Vaccine

National introduction of human papillomavirus (HPV) vaccine in Tanzania: Programmatic decision-making and implementation

Cervical cancer is the leading cause of cancer among women in Tanzania, with approximately 10,000 new cases and 7,000 deaths annually. In April 2018, the Government of Tanzania introduced 2 doses of human papillomavirus (HPV) vaccine nationally to adolescent girls to prevent cervical cancer, following a successful 2-year pilot introduction of the vaccine in the Kilimanjaro Region. We interviewed key informants at the national level in Tanzania from February to November 2019, using a semi-structured tool to better understand national decision-making and program implementation. We conducted a comprehensive desk review of HPV vaccine introduction materials and reviewed administrative coverage data. Ten key informants were interviewed from the Ministry of Health, Community Development, Gender, Elderly, and Children, the World Health Organization, and other partners, and HPV vaccine planning documents and administrative coverage data were reviewed during the desk review. Tanzania introduced HPV vaccine to a single-age cohort of 14-year-old girls, with the decision-making process involving the Tanzania Immunization Technical Advisory Group and the national Interagency Coordination Committee. HPV vaccine was integrated into the routine immunization delivery strategy, available at health facilities and through outreach services at community sites, community mobile sites (>10 km from the health facility), and primary and secondary schools. Pre-introduction activities included trainings and microplanning workshops for health workers and school personnel at the national, regional, council, and health facility levels. Over 6,000 health workers and 22,000 school personnel were trained nationwide. Stakeholder and primary health care committee meetings were also conducted at the national level and in each of the regions as part of the advocacy and communication strategy. Administrative coverage of the first dose of HPV vaccine at the end of 2019 was 78%, and second dose coverage was 49%. No adverse events following HPV vaccination were reported to the national level. Tanzania successfully introduced HPV vaccine nationally targeting 14-year-old girls, using routine delivery strategies. Continued monitoring of vaccination coverage will be important to ensure full 2-dose vaccination of eligible girls. Tanzania can consider periodic intensified vaccination and targeted social mobilization efforts, as needed.

HPV vaccine acceptance in West Africa: A systematic literature review

Human papillomavirus (HPV) infections are mostly sexually transmitted and cause the greatest share of infection-associated cancers. Each year more than half a million women are diagnosed with cervical cancer and the mortality rate in West Africa is over ten times higher than that of Northern Europe. HPV vaccines are highly effective at preventing various strains of the infection. However, vaccine hesitancy and access issues have led to low HPV vaccine acceptance in certain countries. A search strategy was developed in PubMed and included an extensive list of keywords and related MeSH/subject headings to capture the many dimensions and expressions of vaccine access, confidence, trust and hesitancy related to HPV vaccination in West Africa. Thirty-five articles were included by full text. Most studies were conducted in Nigeria. Three were conducted in Mali, and one each in Côte d'Ivoire, Ghana and Senegal. The main concerns relating to the vaccine were inadequate information, cost and safety concerns. Several studies also mentioned fertility and promiscuity concerns. Despite over half of West African countries introducing an HPV vaccine pilot project, there is a scarcity of literature on HPV vaccine acceptance in the region. It is important to understand how cultural and gender dynamics in different settings can influence peoples' vaccination decisions. This can be done through in-depth local ethnographies, taking the views of all community members and influencers into account, and complemented by in-depth individual interviews and focus groups.

Head-to-head immunogenicity comparison of one-dose Cecolin and Gardasil in Chinese girls aged 9–14 years: A randomized and open-label clinical trial

The World Health Organization (WHO) urges global administration of at least one dose of the HPV vaccine, particularly for girls aged 9-14, to work towards the elimination of cervical cancer. However, data on the efficacy of a single dose of Cecolin®, a bivalent HPV vaccine, remain quite limited. Therefore, it is crucial to design studies investigating the protective effects of a single dose of Cecolin® in Chinese girls. The randomized clinical trial began on February 23, 2023 (NCT06345885). 198 Chinese girls aged 9-14 received a single dose of Cecolin® or Gardasil®. Seroconversion rates and geometric mean titers (GMTs) for HPV16 and HPV18 were assessed at one and two months post-vaccination. Non-inferiority was declared if the lower limit of the 95 % confidence interval (CI) exceeded -5 %. Safety of vaccine was evaluated in all vaccinated participants. At one month post-vaccination, both the Cecolin® and Gardasil® groups achieved 100 % seroconversion for HPV16 antibodies. The seroconversion rates for HPV18 were 97.9 % (95 % CI: 92.5 %, 99.7 %) in the Cecolin® group and 95.6 % (95 % CI: 89.1 %, 98.8 %) in the Gardasil® group. The GMTs in the Cecolin® group were significantly higher than those in the Gardasil® group for both HPV types, with GMT ratios of 1.5 (1.1, 2.1) for HPV16 and 2.84 (2.0, 4.1) for HPV18. The seroconversion rates and GMT ratios one month after a single dose of Cecolin® were non-inferior to those of Gardasil®, with results remaining consistent at two months. The incidence of adverse events was similar between the two groups throughout the study, with no statistically significant differences. The immunogenicity and safety of a single dose of Cecolin® in Chinese girls aged 9-14 years were comparable to those of Gardasil. These findings support the use of single-dose Cecolin® to enhance HPV vaccination coverage for cervical cancer prevention.

Integrating HPV vaccine service delivery with adolescent health programmes – Experiences and perspectives from selected countries in Africa

Primary prevention of human papillomavirus (HPV) infection is particularly important in Africa, where there is a high and accelerating burden of cervical cancer. Stakeholders have increasingly called for integration of other services with HPV vaccination in low- and middle-income countries, yet successful and sustainable integration requires intensive resource inputs, and few countries in Africa have tested integrated approaches. We describe co-author experience and previously published assessments to present the experiences of four African countries, Senegal, Togo, Tanzania, and Lesotho, with integrating HPV vaccine services with other programmes and services. The resulting case series explores how countries are operationalizing the concept of integration and describes contextual factors for success and sustainability. A simple three-level framework for describing HPV vaccine integrated service delivery has emerged to guide future endeavors.

Prevalence of high-risk human papillomavirus among women with different HPV-vaccination status in Sichuan, China

While HPV vaccination has significantly reduced HPV 16/18 prevalence in other countries, HPV vaccination was not approved in China until 2016, most of those vaccinated are over the age of 20, the efficacy remains unknown. In this cross-sectional study, we analyzed cervical specimens from 6971 women (20-40 years) undergoing routine gynecological check-ups (2022-2024). The Overall HR-HPV prevalence was 11.12% (775/6971). Vaccination reduced HPV 16/18 prevalence by 60.5% (RR = 0.395, 95% CI: 0.280-0.558) with the 2/4-valent vaccine and 59.8% (RR = 0.402, 95% CI: 0.277-0.583) with the 9-valent vaccine. However, non-vaccine-targeted HR-HPV types (35/39/51/56/59/66/68) were more frequent in 9-valent recipients (6.88% vs. 4.49% in unvaccinated women, p < 0.05), offsetting the decline in overall HR-HPV prevalence. CIN2+ incidence was significantly lower in vaccinated (2/4-valent: 1.97%; 9-valent: 1.16%) than unvaccinated women (3.60%, p < 0.05). These results demonstrate that HPV vaccines effectively reduced vaccine-type infections and the incidence of CIN2+ lesions. It is worth to mention that the prevalence of non-vaccine-targeted HPV types has demonstrated a significant increase. These findings provide compelling evidence to inform cervical cancer screening strategies and vaccination programs in China.

Understanding parental HPV vaccination decision in China through the lens of vaccine hesitancy and preference heterogeneity: a discrete choice experiment

Human papillomavirus (HPV) vaccination is an effective strategy for preventing cervical cancer. However, persistent vaccine hesitancy remains a major barrier to widespread HPV vaccination. In line with the WHO's global strategy to eliminate cervical cancer, China announced in September 2025 that HPV vaccination would be included in the National Immunisation Programme. Understanding how parental preferences for different HPV vaccine attributes differ according to level of vaccine hesitancy is therefore essential to inform effective communication strategies and support the successful implementation of the new national programme. We recruited parents of girls aged 9-14 years in mainland China who had not received the HPV vaccine. A total of 1062 participants completed a discrete choice experiment to examine parental preferences for vaccinating their children. Five vaccine attributes were evaluated: protection efficacy, duration of protection, possibility of minor side effects, vaccine's country of manufacture, and price. The HPV Vaccine Hesitancy Scale was used to measure participants' degree of vaccine hesitancy. A mixed logit model was employed to explore preference heterogeneity according to level of vaccine hesitancy among participants. All vaccine attributes significantly influenced parental preferences. Protective efficacy and duration of protection were the most important attributes for both high-hesitancy and low-hesitancy parents. Preferences differed by hesitancy level: parents with higher hesitancy assigned greater weight to efficacy and duration, and showed greater preference for imported vaccines. Under the baseline scenario, the predicted uptake was 35.9%, whereas the optimal scenario, characterised by high efficacy, forever protection, low cost, minimal side effects, and domestic production, was projected to increase uptake to 99.2%. Parental preference of HPV vaccine attributes varied across vaccine hesitancy groups. Optimisation of vaccine attributes, particularly protection efficacy and duration of protection, may substantially enhance acceptance, supported by effective public communication and strengthened trust in domestically produced vaccines. These findings provide evidence to inform targeted strategies for increasing HPV vaccination coverage in China.

The role of HPV single-dose vaccination in expanding access in GAVI-supported countries during a period of supply constraints

Over 2023 and 2024, 19 of the countries that were supported by Gavi to purchase HPV vaccines adopted a single-dose HPV vaccination schedule. The goal of this study is to estimate the impact on vaccination access and the number of cervical cancers averted compared to a two-dose schedule. We estimated the population that could be targeted in countries supported by Gavi to purchase HPV vaccines. We used UNICEF shipment plans to identify the number of HPV doses shipped to each country in 2023 and 2024, plus information supplied by Gavi on the dose schedule implemented in each country and year, adjusting for vaccine wastage. We computed the number of girls that could have been reached, first assuming complete utilization of all shipped doses under a single-dose schedule, and second assuming a counterfactual scenario where all countries would have used a 2-dose schedule. We then compared this to country-reported data on the number of girls actually vaccinated. For each of the three scenarios we modeled the number of cervical cancers averted using HPVsim, a microsimulation model calibrated to each country. We calculate that the introduction of single-dose HPV vaccination in Gavi-supported countries would have allowed these countries to target 23.3M additional girls if all supply was utilized. Reported data on girls vaccinated indicates that in actuality an additional 18.5M girls were reached due to adoption of single-dose. We estimate that the use of single-dose schedule in 2023 and 2024 could have averted up to 370,000 (356,000-376,000) additional future cervical cancers if all supply had been utilized, and 297,000 (222,000-369,000) given actual utilization. The single-dose HPV vaccination strategy has had a substantial positive impact on cervical cancer elimination in context of supply constraints affecting low and middle-income countries.

Prioritization of HPV vaccine preventable diseases among emerging adults – Implications for health education and communication

Emerging adults are at the highest risk for Human papillomavirus (HPV). HPV increases the risk of cervical, oropharyngeal, and anogenital cancers and skin lesions, leading to genital warts. However, many are unaware of the full spectrum of diseases associated with HPV. This study aimed to identify which HPV vaccine-preventable diseases are the highest priority among emerging adults and examine demographic factors related to prioritization, to inform education and communication strategies. Participants were recruited to complete a voluntary, one-time, online survey at two no-cost vaccine clinics in September and October 2024. This study is limited to respondents aged 18 to 25 (n = 454; 61.9% female; 54.8% non-Hispanic white). After being presented with a list of 7 HPV vaccine-preventable diseases, participants were asked to rank them in order of importance. Frequency analysis was conducted on the top-ranked outcome. Prioritization of outcomes, grouped by sex specificity (female, male, non-sex-specific) and latency (genital warts, cancers), was examined in relation to socio-demographic characteristics. Cervical cancer (26.87%), genital warts (19.82%), and oropharyngeal cancer (17.8%) were most often the highest priority. More females than males (68% vs. 3.47%) prioritized female-specific cancers, while more males than females (44.5% vs. 13.5%) prioritized non-sex-specific cancers (χ2 = 219.08; p < 0.001). Odds of prioritizing genital warts over cancers were higher among non-Hispanic Asian (aOR = 2.19; 95% CI = 1.28-3.76) and non-Hispanic other race (aOR = 2.73; 95% CI = 1.32-5.68). HPV vaccine promotion should continue to emphasize all outcomes or be tailored to address the outcome priorities of each group, including males and racial minorities.

