DNA methylation as a triage tool for cervical cancer screening - A meeting report.

Introduction: DNA methylation is proposed as a novel biomarker able to monitor molecular events in human papillomavirus (HPV) infection pathophysiology, enabling the distinction between HPV-induced lesions with regression potential from those that may progress to HPV-related cancer. Methods: This meeting report summarises the presentations and expert discussions during the HPV Prevention and Control Board-focused topic technical meeting on DNA methylation validation in clinician-collected and self-collected samples, novel DNA methylation markers discovery, implementation in cervical cancer screening programs, and their potential in women living with human immunodeficiency virus (HIV). Results: Data presented in the meeting showed that HPV-positive, baseline methylation-negative women have a lower cumulative cervical cancer incidence than baseline cytology-negative women, making DNA methylation an attractive triage strategy. However, additional standardised data in different settings (low- versus high-income settings), samples (clinician-collected and self-collected), study designs (prospective, modelling, impact) and populations (immunocompetent women, women living with HIV) are needed. Conclusion: Establishing international validation guidelines were identified as the way forward towards accurate validation and subsequent implementation in current screening programs.

Global perspectives of determinants influencing HPV vaccine introduction and scale-up in low- and middle-income countries.

Achieving WHO cervical cancer elimination goals will necessitate efforts to increase HPV vaccine access and coverage in low-and-middle-income countries (LMICs). Although LMICs account for the majority of cervical cancer cases globally, scale-up of HPV vaccine programs and progress toward coverage targets in LMICs has been largely insufficient. Understanding the barriers and facilitators that stakeholders face in the introduction and scale-up of HPV vaccination programs will be pivotal in ensuring that LMICs are equipped to optimize the implementation of HPV vaccination programs. This qualitative study interviewed 13 global stakeholders categorized as either academic partners or global immunization partners to ascertain perspectives regarding factors affecting the introduction and scale-up of HPV vaccination programs in LMICs. Global stakeholders were selected as their perspectives have not been as readily highlighted within the literature despite their key role in HPV vaccination programming. The results of this investigation identified upstream (e.g., financial considerations, vaccine prioritization, global supply, capacity and delivery, and vaccine accessibility, equity, and ethics) and downstream (e.g., vaccine acceptability and hesitancy, communications, advocacy, and social mobilization) determinants that impact program introduction and scale-up and confirmed that strong political commitment and governance are significant in garnering support for HPV vaccines. As LMICs introduce HPV vaccines into their national immunization programs and develop plans for scaling up vaccination efforts, strategic approaches to communications and advocacy will also be needed to successfully meet coverage targets.

An update on one-dose HPV vaccine studies, immunobridging and humoral immune responses - A meeting report.

The 12th HPV Prevention and Control meeting was held on June 2-3, 2022, in Antwerp, Belgium. This technical meeting focused on several topics. This report summarises the discussions and lessons learned on two topics: an update on one-dose HPV vaccination studies and humoral immune responses upon HPV vaccination. Long-term follow-up studies from Costa Rica (eleven years) and India (ten years) report stable levels of antibodies after a single HPV vaccination. High vaccine effectiveness against incident persistent HPV 16/18 infection was seen in India (95.4%, 85.0-99.9) ten years postvaccination and in Kenya (97.5%, 81.7-99.7) eighteen months postvaccination, an important observation in a setting with a higher HPV prevalence. The potential impact of HPV vaccination using a one-dose schedule in India was modelled and showed that implementation of one-dose schedule can contribute towards achieving WHO Cervical Cancer elimination goals. These data support the WHO SAGE recommendations for adopting a one-dose schedule for females aged 9-20 years. Immunobridging studies were discussed during the meeting. General agreement was reached that when thoughtfully applied, they can support and accelerate the expanded use of HPV vaccine with new vaccine schedules, age cohorts, or vaccine formulations. Internationally standardised measurements of HPV immune responses important for the progress of HPV vaccinology field. Humoral immune responses upon HPV vaccination plateau at 24 months regardless of number of doses, therefore, data should be analysed after at least 24 months of follow-up to bridge studies accurately.

Prevention and control of HPV and HPV-related cancers in France: the evolving landscape and the way forward - a meeting report.

Misinformation regarding HPV vaccine safety and benefits has resulted in low coverage within the eligible French population. HPV vaccination is safe and efficacious in preventing HPV infections in adolescents. However, reaching optimal coverage in countries such as France is challenging due to misinformation, among other factors. Moreover, disparities exist in cervical cancer screening programs. To support the government health promotion policy aimed at improving prevention and control of HPV-related cancers in France, the Human Papillomavirus Prevention and Control Board (HPV-PCB), in collaboration with local experts, held a meeting in Annecy, France (December 2021).HPV-PCB is an independent, multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV control programs.After a one-and-a-half-day meeting, participants concluded that multi-pronged strategies are required to expand vaccination coverage and screening. Vaccine acceptance could be improved by: 1) strenghtening existing trust in clinicians by continuous training of current and upcoming/pre-service healthcare professionals (HCPs), 2) improving health literacy among adolescents and the public through school and social media platforms, and 3) providing full reimbursement of the gender-neutral HPV vaccine, as a strong signal that this vaccination is essential.The discussions on HPV infections control focused on the need to: 1) encourage HCPs to facilitate patient data collection to support performance assessment of the national cervical cancer screening program, 2) advance the transition from cytology to HPV-based screening, 3) improve cancer prevention training and awareness for all HCPs involved in screening, including midwives, 4) identifying patient barriers to invitation acceptance, and 5) promoting urine or vaginal self-sampling screening techniques to improve acceptability, while establishing appropriate follow-up strategies for HPV-positive women. This report covers some critical findings, key challenges, and future steps to improve the status of HPV prevention and control measures in the country.

