTS: Adolescent vaccine administration was greatest during the back-to-school months of August to October and was highest for Tdap. Although MCV4 uptake improved over the study years, HPV vaccine uptake among girls stagnated; boys achieved similar uptake of HPV vaccine by 2012. By 2013, 65.4% had MCV4 co-administered with Tdap vaccine, whereas 28.4% of girls and 25.9% of boys had their first dose of HPV vaccine co-administered. By age 17, Tdap and MCV4 vaccination coverage increased to 97.5% and 92.8%, respectively, whereas ≥1-dose and 3-dose HPV vaccination coverage were, respectively, 77.5% and 53.1% for girls and 49.3% and 21.6% for boys. Age-specific vaccination coverage increased with each successive birth cohort (P < .001). CONCLUSIONS: From 2007 to 2013, there were greater improvements in Tdap and MCV4 vaccination than HPV vaccination, for which co-administration with Tdap vaccine and coverage through adolescence remained lower. Parent and provider outreach efforts should promote timely HPV vaccination for all adolescents and vaccine co-administration.

The contribution of vaccination to global health: past, present and future.

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

Monitoring what governments "give for" and "spend on" vaccine procurement: Vaccine Procurement Assistance and Vaccine Procurement Baseline.

BACKGROUND: The Global Vaccine Action Plan will require, inter alia, the mobilization of financial resources from donors and national governments - both rich and poor. Vaccine Procurement Assistance (VPA) and Vaccine Procurement Baseline (VPB) are two metrics that could measure government performance and track resources in this arena. VPA is proposed as a new subcategory of Official Development Assistance (ODA) given for the procurement of vaccines and VPB is a previously suggested measure of the share of Gross Domestic Product (GDP) that governments spend on their own vaccine procurement. OBJECTIVE: To determine realistic targets for VPA and VPB. METHODS: Organization for Economic Co-Operation and Development (OECD) and World Bank data for 2009 were analyzed to determine the proportions of bilateral ODA from the 23 Development Assistance Committee (DAC) countries disbursed (as % of GDP in current US$) for infectious disease control. DAC country contributions to the GAVI Alliance for 2009 were assessed as a measure of multilateral donor support for vaccines and immunization programs. FINDINGS: In 2009, total DAC bilateral ODA was 0.16% of global GDP and 0.25% of DAC GDP. As a percentage of GDP, Norway (0.013%) and United Kingdom (0.0085%) disbursed the greatest proportion of bilateral ODA for infectious disease control, and Norway (0.024%) and Canada (0.008%) made the greatest contributions to the GAVI Alliance. In 2009 0.02% of DAC GDP was US$7.61 billion and 0.02% of the GDP of the poorest 117 countries was US$2.88 billion. CONCLUSIONS: Adopting 0.02% GDP as minimum targets for both VPA and VPB is based on realistic estimates of what both developed and developing countries should spend, and can afford to spend, to jointly ensure procurement of vaccines recommended by national and global bodies. New OECD purpose codes are needed to specifically track ODA disbursed for a) vaccine procurement; and b) immunization programs.