Human papillomavirus vaccination coverage and willingness among women in mainland China: A meta-analysis based on the COM-B model

To estimate human papillomavirus (HPV) vaccination coverage and vaccination willingness among women in mainland China and identify the influencing factors using the Capability, Opportunity, and Motivation model of Behavior (COMB). PubMed, Web of Science, Cochrane Library, Embase, and Chinese databases including CNKI, Wanfang Data, VIP, and CBM were searched. Pooled HPV vaccination coverage and willingness were calculated using a random-effects model with 95 % confidence intervals (CIs). Subgroup analyses and meta-regression were performed to explore heterogeneity. The COM-B model and the Theoretical Domains Framework (TDF) were employed to identify factors associated with vaccination coverage and willingness. Dichotomous outcomes were presented as odds ratios (OR) with the corresponding 95 % CIs. A total of 155 articles, including 10,965,863 mainland Chinese women, were included. The pooled vaccination coverage in 80 included studies was 9.5 % (95 % CI: 7.6 %-11.6 %). Subgroup analysis indicated a higher vaccination rate among women undergoing HPV or cervical cancer screening (16.9 %, 95 % CI: 10.5 %-24.4 %) and among healthcare workers (13.4 %, 95 % CI: 5.6 %-23.8 %). Vaccination willingness, based on 126 studies, was 70.6 % (95 % CI: 66.8 %-74.3 %). Furthermore, the three dimensions of the COM-B model were found to significantly influence both vaccination coverage and willingness (P < 0.05), with capability showed the strongest correlation with HPV vaccination coverage (OR = 2.96, 95 % CI: 2.20-3.99). There was a significant gap between vaccination willingness and actual coverage among mainland Chinese women. HPV vaccination status of family members or friends and knowledge of HPV and its vaccines were associated with higher vaccination rates.

Key players and determinants improving human papillomavirus vaccination coverage in Cameroon: a cross-sectional nationwide health workers survey

Human papillomavirus (HPV) is a significant sexually transmissible infection associated with over 90 % of cervical cancers, most of which could be prevented by vaccination. Despite the merit of the HPV vaccine, coverage remained less than 20 % in Cameroon until the onset of single-dose vaccination for adolescent boys and girls in 2023, when the country recorded 57 % and 26 % HPV vaccination coverage for girls and boys, respectively. This study investigated the drivers of caregivers and the key community players that facilitated their work to enhance the uptake of the HPV vaccine in Cameroon. A nationwide cross-sectional survey was conducted from August 2023 to July 2024 using an online questionnaire developed in Kobo Toolbox. Study participants included healthcare personnel from the country's ten regions, districts, and health facilities. SPSS was used in data analysis. The Chi-square test was used to identify differences in vaccination drivers. Multiple logistic regression analyses were performed, and the results were reported with 95 % confidence intervals and a 5 % significance level. In total, 1225 health workers (HW) were sampled. Most participants were aware of the HPV vaccine and willing to promote its uptake (83 %). HW knowledge of HPV was statistically significantly associated with increased HPV vaccination uptake by adolescents (OR = 3.2, 95 %CI: 1.6-6.4, P = 0.01). A strong association was also found between HW working at the vaccination unit and the vaccination of adolescent girls (OR = 2.5, 95 %CI: 1.7-3.5, p < 0.01). The key actors reported by HW to favor vaccination were parents (29 %), traditional authorities (29 %), religious leaders (19 %), and teachers (19 %). Key vaccination sites included community (50 %), schools (29 %), and health facilities (20 %). Investigating the drivers of HPV vaccination in Cameroon in 2023, this research shows the crucial role HW's knowledge of HPV plays in promoting HPV vaccination. Additionally, parents, traditional leaders, and teachers were identified by HW as key players in promoting vaccination.

Factors associated with HPV vaccine hesitancy: A nationally representative cross-sectional study

HPV related tumors continue to be a global leading cause of cancer mainly due to cervical cancer (CC) burden. In Brazil, CC is the third most common cancer and the fourth highest cancer mortality rate among women. HPV vaccine mass immunization represents the current most promising intervention for CC prevention. It was first implemented in the Brazilian public health system in 2014, however, despite a history of excellent coverage for other vaccines, HPV vaccine uptake is below the necessary threshold for CC elimination. Identifying the factors that influence HPV vaccine hesitancy is an essential step to further develop strategies to improve vaccination coverage. The aim of this study is to provide insights into whether or not Brazilians are resistant to HPV vaccination and to determine the factors and variables that influence this decision. This is a population-based cross-sectional study which used quantitative methodology through personal interviews. A total of 2010 interviews were planned to result in error margins of 2 percentage points, more or less considering a 95 % confidence level, encompassing all five Brazilian regions. Cities of different sizes and complexities were included in the sample, as capitals and cities in both metropolitan and rural areas. The research was carried out with the Brazilian population aged 16 and over, interviewees were approached at points of population flow. Between June 12th and 16th 2023, a total of 2010 personal interviews were done, with participants from all five Brazilian regions. The prevalence of vaccine resistance was 5.97 % (95 % confidence interval [CI], 4.93-7.23) among those interviewed. A multivariate analysis demonstrated greater resistance to the vaccine among men (prevalence ratios (PR): 1.58; 95 %CI 1.06-2.34; p: 0.023) and residents in the South region of the country (PR: 1.77; 95 %CI, 1.06-2.94; p: 0.028). The three main reasons for refusing the vaccine reported by the participants were: lack of knowledge about the HPV vaccine; difficulty in accessing the vaccine; and lack of vaccine prescription by health professionals. Safety was the main reason not to vaccinate, cited by 10 %. Despite HPV vaccine availability in Brazil at the public health system, vaccination coverage remains below the target for both genders. However, according to this analysis, there is a low rate of HPV vaccination hesitancy in the country, being lack of knowledge, difficulty in accessing the vaccine and lack of vaccine prescription by health professionals the main obstacles to adequate adherence. The COVID-19 pandemic doesn't seem to have affected HPV vaccination resistance in the country. Proper strategies for vaccine implementation, including school-based programs, patient-provider communication and education, and integrated monitoring and evaluation strategies are needed, otherwise HPV vaccine programs run the risk of repeating the problems associated with Pap programs in Low- and Middle-Income Countries (LMICs): an efficient, life-saving tool underutilized for cancer prevention.

“If I know about it of course I would give my son and daughter”, barriers to and enablers of accessing human papillomavirus vaccination among women from refugee and asylum-seeking backgrounds resettling in Melbourne, Australia – A qualitative study

Women from refugee and asylum-seeking backgrounds have lower human papillomavirus vaccination (HPVV) rates than host country populations. Improving HPVV rates is important in the prevention of cervical cancer. This qualitative study gained an in-depth understanding of refugee and asylum-seeking women's barriers to and enablers of accessing HPVV services and information for their children post-resettlement in Melbourne, Australia. A qualitative study using semi-structured interviews was conducted with a purposive sample of women from Myanmar, Iraq, Syria and women seeking asylum from different countries. A bi-cultural worker assisted in recruitment and interpreting during data collection. Between December 2021 and September 2023 interviews were conducted in the participants first language with a bi-cultural worker or volunteer interpreting into English during the interview. Audio recordings of English dialogue were transcribed verbatim. Reflexive thematic analysis was used to analyse and report data. Thirty-one refugees and 12 women seeking asylum from eleven countries were interviewed. Barriers to and enablers of HPVV were identified. 1) Barriers to awareness and knowledge of HPVV included: limited awareness of HPVV, lack of access to HPV vaccine information in the pre-arrival context, uncertainty about HPV vaccine safety and effectiveness, gender association with HPVV, negative influence of COVID vaccination on HPV vaccine perceptions. Enablers included: Understanding future benefits: prevention is better than cure 2) Barriers to sociocultural influences included: necessity for HPVV at recommended age, Enablers included: promoting peer support 3) Barriers to health information seeking included: missed opportunities for information delivery at schools and language classes, inconsistent messaging. Enablers included: trust in the education programs, health care provider recommendation, desire for new knowledge. Improving HPVV access requires a multi-faceted approach to enhance women's awareness and knowledge. Key strategies include providing routine HPVV education through resettlement services and school programs, supporting healthcare providers in educating women unfamiliar with HPVV, and delivering clear messaging about the recommended age and addressing gender-related misconceptions.

Exploration of individual socioeconomic and health-related characteristics associated with human papillomavirus vaccination initiation and vaccination series completion among adult females: A comprehensive systematic evidence review with meta-analysis

Human papillomavirus (HPV) vaccination rates among females are lower than the World Health Organization target and vaccination rates specifically among adult females are even much lower. We systematically evaluated individual socioeconomic and health-related characteristics associated with HPV vaccination initiation and vaccination series completion among adult females (PROSPERO: CRD42023445721). We performed a literature search on December 14, 2022, and supplemented the search on August 1, 2023. We pooled appropriate multivariable-adjusted results using an inverse variance random-effects model and expressed the results as odds ratios with associated 95 % confidence intervals. A point pooled significantly increased/decreased odds of 30-69 % was regarded to be strongly associated, and ≥ 70 % was very strongly associated. We included 63 cross-sectional studies. There were strongly increased odds of vaccination initiation among White women compared with Black or Asian women, and those with higher education, health insurance, a history of sexually transmitted infection (STI), receipt of influenza vaccination in the preceding year, not married/cohabiting, not smoking, using contraception, and having visited a healthcare provider in the preceding year. We observed very strongly increased odds of vaccination initiation among those younger and having been born in the country of study. Similarly, there were strongly increased odds of completing the vaccination series for the same variables as initiating vaccination, except for higher education, prior STI, smoking and contraception use. Additional variables associated with strongly increased odds of vaccination series completion not seen in initiation were higher annual household income, being lesbian/bisexual, and having a primary care physician. We observed very strongly increased odds of vaccination series completion similar to vaccination initiation but including for White compared with Black women, higher education, and prior cervical cancer screening. These individual characteristics may be the key to identifying women at increased risk of not being vaccinated against HPV and could inform targeted messaging to drive HPV vaccination.

Cancer fatalism is associated with HPV vaccine uptake among Hispanic emerging adult women in the US

Despite the availability of the Human Papillomavirus (HPV) vaccine, only a small percentage of Hispanic emergent adults in the United States have actually had the vaccination. Due to cancer fatalism, some Hispanic emerging adults may perceive fewer benefits from the HPV vaccine, regardless of its positive health effects. The aim of this study was to determine the relationship between cancer fatalism, knowledge of HPV-associated cancers, and HPV vaccination among Hispanic emerging adult women. Between August and December of 2020, a cross-sectional study was conducted among Hispanic college women aged 18 to 26. A complete case study was conducted with 689 participants. Using an adjusted logistic regression model, the potential factors associated with HPV vaccine uptake were identified. The current research was approved by the Institutional Review Boards of the participating universities. Only 55.6 % of the study population had received at least one dose of the HPV vaccine. The study found that HPV vaccine uptake was positively associated with HPV associated cancer knowledge (aOR = 1.32; 95 % CI = 1.18, 1.47) and was inversely associated with cancer fatalism (aOR = 0.97; 95 % CI = 0.94, 1.00). According to the results of our study, the HPV vaccination rate among Hispanic emerging adult women is low, and it is necessary to identify the factors that influence vaccination rates. There is a critical, unmet need for innovative approaches to improve HPV vaccination in this population and mitigate the incidence of HPV-related cancers. Multiple intervention strategies are required to increase vaccination rates among this population. This study suggests implementing culturally tailored health promotion initiatives that reduce fatalistic beliefs among this population. Furthermore, developing a culturally tailored, age-specific HPV vaccine education and promotion program to increase HPV-associated cancer knowledge among Hispanic emerging adults.

IPVS STATEMENT on HPV vaccination: No longer supply constraints: Towards achieving WHO vaccine targets

The global supply of human papillomavirus (HPV) prophylactic vaccines has been constrained since 2020.Vaccine manufacturers have increased capacity and new HPV vaccines are now available. Vaccine supply is now able to meet the full HPV vaccine demand which has been achieved earlier than predicted.