Planning, implementation, and sustaining high coverage of human papillomavirus (HPV) vaccination programs: What works in the context of low-resource countries?

Cervical cancer due to human papillomavirus (HPV) infection is a leading cause of mortality among women in low-resource settings. Many Sub-Saharan African countries have introduced HPV vaccination programs at the national level in the last few years. However, countries are struggling to maintain sustainable coverage. This study focuses on the introduction and sustainability challenges, context-specific key lessons learned, and mechanisms of action to achieve high sustainable coverage from low and lower-middle-income countries (LLMICs) that have introduced HPV vaccination programs by collating evidence from a literature review and key informant interviews. Local data availability was a challenge across countries, with the lack or absence of registries, data collection and reporting mechanisms. Multi-sectoral coordination and early involvement of key stakeholders were cited as an integral part of HPV programs and facilitators for sustainable coverage. Key informants identified periodic sensitization and training as critical due to high staff turnover. Health workforce mobilization was fundamental to ensure that the health workforce is aware of the disease etiology, eligibility requirements, and can dispel misinformation. Schools were reported to be an ideal sustainable platform for vaccination. However, this required teachers to be trained, which was often not considered in the programs. District-level staff were often poorly informed and lacked the technical and logistic capacity to support vaccination rounds and data collection. To improve the sustainability of HPV vaccination programs, there is a need for timely microplanning, efficient preparedness assessment, assessing training approaches, periodic training, finding innovative ways to achieve equity and adoption of a bottom-up approach to ensure that processes between districts and central level are well-connected and resources are distributed efficiently.

Factors influencing the prioritization of vaccines by policymakers in low- and middle-income countries: a scoping review.

Vaccination decision making in low- and middle-income countries (LMICs) has become increasingly complex, particularly in the context of numerous competing health challenges. LMICs have to make difficult choices on which vaccines to prioritize for introduction while considering a wide range of factors such as disease burden, vaccine impact, vaccine characteristics, financing and health care infrastructures, whilst adapting to each country's specific contexts. Our scoping review reviewed the factors that influence decision-making among policymakers for the introduction of new vaccines in LMICs. We identified the specific data points that are factored into the decision-making process for new vaccine introduction, whilst also documenting whether there have been any changes in decision-making criteria in new vaccine introduction over the last two decades. A comprehensive database search was conducted using a search strategy consisting of key terms and Medical Subject Headings (MeSH) phrases related to policy, decision-making, vaccine introduction, immunization programmes and LMICs. Articles were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 843 articles were identified, with 34 articles retained after abstract screening, full-text screening and grading with the mixed methods appraisal tool (MMAT). The Burchett framework for new vaccine introduction was used to identify indicators for vaccine-decision making and guided data extraction. Articles in our study represented a diverse range of perspectives and methodologies. Across articles, the importance of the disease, which included disease burden, costs of disease and political prioritization, coupled with economic factors related to vaccine price, affordability and financing were the most common criteria considered for new vaccine introduction. Our review identified two additional criteria in the decision-making process for vaccine introduction that were not included in the Burchett framework: communication and sociocultural considerations. Data from this review can support informed decision-making for vaccine introduction amongst policymakers and stakeholders in LMICs.

Key decision-making factors for human papillomavirus (HPV) vaccine program introduction in low-and-middle-income-countries: Global and national stakeholder perspectives.

Low-and-middle-income countries (LMICs) experience a high burden of cervical cancer. The human papillomavirus (HPV) vaccine prevents high-risk strains of HPV that cause cervical cancer; however, the integration of HPV vaccines into national immunization programs within many LMICs has been suboptimal. Our study evaluated key factors that drive the decision-making process for the implementation of HPV vaccine programs in LMICs. Stakeholder analysis and semi-structured in-depth interviews were conducted with national and global stakeholders. Interview data were analyzed through qualitative descriptive methods. Findings from our study revealed the decision-making process for HPV vaccines requires the involvement of multiple institutions and stakeholders from national and global levels, with decision-making being a country-specific process. Partner considerations, locally driven processes, availability of data, and infrastructure and resource considerations were found to be critical factors in the decision-making process. Future programs should evaluate the best approaches for investing in initiatives to enhance coordination, ensure vaccine introduction is locally driven, increase the availability of data needed for decision-making, and equip countries with the necessary resources to guide country decision-making in the face of increasingly complex decision-making environments.