Assessing real world vaccine effectiveness: A review of Scotland's approach to monitoring human papillomavirus (HPV) vaccine impact on HPV infection and cervical disease

High-risk human papillomavirus (HPV) infections can progress to cervical cancer which is the fourth most common cancer in women globally. In Scotland, the incidence of cervical cancer has a strong socioeconomic deprivation gradient disproportionately affecting women from more deprived areas. An HPV vaccination programme was initiated in Scotland in 2008 targeting girls aged 12-13 years with a catch-up campaign running for the first three years for girls aged up to 18 years. The programme has evolved over the last 16 years with changes in the type of vaccine, dosing schedules and the extension of the programme to boys and gay, bisexual and other men who have sex with men. Vaccine uptake in Scotland has historically been high but has gradually decreased over time and disparities exist in women from more deprived areas of Scotland. The ability to link national immunisation and screening databases in Scotland has allowed direct monitoring of the impact of the HPV vaccine on virological and histological outcomes. Analyses of this linked data have demonstrated real-world evidence of high vaccine effectiveness against HPV infection, cervical disease, and cervical cancer with evidence of herd immunity in unvaccinated women. Continued monitoring is crucial to assess the duration of protection, the impact of vaccine and dosing schedules changes and the emergence of potential type replacement. With the World Health Organisation's aim to eliminate cervical cancer as a public health problem by the next century addressing the inequalities in cervical cancer incidence will be crucial. This will require targeted interventions for women most at risk of cervical cancer to ensure elimination is achieved timely for all women in Scotland.

HPV Vaccine Issues in Japan: A review of our attempts to promote the HPV vaccine and to provide effective evaluation of the problem through social-medical and behavioral-economic perspectives

In Japan, subsidies from local and national government programs for HPV vaccination of girls aged 13-16 began in 2010. By 2013, HPV vaccines were being used routinely for vaccinating girls aged 12-16 as part of its national immunization program. However, in June of 2013, in response to reports of possible adverse reactions to the vaccine, Japan's Ministry of Health, Labor, and Welfare (MHLW) announced a 'temporary suspension' of its governmental recommendation for HPV vaccination. The vaccination rate quickly dropped from 70 % of age-eligible girls to almost zero. It was not until 2021 that the government's recommendation suspension finally ended. The efficacy and safety of the HPV vaccine is now well documented, yet Japan has failed to reestablish any credible level of HPV vaccination. The World Health Organization (WHO) warned that Japan's HPV vaccination debacle was likely to result in real harm to the girls who lacked its protection; something we have already demonstrated with real-world data. To reinvigorate the HPV vaccination program in Japan to its prior levels, in the face of the current high level of HPV vaccine hesitancy, we will have to address the irrationality of human decision-making pointed out by behavioral economics. The Japanese government must act expeditiously to promote stronger cervical cancer control measures.

Longitudinal assessment of nonavalent vaccine HPV types in a sample of sexually active African American women from ten U.S. Cities

Chronic infection with high-risk human papillomavirus is a necessary cause for cervical carcinogenesis. This study examined prevalence of nonavalent vaccine preventable HPV types over four months among sexually active women in the United States. This sub-study obtained meta-data for 80 of the 1,365 women (18-25 years), enrolled in the BRAVO study, a randomized, open-label trial of home screening and treatment of asymptomatic bacterial vaginosis at high-risk for sexually transmitted infections conducted between 2008 and 2013. Participants were randomized to treatment or standard-of-care, and followed every 2-months for 12 months. Stored vaginal swabs from the first three visits were tested for the nine vaccine preventable HPV types using quantitative PCR. Prevalence and associated 95% confidence intervals for the HPV types were assessed using R (version 3.6.1). The average age of the participants was 21.5 (SD ± 2.11) years, with 60% having ever been pregnant and all were African-American. Majority (71%) reported ≥ two sex partners in the prior year with 89% having unprotected vaginal sex and 45% having a new sex partner in the prior year. About 30% had ≥ one of the nine nonavalent vaccine HPV types at all three time points over a period of four months, 15% at two of any three visits, 19% at one of the three visits and 36% were negative for all nine vaccine HPV types at all time points. The most frequently detected HPV vaccine types were 52, 58, 16, and 18. The prevalence of any vaccine HPV types, and high-risk HPV types was 63.8% and 58.8%, respectively. Our findings suggest that HPV vaccination which is currently recommended for all unvaccinated persons through age 26 years, is likely to be more beneficial than previously thought as nonavalent HPV vaccine was not available during the time these data were collected.

Systematic literature review of cross-protective effect of HPV vaccines based on data from randomized clinical trials and real-world evidence

The extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies. PubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts. Data from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3-66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines. RCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.

HPV vaccination: Intention to participate among female senior high school students in Ghana

Cervical cancer is the second most common cancer and the second leading cause of cancer death among women in Ghana. HPV vaccination is expected to be added to the national vaccination schedule in 2023. This study aimed to: i) describe intentions to participate in HPV vaccination and ii) explore factors associated with vaccination intentions among female senior high school students in Ghana. Female students (aged 16-24) were recruited from 17 senior high schools in Ashanti Region. A cross-sectional anonymous self-report paper-and-pen survey assessed students' HPV vaccination intentions using three items, and a range of correlates (individual, parent/family, social networks, service provision). Descriptive statistics were calculated for vaccination intentions, and correlates of intention scores (where higher scores indicate stronger intentions) were explored with a linear mixed-effect model. Of 2400 participants, 64% (95%CI: 62%, 67%) agreed with at least one vaccination intention item. Uncertainty and disagreement with at least one item were endorsed by 51% (95%CI: 49%, 53%) and 44% (95%CI: 42%, 46%) of students, respectively. One-quarter of the students (25%, 95%CI: 23%, 26%) agreed, 12% (95% 11%, 13%) disagreed, and 11% (95%CI: 10%,13%) indicated uncertainty, on all three vaccination intention items. Vaccination uptake was 4.5%. Students were likely to have higher vaccination intention scores if: they had stronger beliefs about vaccine effectiveness; vaccination was recommended by parents, religious leaders and service providers, and vaccinated peers; and it was free. Students were likely to have lower vaccination intention scores if they perceived barriers to vaccination (e.g., side effects). While two-thirds of students had some intention to participate in HPV vaccination, vaccine hesitancy (i.e., uncertainty or disagreement) was apparent. Alongside the rollout of a free national vaccination programme, messaging about vaccination benefits and effectiveness targeting students, as well as parents, religious leaders, service providers and peers would be beneficial given their influential role in students' vaccination intentions.

A novel multi-epitope vaccine of HPV16 E5E6E7 oncoprotein delivered by HBc VLPs induced efficient prophylactic and therapeutic antitumor immunity in tumor mice model

Human papilloma virus type 16 (HPV16) is the most prevalent etiologic agent associated with cervical cancer, and its early proteins E5, E6 and E7 play important roles in cervical epithelium transformation to cervical intraepithelial neoplasia and even cervical cancer. Hence, these oncoproteins are ideal target antigens for developing immunotherapeutic vaccines against HPV-associated infection and cervical cancer. Currently, multi-epitope vaccines have been a promising strategy for immunotherapy for viral infection or cancers. In this study, the E5aa28-46, E6aa37-57 and E7aa26-57 peptides were selected and linked to form a novel multi-epitopes vaccine (E765m), which was inserted into the major immune dominant region (MIR) of hepatitis B virus core antigen (HBc) to construct a HBc-E765m chimeric virus-like particles (cVLPs). The immunogenicity and immunotherapeutic effect of the cVLPs vaccine was evaluated in immunized mice and a tumor-bearing mouse model. The results showed that HBc-E765m cVLPs elicited high E5-, E6- and E7- specific CTL and serum IgG antibody responses, and also relatively high levels of the cytokines IFN-γ, IL-4 and IL-5. More importantly, the cVLPs vaccine significant suppressed tumor growth in mice bearing E5-TC-1 tumors. Our findings provide strong evidence that this novel HBc-E765m cVLPs vaccine could be a candidate vaccine for specific immunotherapy in HPV16-associated cervical intraepithelial neoplasia or cervical cancer.

Knowledge and attitude of students studying at health department towards HPV and HPV vaccination

The human papillomavirus (HPV) is the most common diagnosed sexually transmitted infection in the world. The most frequent disease linked to HPV is cervical cancer as well as other cancers including those of the vulva, vagina, penis, anus, and oropharynx. Our research sought to evaluate the knowledge and attitudes concerning human papillomaviruses and their vaccine among students enrolled in Altınbaş University's faculties of health sciences. A cross-sectional study was carried out using a survey containing 41 questions about demographic variables, knowledge, and attitudes toward HPV and HPV vaccines. The questions were distributed to students via Google form using social media applications such as WhatsApp. The study involved 144 students, 71.5 % of whom were female. 37.5 % of the participants learned about HPV from social media. Knowledge of HPV is present in 82 % of females and 25 % of males. Most of the questions had more accurate replies from female than from male students p < 0.05. As a result, 88 %, 46 %of female respondents and 27 %, 14 %of male respondents, respectively, correctly answered the questions about who should receive HPV vaccinations p < 0.001 and how many doses are necessary. Participants' awareness of HPV, HPV vaccination, and cervical cancer was rather high when compared to other research. However, there are knowledge gaps that need to be corrected and provided through educational programs.

Recent economic evaluation of 1-dose HPV vaccination uses unsupported assumptions

Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9–18 years: A time-varying cohort study

Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain. In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis. Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1 We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1

Using observational data to explore the hypothesis that a single dose of current HPV vaccines can provide durable protection

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis

Cervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region. We systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country. We found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years). Most studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.

Identifying key challenges and optimizing approaches for training of health care professionals for HPV vaccination programmes

Healthcare professionals (HCPs) play a crucial role in building vaccine confidence and promoting vaccination programmes. HCP vaccination recommendations are often the strongest predictor of vaccine uptake, influencing individuals' acceptance of and demand for vaccination. However, HCP training on human papillomavirus (HPV) vaccination faces challenges in some countries, including Ethiopia, Malawi, and Uganda. This study summarizes the discussions held during the Coalition to Strengthen HPV Immunization Community Symposium in Africa, the field experiences of co-authors, and expert opinions to inform its findings. Key challenges faced in these countries are maintaining regular and comprehensive HCP training, ensuring continuity due to staff turnover, reaching all health facilities, and including teachers as key mobilizers. Funding constraints, limited communication materials, and human resource shortages can further impact training effectiveness. Recommendations for strengthening HCP training on HPV vaccination programmes include providing adequate training to all HCPs, refresher training, including private sector HCPs and teachers, leveraging local training institutions, and integrating HPV vaccine training into pre-service HCP academic curricula. These actions would be essential for improving HPV vaccine coverage and working towards cervical cancer elimination goals.

Overview of CHIC symposia series: Summary of Africa and South Asia symposia

This article presents an overview of the main challenges and lessons learned that were presented during the symposia organized by the Coalition to Strengthen the HPV Immunization Community (CHIC) in Africa and South Asia in 2022. Discussions at these meetings revolved around introduction, planning, implementation, and sustainability of HPV prevention and control programmes, with a particular focus in HPV immunisation, as well as cervical cancer screening in South Asian countries. This article also discusses the recently endorsed off-label single-dose HPV vaccination schedule and its potential impact on programme delivery and access. Furthermore, it highlights the importance of intersectional collaboration, effective communication and advocacy strategies, and the need for robust health information systems. Some of the critical factors identified for reducing the burden of cervical cancer in low- and middle-income countries (LMICs) included strategies for increasing access and coverage, addressing vaccine hesitancy, and building capacity among health care providers. The symposia emphasized the importance of face-to-face interactions for collaboration and decision making, with live translation services enabling full participation by stakeholders from diverse backgrounds. The paper concludes with a call for continued collaboration to make progress in reducing the burden of cervical cancer in LMICs.

Status of HPV disease and vaccination programmes in LMICs: Introduction to special issue

Sexually transmitted human papillomavirus (HPV) infections are extremely common in both men and women and while most will clear naturally, some may progress to cervical cancer and other cancers. Despite the availability of prophylactic vaccines and well-established screening and treatment practices, the global burden of HPV-related disease remains high, particularly in low-and-middle-income countries (LMICs). We outline the current global epidemiology of cervical cancer disease incidence and mortality, with the highest burden in Africa and Asia. As part of a strategy to eliminate cervical cancer as a public health problem, the WHO recommends a 3-fold approach combining the use of prophylactic vaccines with cervical cancer screening and treatment. This overview focuses on the globally available HPV vaccines and current status of vaccine introduction in LMICs. We describe decreased HPV vaccination coverage in recent years and highlight the need for emphasis on new vaccine introductions and existing vaccine programme strengthening in order to reach goals for the elimination of cervical cancer as a public health problem. It is estimated that US$3.20 will be returned on each dollar invested in cervical cancer prevention efforts through 2050 [1]. Success for these initiatives centers on strategic vaccine delivery and collaborations that foster political support and engagement with civil society organisations and educational sector stakeholders. Recent increases in vaccine supply and single-dose efficacy evidence pave the way for cervical cancer elimination through vaccination coupled with screening and treatment. Subsequent manuscripts in this supplement will outline case studies and lessons from two symposia held in Africa and South Asia by the Coalition to Strengthen the HPV Immunization Community in 2022 including evidence for a one-dose strategy, the challenges of maintaining vaccine programmes during the COVID-19 pandemic, and progress in cervical cancer screening programmes.

Routine HPV vaccination: Reflection on delivery strategies based on countries’ experiences

Despite the introduction of the human papillomavirus (HPV) vaccine in many low- and middle-income countries (LMICs), countries are still struggling to maintain HPV vaccination coverage and manage sustainable delivery strategies. This article explores the challenges and effective strategies for HPV vaccine delivery in LMICs, with a focus on reflecting upon current HPV vaccine delivery strategies in the World Health Organization (WHO) HPV vaccine introduction guidelines to align with practical implementation experiences. The article utilizes presentations and discussions from Coalition to Strengthen the HPV Immunization Community (CHIC) symposia, field experiences of program implementers who participated in the meeting and immunization expert opinions, to inform its findings. Several countries are spotlighted for their delivery strategies. These include routinized campaign mode vaccinations at schools in The Gambia, Zambia, and Ethiopia; routine health facility services in Tanzania, Kenya, and Maldives; and outreach strategies targeting out-of-school girls. By evaluating these diverse strategies, the article suggests a need to delve deeper and build an understanding of the routinized campaign mode of HPV vaccine delivery, and advocates for expanding the scope of delivery strategies and consequently updating the WHO HPV vaccine delivery guidelines in line with the evolving landscape of HPV vaccination delivery to ensure comprehensive, cost-effective, and sustainable programs in LMICs.

Case studies on the progress of cervical cancer screening programs in Bhutan, India, and Türkiye

International stakeholders gathered in New Delhi, India, in December 2022 to share experiences on human papillomaviruses (HPV) prevention and control strategies. As part of a supplementary publication from the meeting proceedings, this paper describes secondary HPV prevention strategies highlighting the varying degrees of progress and challenges through case studies from Bhutan, India, and Türkiye. India has implemented national screening guidelines, primarily using visual inspection with acetic acid (VIA), but achieving a low coverage rate of 1.9% (2022). In contrast, Bhutan and Türkiye have redesigned and established HPV-based cervical screening programs targeting women aged 30-65, achieving 77% (2022) and 95% (2019) coverage among women ever screened, respectively. Lessons learned include utilising patient health information management systems, analysing optimal context-specific HPV testing strategies and ensuring use and continuous supply of clinically validated HPV tests.

A national survey on HPV vaccination status among 42,800 female physicians and nurses in China, 2021

Human papillomavirus (HPV) vaccination is the most effective method to prevent cervical cancer. This study aimed to investigate the status of HPV vaccination and associated factors among Chinese females. Between January and March 2021, we conducted a large national survey among female doctors and nurses in 181 public tertiary hospitals across all 31 provinces of China. In the survey, we asked three questions: "Have you ever received an HPV vaccination? If yes, what type and in which year?" We described and compared the proportion of vaccination coverage according to occupation, age, geographic region, education, marital status, among other factors. Among 42,800 participants, 6185 (14.45 %) reported receiving HPV vaccination. Physicians showed a slightly higher vaccination rate (2064/13,804; 14.95 %) than nurses (4121/28,996, 14.21 %). Factors significantly associated with higher vaccination rates included younger age, being never married or divorced, higher education, better self-reported health status, residing in the western region, working in Obstetrics and Gynecology or Surgery departments, working at cancer hospitals, and being nulliparous. Regarding vaccine types, the 4-valent vaccine accounted for 50.3 %, followed by the 9-valent (33.7 %), imported 2-valent (16.0 %). Understanding the characteristics of the likelihood of receiving HPV vaccination among female physicians and nurses in China indicates their awareness of the risk for cervical cancer, which could help us better develop primary prevention strategies.

Exploring preventive care practices among unvaccinated individuals in the United States during the COVID-19 pandemic

Building on a Canadian study associating unvaccinated individuals to increased car accidents, we examined the relationship between COVID-19 vaccination status and US preventive care practices. We queried the 2021 National Health Interview Survey. First, we fitted a model to identify respondent-level factors associated with receipt of at least one COVID-19 vaccination. Second, we fitted a survey-weighted logistic regression model adjusted for respondent-level characteristics to examine whether the receipt of at least one COVID-19 vaccination predicted the receipt of preventive care services. Preventive care services assessed included serum cholesterol, glucose, and blood pressure measurements, as well as guideline-concordant cancer screening including breast, cervical, colorectal, and prostate cancer screening. Factors predicting receipt of COVID-19 vaccination were age (adjusted Odds Ratio (aOR) 1.03; 95 % confidence interval (CI) [1.03-1.03]), Hispanic (aOR 1.25; 95 % CI [1.08-1.44]), and non-Hispanic Asian (aOR 3.52; 95 % CI [2.74-4.52]) ethnicity/race, and history of cancer (aOR 1.61; 95 % CI [1.13-2.30]). Unvaccinated respondents were less likely to have received serum cholesterol (aOR 0.69; 95 % CI [0.50-0.70), serum glucose (aOR 0.65; 95 % CI [0.56-0.75]), or blood pressure measurements (aOR 0.47; 95 % CI [0.33-0.66]); and were less likely to have received breast cancer (aOR 0.35; 95 % CI [0.25-0.48]), colorectal cancer (aOR 0.52; 95 % CI [0.46-0.60]) and prostate cancer screening (aOR 0.61; 95 % CI [0.48-0.76]). There was no significant association between unvaccinated respondents receiving cervical cancer screening (aOR 0.96; 95 % CI [0.81-1.13]; p = 0.616). Non-receipt of COVID-19 vaccination was associated with non-receipt of preventive care services including cancer screening. Further studies are needed to assess if this association is due to system-level factors or reflects a general distrust of medical preventive care amongst this population.

Public health impact and cost-effectiveness of a nine-valent gender-neutral HPV vaccination program in France

In France, 9-valent HPV vaccination is recommended routinely for 11-14-years-old girls and as catch-up for 15-19-years-old girls. Recently, recommendation for gender-neutral vaccination (GNV) has been approved. The objectives of the study were to assess the public health impact and cost-effectiveness of a 9-valent GNV compared with girls-only vaccination program (GOV). A published HPV disease transmission dynamic model accounting for herd protection effects with a 100-year time horizon was adapted and calibrated to French data. Epidemiological and economic outcomes included disease cases averted and quality-adjusted life years (QALY). Costs and incremental cost-effectiveness ratio (ICER) were measured in 2018 Euros (€). A coverage rate of 26.2% among girls and boys was assumed for the GNV program based on the current female coverage rate in France. The base case included genital warts, cervical, vulvar, vaginal, and anal cancers. Scenario analyses included all HPV-related diseases and considered higher vaccination coverage rate (60%). Deterministic sensitivity analyses on key inputs were performed. Over 100 years, GNV resulted in an additional reduction of 9,519 and 3,037 cervical cancer cases and deaths; 6,901 and 1,166 additional anal cancer cases and deaths; and a reduction of additional 1,284,077 genital warts compared with current GOV and an ICER of 24,763€/QALY. When including all HPV-related diseases, the ICER was 15,184€/QALY. At a higher coverage rate (60%), GNV would prevent 17,430 and 4,334 additional anogenital cancer cases and deaths and over two million genital warts compared with GOV with an ICER of 40,401€/QALY. Results were sensitive to a higher discount rate (6% versus 4%) and a shorter duration of protection (20 years versus lifetime). In France, GNV has a significant impact in terms of public health benefits and may be considered cost-effective compared with GOV at low and high coverage rates.

Understanding the perceptions of Chinese women of the commercially available domestic and imported HPV vaccine: A semantic network analysis

A domestic human papillomavirus (HPV) vaccine, Cecolin, that protects against HPV strains 16 and 18 was introduced to the Chinese market at a relatively low price in May 2020.This study has explored Chinese women's perceptions of both domestic and imported HPV vaccines, which differ in price and valency. Sentiment analysis and semantic network analyses were performed based on a sample of 45,729 domestic HPV vaccine-related posts from females on the Sina Weibo between April 17 and May 2, 2020. The geographic distribution was also analyzed based on the users' locations, which were retrieved from the database. Most of the posts were positive and neutral (85%), although 15% were negative (e.g., expressions of anger, sadness, fear and disgust). Semantic analyses of the negative posts revealed that Chinese women generally had positive attitudes towards the HPV vaccine and were willing to be vaccinated. However, obvious geographical variations were identified. Women who lived in economically developed areas expressed a stronger desire to obtain imported quadrivalent or nonavalent vaccines due to concerns regarding effectiveness and quality. The women expressed disgust and anger mainly regarding difficulties in making an appointment, age restrictions for the nonavalent vaccine and gender restrictions. However, the population targeted by the domestic vaccine, namely women who lived in economically undeveloped areas and had relatively low incomes, had a low awareness of the HPV vaccine. Government should provide programs, which educate females that bivalent HPV vaccine can offer protection against the majority of high-risk HPV types. Increasing awareness of the domestic vaccine among the population in economically undeveloped areas and provision of free domestic bivalent HPV vaccination/screening for low-income high-risk women would help to prevent cervical carcinoma. This issue also depends on rebuilding trust and repairing damage to the relationship between government/domestic vaccine manufacturers and the public.

HPV vaccine: Expanding indications and global disparity

Optimising HPV vaccination communication to adolescents: A discrete choice experiment

Human Papillomavirus (HPV) vaccine coverage in France is below 30%, despite proven effectiveness against HPV infections and (pre-)cancerous cervical lesions. To optimise vaccine promotion among adolescents, we used a discrete choice experiment (DCE) to identify optimal statements regarding a vaccination programme, including vaccine characteristics. Girls and boys enrolled in the last two years of five middle schools in three French regions (aged 13-15 years) participated in an in-class cross-sectional self-administered internet-based study. In ten hypothetical scenarios, participants decided for or against signing up for a school-based vaccination campaign against an unnamed disease. Scenarios included different levels of four attributes: the type of vaccine-preventable disease, communication on vaccine safety, potential for indirect protection, and information on vaccine uptake among peers. One scenario was repeated with an added mention of sexual transmission. The 1,458 participating adolescents (estimated response rate: 89.4%) theoretically accepted vaccination in 80.1% of scenarios. All attributes significantly impacted theoretical vaccine acceptance. Compared to a febrile respiratory disease, protection against cancer was motivating (odds ratio (OR) 1.29 [95%-CI 1.09-1.52]), but not against genital warts (OR 0.91 [0.78-1.06]). Compared to risk negation ("vaccine does not provoke serious side effects"), a reference to a positive benefit-risk balance despite a confirmed side effect was strongly dissuasive (OR 0.30 [0.24-0.36]), while reference to ongoing international pharmacovigilance without any scientifically confirmed effect was not significantly dissuasive (OR 0.86 [0.71-1.04]). The potential for indirect protection motivated acceptance among girls but not boys (potential for eliminating the disease compared to no indirect protection, OR 1.57 [1.25-1.96]). Compared to mentioning "insufficient coverage", reporting that ">80% of young people in other countries got vaccinated" motivated vaccine acceptance (OR 1.94 [1.61-2.35]). The notion of sexual transmission did not influence acceptance. HPV vaccine communication to adolescents can be tailored to optimise the impact of promotion efforts.