Which interventions improve HPV vaccination uptake and intention in children, adolescents and young adults? An umbrella review.

BACKGROUND: Human papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are. METHODS: We conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail. MAIN RESULTS: From 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents. CONCLUSION: The evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

HPV prevention and control - The way forward.

The global confrontation with COVID-19 has not only diverted current healthcare resources to deal with the infection but has also resulted in increased resources in the areas of testing and screening, as well as educating most of the global public of the benefits of vaccination. When the COVID-19 pandemic eventually recedes, the opportunity must not be missed to ensure that these newly created resources are maintained and redeployed for use in testing and immunisation against other vaccine-preventable infectious diseases. A notable example is infection by human papillomavirus (HPV), the commonest sexually transmitted human virus and the leading cause of a variety of cancers in both men and women, such as cervical, head and neck, anal, vaginal, vulvar and penile cancers. The most important is cervical cancer, the objective of the global elimination goals targeting the vaccination of young female and male adolescents, screening all women and treatment of all infected women. As the campaigns to control SARS-CoV-2, the eradication of HPV-induced cancers also relies on effective prevention and control programs. The lessons learned and the technical, logistical and human resources which have been established to combat COVID-19 by vaccination and testing must be applied to the eradication of other infections which affect the global population. This commentary summarizes the opportunities that the COVID-19 pandemic has created for HPV prevention and control, lists the already available tools for HPV control, and emphasizes the potential public health threats amidst the ongoing COVID-19 pandemic.

Human papillomavirus vaccination in adults: impact, opportunities and challenges - a meeting report.

For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9-15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women.

Impact of the COVID-19 pandemic on human papillomavirus-based testing services to support cervical cancer screening.

INTRODUCTION: The World Health Organization elimination goal for cervical cancer relies on screening 70% of women at ages 35 and 45, preferentially through molecular HPV testing. The SARS-CoV-2 pandemic has led to an unprecedented demand for molecular tests and platforms. Our objective was to gain insight into the impact of SARS-CoV-2 on the actual or anticipated shortage of tests, equipment, consumables, and staff required to deliver molecular HPV laboratory services and to consider the implications for the sustainability and development of cervical screening programs. METHODS: A 19-item online questionnaire was created and made available online between December 2020 and February 2021. Five companies with clinically validated HPV and SARS-CoV-2 tests in their portfolios were invited to provide a statement on the volumes of molecular COVID-19 tests produced, relevant changes to manufacturing capacity, and their current and post-pandemic strategy for HPV tests. RESULTS: We received responses from 57 laboratories representing 30 countries and six continents. Among these, 74% reported experiencing a supply shortage, 54% reported a shortage of personnel, and 33% reported delays in ordering equipment. Three companies described expansion of manufacturing lines, investment in diagnostic infrastructure, and scale-up of manufacturing capacity. Two companies specifically referred to opportunities for the use of platforms for COVID-19 testing to support HPV testing in time. CONCLUSIONS: The demand for SARS-CoV-2 testing is competing with HPV testing, compounded by a shortage of staff. This represents a challenge for existing laboratory services and for settings keen to implement HPV-based screening. However, supply challenges may be addressed in time, given the significant investment in manufacturing capacity. In addition, innovation around molecular COVID-19 testing systems may result in solutions that address the shortage of rapid low-cost HPV testing systems for low-resource settings. Finally, because the demand for COVID-19 testing is likely to decrease, this may release both workforce and platform capacity for high-throughput HPV testing. The global health community should be alert to the opportunities around innovation and capacity if cervical cancer elimination goals are to be reached.

Prevention and control of HPV infection and HPV-related cancers in Colombia- a meeting report.

The Human Papillomavirus (HPV) Prevention and Control Board is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV control programs. In response to drastic drop of vaccine coverage following the adverse event crisis in Carmen del Bolivar, Colombia, the HPV Prevention and Control Board in collaboration with the Colombian National Cancer Institute and Colombian League Against Cancer convened a meeting in Bogota, Columbia (November 2018). The goal of the meeting was to bring together national and international group of experts to report the disease burden, epidemiology and surveillance of HPV and HPV-related cancers, to discuss the successes and especially the challenges of HPV vaccination and screening in Colombia, as well as the lessons learnt from neighbouring countries. The meeting provided a platform to confer various stakeholder's perspectives, including the role of the Colombian healthcare system and to catalyse various parts of the public health community in Colombia into effective action. The conclusion of the meeting included following suggestions to strengthen HPV prevention and control: 1) Re-introducing school-based vaccine programs, 2) Integrating primary and secondary prevention programs, 3) Developing an innovative crisis communication plan targeting healthcare workers, teachers and general population, 4) Building trust through efficient and timely communication, 5) Building strong relationship with media to ensure a stable vaccination campaign support, and 6) Promoting empathy among healthcare professionals towards patients to build trust and communicate effectively.