Prophylactic HPV vaccination after conization: A systematic review and meta-analysis

Human papillomavirus (HPV) vaccination is essential for cervical cancer prevention. However, the value of HPV vaccination in the context excisional treatment of high-grade cervical intraepithelial neoplasia (CIN 3) remains unclear. In this meta-analysis, three retrospective and three prospective studies, three post-hoc analyses of RCTs and one cancer registry study analysing the effect of pre- or post-conization vaccination (bi- or quadrivalent vaccine) against HPV were included after a systematic review of literature. Random-effect models were prepared to evaluate the influence of vaccination on recurrent CIN 2+. Primary end point was CIN2+ in every study. The overall study population included 21,059 patients (3,939 vaccinations vs. 17,150 controls). The results showed a significant risk reduction for the development of new high-grade intraepithelial lesions after HPV vaccination (relative risk (RR) 0.41; 95% CI [0.27; 0.64]), independent from HPV type. Due to the heterogeneous study population multiple sub analyses regarding HPV type, age of patients, time of vaccination and follow-up were performed. Age-dependent analysis showed no differences between women under 25 years (RR 0.47 (95%-CI [0.28; 0.80]) and women of higher age (RR 0.52 (95%-CI [0.41; 0.65]). Results for HPV 16/18 positive CIN2+ showed a RR of 0.37 (95% CI [0.17; 0.80]). Overall, the number of women that would have to be vaccinated before or after conization to prevent one case of recurrent CIN 2+ (NNV) is 45.5. Meta-analysis showed a significant risk reduction of developing recurrent cervical intraepithelial neoplasia after surgical excision and HPV vaccination compared to surgical excision only.

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Comparing immunogenicity of the Escherichia coli-produced bivalent human papillomavirus vaccine in females of different ages

The safety and efficacy of a recently licensed Escherichia coli (E. coli)-produced bivalent HPV vaccine have been shown. Specific antibody levels are important indicators to evaluate the efficacy of vaccination. Therefore, we compared the immunogenicity of this HPV 16/18 vaccine in females of different ages in this study. Immunogenicity of the vaccine was analyzed in the per-protocol sets for immunogenicity (PPS-I) of a phase III trial and an immune-bridging trial. The serum samples were collected at month 0 and one month after the final dose (month 7) to assess the specific IgG antibody levels by ELISA. The seroconversion rates, geometric mean concentration (GMC), and geometric mean increase (GMI) were used to assess the immunogenicity of the test vaccine. The non-linear association of antibody levels with age was estimated via natural cubic splines and the Akaike information criterion was used to assess optimal model. By combining the PPS-I data from the two trials, nearly all of the females seroconverted for both HPV types. In the 3-dose group, the GMC of IgG to both HPV types decreased with increasing age, especially in adolescent girls and young women. For HPV-16 and -18, the declining trend slowed down in women older than 32 and 35 years old, respectively. The GMI ranged from 648 to 80 for HPV-16 and from 218 to 42 for HPV-18. In the 2-dose group, the specific antibodies for HPV-16 and -18 peaked in girls aged 10 years with GMIs of 401 and 98, respectively, and then decreased with age. The E. coli-produced bivalent HPV-16/18 vaccine induced specific antibody responses in females aged 9-45 years. The antibody levels were inversely associated with age, and the declining trends slowed down in women older than 32 or 35 years for HPV-16 and -18, respectively.

Targeting key groups using a low-cost strategy to increase HPV awareness and vaccine uptake

Cost-effectiveness of the introduction of two-dose bi-valent (Cervarix) and quadrivalent (Gardasil) HPV vaccination for adolescent girls in Bangladesh

Cervical cancer is one of the most prevalent cancers in women caused by the human papillomavirus (HPV) that leads to a substantial disease burden for health systems. Prevention through vaccination can significantly reduce the prevalence of cervical cancer. The objective of this study is to evaluate the potential health and economic impacts of introducing two-dose bivalent (Cervarix) and quadrivalent (Gardasil) HPV vaccines in Bangladesh. The study uses the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess the cost-effectiveness of introducing HPV vaccination. The incremental cost-effectiveness ratios (ICERs) were estimated per disability-adjusted life years (DALYs) averted using the cost-effectiveness threshold (CET). The analyses were done from a health system perspective in terms of vaccine delivery routes. Introduction of bi-valent HPV vaccination was found highly cost-effective (ICER = US$488/DALY) at Gavi (The Vaccine Alliance for Vaccines and Immunizations) negotiated prices. The value of ICERs were US$710, US$356 and US$397 per DALY averted for school-based, health facility-based, and outreach-based programs, respectively, which is consistent with the CET range (US$67 to US$854). However, bivalent and quadrivalent vaccines at listed prices were not found cost-effective, with ICERs of US$1405 and US$3250 per DALY averted, respectively, that exceeds the CETs values. Introducing a two-dose bi-valent HPV vaccination program is cost-effective in Bangladesh at Gavi negotiated prices. Vaccine price is the dominating parameter for the cost-effectiveness of bivalent and quadrivalent vaccines. Both vaccines are not cost-effective at listed prices in Bangladesh. The evaluation highlights that introducing the two-dose bivalent HPV vaccine at Gavi negotiated prices into a national immunization program in Bangladesh is economically viable to reduce the burden of cervical cancer.

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

Cervical 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. Seven 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. Sixteen 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. Parents' 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.

HPV genotyping in biopsies of HSIL and invasive cervical cancers in women living with HIV: A cohort- and a nested -case control study

To characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women. Cohort- and nested -case control study. We characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated. Among WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3-5,2,p = 0,002), lymphocyte CD4 count < 350 cells / µL (OR 2,7 (95%IC: 2-8,5; p = 0,005), use of cART for < 18 month OR 2,2 (95%IC: 1,1-4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2-8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p < 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p < 0,001). WLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021—March 2022

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in &gt;62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2+ from childhood vaccinated women: The Trial23 cohort study

The introduction of prophylactic HPV vaccination has significantly reduced vaccine-type HPV infections and is reshaping the landscape of cervical cancer prevention. As vaccinated cohorts enter screening age, understanding the genotype-specific risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) is critical for adapting screening strategies. To compare HPV genotype-specific detection rates of histologically confirmed CIN2+ between vaccinated and unvaccinated women in Denmark's Trial23 cohort, with over seven years of follow-up. This population-based cohort study included 15,668 women born in 1994 who were offered HPV vaccination with the 4-valent vaccine in 2008 and entered Danish screening age in 2017 In our cohort, 95 % were vaccinated and 5 % were unvaccinated. The primary endpoints of this study were HPV-type-specific incident CIN2+ cases. The first histological biopsy sample diagnosed with CIN2+ in 2017-2023 was retrieved for HPV genotyping with the Seegene Allplex HPV28. Cox proportional hazards models estimated hazard ratios (HRs) for CIN2+ outcomes by hierarchically grouped HPV genotypes. Among vaccinated women, the incidence of CIN2+ was 5.3 per 1000 person-years, compared to 12.1 per 1000 person-years in unvaccinated women (HR: 0.44; 95 % CI: 0.34-0.57). Vaccination was associated with a 95 % reduction in HPV16/18-related CIN2+ (HR: 0.05; 95 % CI: 0.03-0.09). A similar, but non-significant, trend of a 32 % risk of CIN2+ for HPV31/33/45/52/58 was found, with an adjusted HR of 0.68 (95 % CI: 0.43-1.09). For CIN2+ associated with other high-risk HPV types, the HR was 0.70 (95 % CI 0.35-1.37). HPV16/18 vaccination reduced the risk of HPV16/18-related CIN2+ lesions, but a substantial burden remained from non-vaccine high-risk types. The substantial protection against HPV16/18-related CIN2+ and the consequential shift in HPV genotype distribution of CIN2+ among vaccinated women underline the need for adaptation of screening strategies.

Beyond the post: The impact of politized anti-vaccine misinformation comments and challenges of correction on social media

Despite the proven effectiveness of HPV vaccines in preventing cervical cancer, vaccination rates in the United States remain low, in part because parents' decisions are heavily shaped by misinformation encountered on social media. Using an online experimental design (N = 1039), this study investigated the effects of politized anti-vaccine misinformation comments under CDC posts on parents' vaccination hesitancy as well as the emotional mechanism of this impact. Individual's need for cognition (NFC) was also examined as a moderator. Furthermore, we explored whether CDC corrections help to mitigate these negative effects. Results showed a moderated mediation relationship. Participants exposed to politized anti-vaccine misinformation comments reported higher HPV vaccine hesitancy, with negative emotions toward the original post mediating this association. However, this pattern was observed only among participants with low to medium levels of NFC. For individuals with high NFC, the relationship between negative emotions and vaccine hesitancy, as well as the mediation effect of negative emotions, were not significant. Corrections from the CDC did not help decrease the negative emotions and HPV vaccine hesitancy. This study extends prior research by investigating the effectiveness of second-layer correction comments, an increasingly common but underexamined form of misinformation correction strategy in the current interactive social media environments.

Evaluation of the safety profile of the quadrivalent vaccine against human papillomavirus in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia

Cervical cancer eradication is one of the main goals for 2030 by the World Health Organization, which can only be achieved with high vaccination rates against Human Papilloma Virus. In Colombia, more and better scientific evidence is required to increase confidence in vaccination. The objective of this study is to evaluate the safety profile of the quadrivalent vaccine against HPV in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia. We designed a cohort study based on national HPV vaccination records and incident diagnostic data for the diseases of special interest during 2012 and 2021. We included adolescent women between 9 and 19 years old and compared vaccinated and non-vaccinated cohorts using an Inverse Probability of Treatment Weighting (IPWT) method for each scenario disease and follow-up period (180 and 360 days). The Odds Ratio (OR) of developing diseases of interest was estimated during two follow up periods, 180 and 360 days after the follow-up index date (Vaccination Day). The OR for developing rheumatoid arthritis was 4·4; CI95% (1·74 - 11·14), juvenile idiopathic arthritis was 2·76 IC95% (1·50 - 5·11), idiopathic thrombocytopenic purpura was 2·54 IC95% (1·28 - 5·02) and thyrotoxicosis was 2·86 IC95% (1·03 - 7·95), when comparing the vaccinated versus unvaccinated population. However, the temporal distribution of cases incident did not reveal a clear difference between the cohorts, since the rate of appearance of new cases has a constant linear behavior for the two groups. For rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic thrombocytopenic purpura, and thyrotoxicosis; the application of the vaccine had an effect on the development of the disease. Nevertheless, our results should be interpreted with caution and be further studied, considering that the biological plausibility of the events occurred without a clear temporal pattern in relation to the exposure to the vaccine.

A single dose of quadrivalent human papillomavirus (HPV) vaccine is immunogenic and reduces HPV detection rates in young women in Mongolia, six years after vaccination

Emerging observational evidence suggests a single-dose of human papillomavirus (HPV) vaccine may be protective against vaccine-targeted HPV infection and associated cervical dysplasia. We aimed to demonstrate whether a single dose of quadrivalent HPV (4vHPV) vaccine was immunogenic and reduced HPV detection rates in young women in Mongolia. We also assessed knowledge and attitudes regarding HPV and the HPV vaccine. A retrospective paired cohort study was undertaken to evaluate the effect of a single dose of 4vHPV, given at age 11-17 years in 2012, on HPV detection rates, when compared with unvaccinated women. Real time PCR was performed on self-administered vaginal swabs for HPV detection. An immunological analysis detecting neutralising antibodies (NAb) to high-risk HPV (HRHPV) genotypes 16 and 18 was performed on sera from a subset of 58 participants. Questionnaires evaluated knowledge, attitudes and self-swab acceptability. A total of 475 women (mean age 20.4 years ± 1.6) were recruited; 118 vaccinated and 357 unvaccinated women. The prevalence of vaccine-targeted HRHPV16 and 18 was reduced by 92% (95%CI 44-99%) in the vaccinated (1·1%) compared with the unvaccinated (15.4%) group. The percentage of non-vaccine HPV genotypes was similar between vaccinated (26.5%) and unvaccinated (26.7%) groups. Approximately 90% and 58% of vaccinated women remained seropositive after six years for HRHPV16 and 18, respectively, with neutralising antibody levels 5- and 2-fold higher than unvaccinated women (p < 0.001). One dose of 4vHPV vaccine reduces vaccine-targeted HPV genotypes, six years following vaccination, with high levels of HR genotype seropositivity among young Mongolian women.

Effect of a school-based educational intervention on HPV and HPV vaccine knowledge and willingness to be vaccinated among Chinese adolescents : a multi-center intervention follow-up study

Middle school students are recommended as the primary target population for human papillomavirus (HPV) vaccination. This study aimed to assess HPV and HPV vaccine knowledge, and to evaluate the effect of a school-based educational intervention, immediately and one year later, on HPV knowledge and vaccine acceptability among adolescents in mainland China. A school-based interventional follow-up study was conducted in seven representative cities in mainland China from May 2015 to May 2017. "Train-the-trainer" strategy was employed to educate school teachers in this study. Students aged 13 to 14 years old were assigned to intervention classes and control classes. All students were required to complete the baseline questionnaire. Students in the intervention classes were given a 45-minute lecture regarding HPV and HPV vaccine knowledge and were then asked to complete a post-education questionnaire. One year later, all students were asked to complete the post-education questionnaire again. Baseline HPV knowledge was low among Chinese adolescents, with only 12.6% and 15.7% of students having heard of HPV and HPV vaccines, respectively. After the intervention, the level of HPV-related knowledge increased immediately, and students with higher knowledge levels of HPV and HPV vaccines were more willing to get vaccinated. One year after the intervention, the knowledge of HPV and HPV vaccines was dramatically diminished. However, knowledge was significantly higher in intervention classes compared to control classes. Knowledge and awareness of HPV and vaccination are generally deficient among Chinese adolescents. School-based health education was very effective in improving awareness and positive attitudes about HPV and HPV vaccines within a short time. Integrating health education on HPV into the existing school-based sexual health curriculum could be an effective way to increase HPV vaccination coverage and help to eliminate preventable HPV-associated cancers in China.

Integrating HPV vaccination programs with enhanced cervical cancer screening and treatment, a systematic review

A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations.

Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009–2017

To assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14-23 years and to estimate the incidence of GW in the whole population aged from 14 to 65. Population-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID). All subjects aged 14-65 years residing in the Valencia Region during 2009-2017 (n = 4,492,724), including a cohort of 563,240 females aged 14-23 years followed-up for the vaccine effectiveness (VE) estimations. Incident cases of GW defined as the first activation of GW-related codes (ICD-9-CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) × 100 by a negative binomial Bayesian model. There were 23,049 cases of GW in the overall population and 2,565 in the females' cohort 14-23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21-69.99) in the population overall, being higher in men (72.73; 95% CI 71.45-74.04). The IR of GW was 104.08 (95% CI 100.79-108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68-79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine. A complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girls.

Human papillomavirus type 16 and 18 viral clearance and progression to precancer among women aged 18–25 years enrolled in the Costa Rica HPV prophylactic vaccine trial (CVT)

New approaches to control HPV infections and prevent progression to cervical precancer are needed. We investigate the probability of viral clearance and progression to cervical precancer in women infected with HPV16/18 without evidence of precancer at study enrollment to inform research efforts targeted at reducing cervical cancer. We included 530 women aged 18-25 who tested HPV16/18 DNA-positive and did not have cytological evidence of high-grade-squamous-intraepithelial-lesion (HSIL) at enrollment in CVT. At each visit, clinicians collected cervical cells for cytology and HPV-DNA testing. Those with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. We estimated the probability of HPV clearance (loss of detection) and progression to intraepithelial neoplasia grades 2 or 3 or worse (CIN2+, CIN3+) based on histological findings by expert pathologists over 4-years of follow-up. At enrollment, there were 550 prevalently detected HPV16 and/or HPV18 infections among 530 women without cytologic HSIL. Corresponding probabilities of HPV16 and HPV18 clearance were 68.5 % (95 %CI 63.6 %-73.0 %) and 85.0 % (78.6 %-90.1 %) by 24-months and 82.1 % (78.0 %-85.7 %) and 90.2 % (84.7 %-94.2 %) by 48-months after initial detection. Risk of clearance of prevalently detected HPV16 and HPV18 infections decreased with increasing age by 12-, 24-, 36-, and 48-months after initial detection (p Among young adult women without evidence of HSIL by cytology, clearance of prevalently detected HPV16/18 infection is a common event, and progression to precancer occurs infrequently but in a sizeable proportion of those with prevalent infection.

Facilitators and barriers to implementation of HPV vaccination in Tanzania: a mixed-methods study exploring perspectives from national, subnational, and community stakeholders, 2018–2023

Cervical cancer is the fourth most common cancer among women globally, disproportionately affecting those in low- and middle-income countries (LMICs). In 2020, World Health Organization (WHO) Member States endorsed the 2030 Global Strategy toward Elimination of Cervical Cancer, recommending expanded access to human papillomavirus (HPV) vaccination. However, gaps remain in understanding how LMICs can sustain high HPV vaccine coverage. Tanzania, an early adopter among LMICs, introduced HPV vaccination into the national immunization schedule for 14-year-old girls in 2018 and achieved >90 % two-dose coverage by 2023. This study evaluated HPV vaccine program implementation in Tanzania, capturing stakeholder perspectives on barriers, facilitators, and recommendations. Stakeholders were interviewed in April 2024 in a concurrent mixed-methods evaluation. Participants included national and subnational immunization staff (n = 18), and health workers, teachers, and community influencers (n = 80). Four of 31 regions were purposively selected based on criteria including first-dose HPV coverage (2020-2022) and urban/rural distribution. Two health facilities were randomly selected from a list of facilities in each region, along with two schools administering the vaccine from each facility's catchment area. Quantitative data were analyzed descriptively in STATA v.18, and qualitative data analyzed in ATLAS.ti Web (v19.3.1). Political support, quality improvement cycles, and integration with existing systems were identified as contributing to program success. Funding gaps and staff shortages-particularly in regions with low HPV vaccination coverage-were among the reported barriers, along with poor coordination between health and education sectors and low community awareness. Recommendations included increasing government funding, strengthening cross-sector collaboration, training stakeholders, and expanding dissemination channels to improve demand and address vaccine hesitancy. Tanzania's experience offers lessons for HPV vaccination in similar contexts. Addressing key barriers through increased funding, improved coordination, and enhanced community engagement could improve HPV vaccination implementation in Tanzania and elsewhere, contributing to global cervical cancer elimination.

Predicted impact of HPV vaccination and primary HPV screening on precancer treatment rates and adverse pregnancy outcomes in Australia 2010–2070: Modelling in a high income, high vaccination coverage country with HPV-based cervical screening

Treatment of cervical precancer may be associated with an increased risk of adverse pregnancy outcomes. Australia introduced routine quadrivalent HPV vaccination (HPV4) in 2007, switching to nonavalent vaccination (HPV9) in 2018, and 5-yearly HPV screening in December 2017. We estimated the impact of HPV vaccination and HPV screening on precancer treatments, and thus on future preterm births (PTBs) and low birth weight (LBW) infants. Using a model of HPV infection, natural history, cervical screening and precancer treatment, coupled with a Monte-Carlo model of fertility and obstetric outcomes, we estimated rates and numbers of precancer cervical treatments, PTBs and LBW infants in women with singleton pregnancies in Australia from 2010 to 2070. These outcomes were estimated for four scenarios: i) a base scenario, assuming the current HPV screening and vaccination programs; and three alternative scenarios: ii) future twice-lifetime screening in cohorts offered HPV9; (iii) no HPV vaccination program introduced (counterfactual); and (iv) HPV4 was never replaced with HPV9 (counterfactual). Precancer treatment rates are predicted to decrease by 82 % between 2010 and 2070 in the context of HPV9 vaccination and ongoing 5-yearly screening, with an additional 42 % reduction by changing to twice-lifetime screening in HPV9 cohorts. An estimated 800,388 treatments would be averted over 2010-2070 by HPV9 compared to no vaccination, 80 % of these due to vaccine protection against HPV16/18. These treatment reductions will result in 22,441 (32,011) fewer PTBs (LBW infants) over 2010-2070 due to vaccine protection against HPV16/18, and a further 4359 (6298) due to vaccine protection against HPV31/33/45/52/58. An additional 3174 (4621) events would be averted with future twice-lifetime screening in HPV9 cohorts. This analysis demonstrates that the benefits of HPV vaccination programs extend beyond prevention of HPV-related disease. HPV vaccination will reduce PTBs and LBW infants, with a further reduction with future twice-lifetime screening for HPV9 cohorts.

HPV vaccination coverage among children and adolescents in Greece using national prescription data

To eradicate cervical cancer, the World Health Organization (WHO) targets 90 % human papillomavirus (HPV) vaccination coverage in girls by the age of 15 until 2030. In Greece, data regarding how close the country is to meeting this target, is completely lacking. To assess annual HPV vaccination coverage among individuals aged 9-15 years in Greece (2022-2024). This is a retrospective, population-based cohort study using the Greek National Electronic Prescription Database to record all HPV vaccine doses dispensed from 1/1/2019 to 31/12/2024. The annual vaccination coverage was estimated as the proportion of eligible population receiving at least one dose or the full vaccination scheme from January 1st, 2019, through December 31st of the respective reference year. Full vaccination scheme by age 15 was defined - according to national recommendations - as two doses at a minimum interval of 6 months. From 2022 to 2024, the proportion of individuals 9-15 years old, who appropriately initiated vaccination increased from 34.7 % (2022) to 41.4 % (2024) in girls and from 10.8 % (2022) to 31.4 % (2024) in boys. The proportion of children who initiate HPV vaccination at the age of 9, increased from 3.5 % and 3.4 % in 2022 to 8.0 % and 7.4 % in 2024 in girls and boys respectively. Among girls turning 15, appropriate vaccine initiation rate marginally exceeded 63.0 % throughout the study period while full vaccination coverage increased from 47.7 % in 2022 to almost 52.5 % in 2024. Despite notable improvements in HPV vaccination uptake among adolescents in Greece between 2022 and 2024, coverage levels remain suboptimal relative to the WHO's 90 % target. Limited early initiation despite national recommendations starting at age 9, highlight the need for targeted strategies to promote timely HPV vaccination and accelerate progress toward elimination goals.

Knowledge and acceptability of male HPV vaccination among young people and community stakeholders in northwest Tanzania: social sciences in the Add-Vacc trial

Human papillomavirus (HPV) and related diseases are global health concerns affecting both males and females. Tanzania introduced two-dose HPV vaccination for 14-year old girls in 2018. The Add-Vacc trial in rural northwest Tanzania is evaluating the impact of adding one-time, single-dose HPV vaccination for 14-18-year-old boys to the national programme for girls on HPV population prevalence. As this is the first time HPV vaccination has been offered to adolescent males in Tanzania, acceptability of boys' HPV vaccination among adolescents and community stakeholders was assessed. Qualitative data were collected between July 2023-May 2024 through: 1) rapid ethnography; 2) rumours tracking using an electronic tool piloted during the study; 3) in-depth interviews with in- and out-of-school boys who accepted or declined vaccination; 4) key informant interviews with vaccination stakeholders including parents, teachers, health workers, and community leaders; and 5) focus group discussions with stakeholders and vaccination-age boys and girls. Data were coded using Nvivo12 and analysed thematically. Messaging on HPV-related complications beyond cervical cancer motivated parental and adolescent support for vaccinating both boys and girls. Framing male HPV vaccination as a gender equity issue and highlighting the economic burden of illness emerged as important themes. Participants emphasised the need for trusted, locally recognised messengers to convey information. Parents and peers were key influencers for adolescents, while health workers and religious/community leaders influenced parents. Some parents and adolescents who initially declined vaccination reported they later accepted it after having time to reflect and seeing vaccinated boys experienced no adverse effects. Single-dose HPV vaccination of males was generally acceptable across all study groups. Ongoing, dynamic community engagement and open dialogue about the full spectrum of HPV-related sequalae and HPV vaccination for both genders are essential to building trust and improving understanding and acceptability of HPV vaccination targeting boys and girls in this Tanzanian context.

HPV vaccination coverage and determinants in adolescent girls with disability: a scoping review

Human papillomavirus (HPV) vaccination has been scaled up in many countries in response to global calls for cervical cancer elimination. Adolescent females with disability face significant inequities when accessing healthcare and may be overlooked in vaccination programs and campaigns. We undertook a scoping review to examine HPV vaccination coverage and key enablers and barriers for this population. Our secondary aim was to describe the methodologies used to study this population to guide future research. A scoping review was conducted using the Joanna Briggs Institute guidelines. Four databases were searched for English-language peer-reviewed literature examining HPV vaccination amongst adolescent girls with disability in low-, middle- and high-income countries, with no restrictions on timeline or context. HPV vaccination coverage rates and study methodologies were extracted into tables, and key enablers and barriers were mapped to the socio-ecological framework. Twenty-four studies were included. Studies reported a wide range in HPV vaccination coverage from 22.9 % to 87.4 % and a variety of research methods were used to derive these estimates. Slightly more than half of studies (n = 6/11) which included a comparison cohort reported lower HPV vaccination coverage rates in adolescent females with disability compared to those without disability. Included studies found individual and interpersonal level enablers and barriers at a greater frequency compared to organisational, environmental and policy level determinants. The current literature shows disparities in HPV vaccination coverage and identifies a diverse range of enablers and barriers for adolescent girls with disability, using multiple research methodologies. Efforts are needed to incorporate theoretical frameworks to guide research, extend research to low-resource countries and implement population level registry data sets.

HPV burden in Armenia among unvaccinated women: a series of cross-sectional population-based prevalence surveys

In 2017, Armenia introduced a national human papillomavirus (HPV) vaccination programme with a quadrivalent vaccine at age 14 years. Successful implementation of the programme was affected by social media campaigns aiming to discredit its efficacy and safety, the COVID-19 pandemic, and local armed conflicts. To support national public health stakeholders, we initiated a series of studies to provide local evidence on the burden of HPV infection. Two cross-sectional HPV prevalence surveys among unvaccinated birth-cohorts of women were conducted: a urine-based survey (UBS) targeted women aged 17-21 years, and a cell-based survey (CBS) targeted women aged 21-39 years. In addition, we collected a series of invasive cervical cancer (CC) case laboratory samples to assess the attributable proportion of high-risk (HR) HPV types to estimate the impact of HPV vaccination in Armenia. In the UBS and the CBS, 2485 and 3017 women were included, respectively. In the UBS, 110 (4.5 %) women were positive for any HPV type, 72 (2.9 %) of which were HR HPV and 29 (1.2 %) were HPV16/18. In the CBS, 553 (18 %) were positive for any HPV type, 326 (11 %) of which were HR HPV, and 99 (3.3 %) were HPV16/18. In the CC series, HPV16/18 accounted for 71 % of all HR HPV infections, HPV 31, 33, 45, 52, and 58 accounted for an extra 18 %. The remaining HR types accounted for 11 % of all CC infected by HR HPV. The corresponding predicted cumulative 10-year CC incidence among 20-24, 25-34, and 35-44-year age group, was 0.3 %, 1.3 %, and 3.8 %, respectively. Our findings provide a picture of the HPV infection and future cervical cancer burden among unvaccinated young and adult women in urban areas of Armenia and can inform context-specific vaccination and screening policies.

Cost-effectiveness of different HPV vaccination strategies for cervical cancer prevention in South Africa

Most cervical cancers can be prevented by population-wide vaccination of pre-adolescent girls with highly efficacious HPV vaccines. In South Africa, first-dose coverage of bivalent HPV vaccination among girls aged 10 is ∼80 %. We investigated the additional impact and cost-effectiveness of different bivalent and nonavalent vaccination strategies among the general population and women with HIV (WHIV). We used an individual-based, population-level model for HPV and HIV transmission in South Africa to estimate the epidemiological impact of HPV vaccination. The costs of interventions in the cervical cancer care cascade are estimated in 2024 USD based on resource use and prices obtained from research studies. To estimate cost-effectiveness of different bivalent strategies, we calculated the median cost per disability adjusted life-year averted (DALY) between 2024 and 2120 and compared it to an opportunity cost (OC) threshold of USD 3015. We calculated a threshold price at which nonavalent vaccination will be cost-effective in South Africa. Current interventions are projected to reduce age-standardised cervical cancer incidence from 54 to 12 per 100,000 women by 2120. Increasing girl-only bivalent coverage to 90 % would prevent an additional 5 % of cases and be cost-saving. Gender-neutral vaccination at 80 % coverage would yield similar impact, with a USD/DALY averted of USD 2782 compared to girls-only vaccination. Vaccinating WHIV up to age 45 could prevent 10 % of cervical cancer cases in this group and remains cost-effective. The nonavalent vaccine would be cost-effective if priced below USD 40 per dose. Enhanced HPV vaccination strategies-including higher coverage, gender-neutral programs, and targeted vaccination of WHIV-are cost-effective in South Africa. However, no vaccination strategy alone will reach elimination, which will require integrated approaches combining vaccination with cervical cancer screening and treatment.

Meeting report: Considerations for trial design and endpoints in licensing therapeutic HPV16/18 vaccines to prevent cervical cancer

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12-13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections.

Evolving trends in HPV vaccination coverage among women aged 9–45 in Chengdu, China: insights from 2017 to 2023

Chengdu, China, is facing an increasing burden of cervical cancer. Although human papillomavirus (HPV) vaccines have been introduced in China since 2016, vaccination coverage remains suboptimal, and data on regional disparities are limited. In 2021, Chengdu implemented a subsidized HPV vaccination program targeting girls aged 13-14 years. This study aims to evaluate HPV vaccination coverage among females aged 9-45 years in Chengdu from 2017 to 2023, stratified by age group, geographic area, and vaccine type, and to examine changes in vaccination coverage among girls aged 13-14 years following the city's enrollment in the pilot subsidy program. HPV vaccination data were sourced from the Sichuan Provincial Immunization Information System. Descriptive analyses assessed annual and cumulative vaccination coverage from 2017 to 2023 among females aged 9-45 years in Chengdu. An interrupted time series (ITS) analysis using a segmented regression model (SRM) was conducted to quantify changes in vaccination rates following program implementation among girls aged 13-14 years. From 2017 to 2023, first- and full-dose HPV vaccination coverage among females aged 9-45 years in Chengdu showed significant upward trends across age groups, geographic areas, and vaccine types. By 2023, cumulative first-dose coverage reached 34.17 %, with full-dose coverage at 24.40 %. Notably, vaccination rates for girls aged 13-14 years exhibited markedly higher first- and full-dose coverage compared to pre-program levels (β = 1.899, p-value = 0.002; β = 4.859, p-value <0.001, respectively). Following the HPV vaccination program in Chengdu, the vaccination rate for girls aged 13-14 years significantly increased. However, the overall vaccination rate for women aged 9-45 years remains relatively low, particularly among certain subpopulations. To enhance overall vaccination rates, strategic priorities should include targeted interventions for subpopulations with suboptimal coverage, expansion of pilot programs, and stronger political commitment to integrating the HPV vaccine into the National Immunization Program.

Effective strategies in human papillomavirus (HPV) vaccination interventions to increase uptake in rural, low socioeconomic, indigenous and migrant populations: A scoping review

Human Papillomavirus (HPV) vaccination is a key strategy to reduce HPV-related cancers such as cervical cancer. Rural, low socioeconomic status, ethnic minority, Indigenous and migrant populations often experience inequity when accessing HPV vaccination. This scoping review searched six databases for intervention studies which measured the uptake of HPV vaccination of rural, low SES, ethnic minority, Indigenous or migrant adolescent-young adult population. Strategies were categorised according to their setting: clinical, school-based, community, or a combination of one or more of these settings. Effective strategies from 46 studies which increased equity in HPV vaccination uptake included: (1) Information disseminated through handouts, multilingual material, and health care conversations using presumptive language; (2) 'Prompting' using a practice-wide coordination to flag patient records, remind patients, and alert them of their appointment for HPV vaccination; (3) Health Care Professional (HCP) training to communicate information effectively about HPV vaccination, and include HCP champions as HPV vaccination advocates; (4) School-based programs, using strategies such as on-site vaccination, student-engagement fetes and partnership with clinics to increase HPV vaccination 'catch-up'; (5) Family-centred care to motivate HPV vaccination for cancer prevention. Although interventions demand preparation and coordination to initiate, they can positively influence the uptake of HPV vaccination. There are a wide range of effective strategies to increase equity in HPV vaccination in the rural, low SES, ethnic minority, Indigenous and migrant adolescent-young adult populations. Future evaluation of effective strategies could explore their sustainability and long-term implementation in interventions.

“The only vaccine that we really question is the new vaccine”: A qualitative exploration of the social and behavioural drivers of human papillomavirus (HPV) vaccination in Tonga

Human papillomavirus (HPV) vaccination is crucial for cervical cancer elimination, particularly in the Pacific where screening and treatment are limited. The HPV vaccine was introduced through schools in Tonga in November 2022 for adolescent girls. Despite high routine childhood vaccine coverage in Tonga, uptake of the HPV vaccine has been slow. This study explored the social and behavioural drivers of HPV and routine childhood vaccination in Tonga to inform tailored strategies to increase vaccine uptake. We conducted qualitative interviews and focus groups in Nuku'alofa between June and October 2023 with parents (n = 32), adolescent girls (n = 24), teachers (n = 15), nurses (n = 7), and immunization staff (n = 5). Data were analysed thematically and mapped to the World Health Organization's Behavioural and Social Drivers of vaccination framework. Parents, teachers, and girls had limited knowledge of the HPV vaccine. Some feared it would encourage promiscuity or impact fertility. While trust in routine childhood vaccines was high, participants felt the COVID-19 pandemic had reduced confidence in new vaccines. Some vaccinated girls felt the HPV vaccine offered protection whereas others were afraid of side effects. Practical barriers included non-standardised consent forms that had to be returned to schools, the vaccine rollout timing, and school participation. Providing youth, parents and teachers with accurate, culturally appropriate information and supporting teachers to discuss vaccination and facilitate consent may improve HPV vaccine uptake in Tonga.

Human papillomavirus awareness, vaccination rate, and sociodemographic covariates of vaccination status in a low-income country: A cross-sectional study in the rural Busoga region of Uganda

We aimed to describe Human Papillomavirus (HPV) and HPV vaccine awareness. Moreover, we estimated a vaccination rate for the accumulated target group of 10 to 18-year-old girls based on a maternal approach. Finally, we evaluated sociodemographic covariates of HPV vaccination status in rural Uganda. Via questionnaires filled by instructed research assistants, women above 18 years were included via randomisation schemes in the rural Busoga Region in Eastern Uganda. In total, 585 participants were included. One out of eight (12.6 %) had heard about HPV before. More than one-third (36.5 %) had heard about the HPV vaccine. Almost all (94.9 %) would vaccinate their daughter against HPV if they had one. Most participants (61.9 %) believed the vaccine prevents cervical cancer, although more than one-third (34.9 %) did not know this. Altogether, 213 mothers to 388 daughters aged 10 to 18 years were registered. Of these, 49 to 63 (12.6 % - 16.2 %) daughters were single-dose HPV vaccinated, and 79 (20.4 %) daughters were double-dose vaccinated, yielding an any-dose HPV vaccination rate of 33.0 % - 36.6 %. Lastly, 51 (13.1 %) of the daughters had a vaccination card confirming the vaccine. Living in a peri-urban district was a significant covariate of having a double-vaccinated daughter compared to rural districts. We found low awareness levels of HPV and the HPV vaccine, but indications of a favourable attitude toward the vaccine. The any-dose vaccination rate was 33 % - 36,6 % with indications that a future HPV awareness- and vaccine campaign should focus on the most peripheral districts of rural Uganda.

Intervention-amenable factors associated with lack of HPV vaccination in Kenya: Results from a large national phone survey

Coverage of human papillomavirus (HPV) vaccination remains suboptimal in many countries, but the determinants are not well-understood particularly in low- and middle-income countries. We undertook a random digit dialed phone survey across Kenya between July-October 2022, with parents/caregivers of preadolescent girls, to identify intervention-amenable factors associated with respondents' daughter's HPV vaccination status. Informed by the World Health Organization Behavioral and Social Drivers of Vaccination framework, we collected information about respondents' knowledge about and hesitancy toward HPV vaccine, perceived risk of cervical cancer, social norms around HPV vaccination, trust in institutions, and access to HPV vaccination services. 1416 parents/caregivers completed the survey (97.4 % of those eligible), of whom 38.2 % said that age-eligible girl(s) in their household had received any doses of the HPV vaccine. Knowledge/perceptions: In multivariable models adjusted for sociodemographic characteristics, respondents with less HPV vaccine hesitancy and fewer concerns about safety were more likely to have vaccinated daughter(s), as were those with greater knowledge about HPV vaccine and knowing someone who had died from cervical cancer. Social norms: Having spoken with others about HPV vaccination, although reported by less than half of respondents, and believing that other parents have vaccinated their daughters were associated with having vaccinated daughter(s). Respondents with more trust in information about HPV vaccination from health systems, and with higher trust in institutions, had greater odds of having vaccinated daughter(s). Access: One-fifth of respondents had experienced, or anticipated experiencing, challenges accessing HPV vaccination services, and these respondents had approximately half the odds of having a vaccinated daughter compared to their counterparts. Promising areas for intervention include: targeted messaging about safety of the HPV vaccine, increasing parents'/caregivers' knowledge about the vaccine, and leveraging trusted messengers including health workers, faith leaders, and peer parents/caregivers.

Prophylactic HPV vaccines in patients with HPV-associated diseases and cancer

Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Prophylactic HPV vaccines have shown benefits in preventing subsequent HPV-related disease when administered before or soon after treatment. Based on our understanding of the HPV life cycle and vaccine mechanism of action, prophylactic HPV vaccination is not expected to clear active persistent HPV infection or unresected HPV-associated dysplastic tissue remaining after surgery. However, vaccination may reasonably be expected to prevent new HPV infections caused by a different HPV type as well as re-infection with the same HPV type, whether from a new exposure to an infected partner or through autoinoculation from an adjacent or distant productively infected site. In this review, we describe the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment and discuss potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines. We also consider how precise terminology relating to the use of prophylactic vaccines in this population is critical to avoid the incorrect implication that prophylactic vaccines have direct therapeutic potential, which would be counter to the vaccine's mechanism of action, as well as considered off-label. In other words, the observed effects occur through the known mechanism of action of prophylactic HPV vaccines, namely by preventing virus of the same or a different HPV type from infecting the patient after the procedure.

The challenge of identifying eligible girls for HPV vaccination: HPV mapping data verification in Malawi

Malawi introduced the human papillomavirus (HPV) vaccine nationwide in January 2019, with a target population of nine-year-old girls. Early in rollout, some health facilities reported stockouts, raising questions about the accuracy of the age eligibility of girls registered during the initial population mapping exercise. Mapping results showed that the estimated number of nine-year-old girls registered for vaccination was significantly higher than National Statistical Office (NSO) estimates, resulting in questions about enumeration of the target population. Consequently, the Ministry of Health of Malawi's Expanded Programme on Immunization (MOH-EPI) and immunization partners conducted a post-introduction data verification exercise to validate the eligibility of girls registered during mapping. Data were collected by immunization partners and representatives from national, zonal, and district levels. Dates of birth (DOB) were validated in HPV vaccine mapping registers and compared with information obtained from individual registered girls during school visits and their parents during home visits. HPV vaccine mapping registers were reviewed, showing that 76 percent of girls (n = 957) had DOBs within the vaccination eligibility range. A subset of the 957 girls (414) were interviewed; of them 74 percent (307) provided DOBs within the eligible period. Parents of the remaining eligible girls (543) were interviewed; 55 percent (297) of them, provided DOBs that were within the eligible period, indicating that, when using parents as an information source, 45 percent of the girls were outside the target age group. The eligibility verification exercise reviewed the accuracy of the mapping exercise and provided lessons for future target setting. Findings validate using NSO population estimates for target setting, incorporating the identification and registration of girls for HPV vaccination into RI microplanning headcounts, and verifying with parents the age and eligibility of girls registered before HPV vaccination is conducted.

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.

Benefit-risk assessment of HPV vaccination programs in Australia, the United States, and Japan

Human papillomavirus (HPV) vaccination is a global strategy for the prevention of cervical cancer (CC). Although Australia and the United States (US) have achieved high coverage, the cumulative HPV rate of the first vaccination for Japanese females born in 2008 was approximately 55%, despite policy efforts. This study compared the situation in Japan with that in Australia and the US, where vaccination rates are higher. We conducted a unified benefit-risk assessment using disability-adjusted life year (DALY) rates to quantify the expected net value (ENV) of HPV vaccination programs per 100,000 eligible girls in Australia (2013-2020), the US (2013-2020), and Japan (2013-2024). Data on vaccination coverage, adverse events (AEs), and CC incidence were sourced from national health agencies and the Global Burden of Disease Study 2019. The vaccination coverage was 78.3% in Australia, 50.1% in the US, and 21.4% in Japan during the survey period. The ENV gained were 52.9 for Australia, 56.7 for the US, and 23.4 for Japan, reflecting differences in vaccination rates and CC burden. Across countries, the reporting rate of AEs was <0.05%, with most reports related to nervous system disorders and nonspecific symptoms. The benefit-to-risk ratio in Japan improved 7.9-fold after the resumption of active vaccination recommendations in 2021, largely owing to reduced reports of AEs. Japan's lower ENV gained compared to those of Australia and the US is primarily attributable to its low vaccination coverage and higher DALY rate for CC. HPV vaccination programs in Australia and the US have demonstrated strong benefit-risk profiles. Achieving vaccination rates comparable to those in Australia and the US can substantially improve outcomes. Japan's recent policy changes and educational initiatives have reduced AE concerns; however, further efforts are needed to raise the coverage of international benchmarks.

Multiple cohort HPV vaccination in Zimbabwe: 2018–2019 program feasibility, awareness, and acceptability among health, education, and community stakeholders

Zimbabwe introduced human papillomavirus (HPV) vaccine nationally in May 2018, targeting multiple cohorts (girls aged 10-14 years) through a school-based vaccination campaign. One year later, the second dose was administered to the multiple cohorts concurrently with the first dose given to a new single cohort of girls in grade 5. We conducted cross-sectional surveys among health workers, school personnel, and community members to assess feasibility of implementation, training, social mobilization, and community acceptability. Thirty districts were selected proportional to the volume of the HPV vaccine doses delivered in 2018; two health facilities were randomly selected within each district. One health worker, school health coordinator, village health worker, and community leader were surveyed at each selected health facility and surrounding area during January-February 2020, using standard questionnaires. Descriptive analysis was completed across groups. There were 221 interviews completed. Over 60% of health workers reported having enough staff to carry out vaccination sessions in schools while maintaining routine vaccination services in health facilities. All school health coordinators felt the HPV vaccine should be delivered in schools in the future. Knowledge of the correct target cohort eligibility decreased from 91% in 2018 to 50% in 2020 among health workers. Understanding of HPV infection and use of HPV vaccine for cervical cancer prevention was above 90% for all respondents. Forty-two percent of respondents reported hearing rumors about the HPV vaccine, primarily regarding infertility and safety. Findings demonstrate the presence of highly knowledgeable staff at health facilities and schools, strong community acceptance, and a school-based HPV program considered feasible to implement in Zimbabwe. However, misunderstandings regarding target eligibility and rumors persist, which can impact vaccine uptake and coverage. Continued social mobilization efforts to maintain community demand and training on eligibility were recommended. Integration, partnerships, and resource mobilization are also needed to ensure program sustainability.

Human papillomavirus (HPV) vaccine introduction in Sikkim state: Best practices from the first statewide multiple-age cohort HPV vaccine introduction in India–2018–2019

Cervical cancer is a leading cause of cancer-associated mortality among women in India, with 96,922 new cases and 60,078 deaths each year, almost one-fifth of the global burden. In 2018, Sikkim state in India introduced human papillomavirus (HPV) vaccine for 9-13-year-old girls, primarily through school-based vaccination, targeting approximately 25,000 girls. We documented the program's decision-making and implementation processes. We conducted a post-introduction evaluation in 2019, concurrent with the second dose campaign, by interviewing key stakeholders (state, district, and local level), reviewing planning documents, and observing cold chain sites in two purposefully-sampled community areas in each of the four districts of Sikkim. Using standard questionnaires, we interviewed health and education officials, school personnel, health workers, community leaders, and age-eligible girls on program decision-making, planning, training, vaccine delivery, logistics, and communication. We conducted 279 interviews and 29 observations in eight community areas across four districts of Sikkim. Based on reported administrative data, Sikkim achieved >95% HPV vaccination coverage among targeted girls for both doses via two campaigns; no severe adverse events were reported. HPV vaccination was well accepted by all stakeholders; minimal refusal was reported. Factors identified for successful vaccine introduction included strong political commitment, statewide mandatory school enrollment, collaboration between health and education departments at all levels, and robust social mobilization strategies. Sikkim successfully introduced the HPV vaccine to multiple-age cohorts of girls via school-based vaccination, demonstrating a model that could be replicated in other regions in India or similar low- and middle-income country settings.

HPV vaccination coverage in three districts in Zimbabwe following national introduction of 0,12 month schedule among 10 to 14 year old girls

Zimbabwe has one of the highest incidence rates of cervical cancer in the world - 61.7 per 100,000 women. The government of Zimbabwe introduced bivalent HPV vaccine with a 0,12 month schedule to all 10-14 year old girls using a pulsed-campaign approach in May 2018 (dose 1) and May 2019 (dose 2). In August 2019, we conducted a population-based, two-stage cluster survey of households with girls who were eligible for the national HPV vaccination program to determine two-dose HPV vaccination coverage in three districts of Zimbabwe. All households with girls currently aged 11 to 15 years were line-listed through a census conducted in the pre-selected clusters from each district prior to survey administration. A simple random sample of eligible households was selected from these lists to estimate HPV vaccine coverage at sufficient power with a margin of error of +/- 5%. Criteria for district selection included estimated vaccine uptake (low, medium, high), rural/urban/peri-urban, geographic area, estimated number of girls not in school, and recent natural disasters or disease outbreaks. We oversampled households with girls aged 13 or 14 years at the time of dose 1. On-time dose 1 uptake ranged from 88 to 94% and two-dose HPV vaccine coverage ranged from 75 to 86% across the three districts. Nearly all vaccinations occurred in schools, and less than 2% of girls did not attend school. There were challenges assessing ages of girls at schools prior to vaccination - 9% of girls vaccinated were less than 10 years old at time of dose 1. Zimbabwe has demonstrated that high uptake and successful completion of 2-dose HPV vaccination can be achieved with an annual dosing schedule. Efforts going forward will need to focus on minimizing dropout between doses and routinizing annual vaccinations in schools for every subsequent new cohort of eligible girls in the country.

Tanzania’s human papillomavirus (HPV) vaccination program: Community awareness, feasibility, and acceptability of a national HPV vaccination program, 2019

In April 2018, Tanzania introduced the human papillomavirus (HPV) vaccine nationally to 14-year-old girls, utilizing routine delivery strategies (i.e. vaccinating girls at health facilities and community outreach, including schools). We sought to assess awareness, feasibility, and acceptability of the HPV vaccination program among health workers and community-level stakeholders. We conducted cross-sectional in-person surveys among health workers, school personnel, community leaders, and council leaders in 18 council areas across six regions of Tanzania in October-November 2019. Regions were purposively selected to provide demographic, geographic, and vaccination coverage variability; sub-regional levels used random or stratified random sampling. Surveys included questions on HPV vaccine training and knowledge, delivery strategy, target population, and vaccine and program acceptability. Descriptive analysis was completed for all variables stratified by respondent groups. Across the 18 councils, there were 461 respondents, including health workers (165), school personnel (135), community leaders (143), and council leaders (18). Over half of each respondent group (50-78%) attended a training or orientation on HPV vaccine. Almost 75% of the health workers and school personnel respondent groups, and less than half (45%) of community leaders correctly identified the target age group for HPV vaccine. Most (80%) of the health workers indicated HPV vaccination was available at health facilities and schools; most (79%) indicated that the majority of girls receive HPV vaccine in school. Approximately half (52%) of all respondents reported hearing misinformation about HPV vaccine, but 97% of all respondents indicated that HPV vaccine was either "very accepted" or "somewhat accepted" in their community. The HPV vaccination program in Tanzania was well accepted by community stakeholders in 18 councils; adequate knowledge of HPV vaccine and the HPV vaccination program was demonstrated by health workers and school personnel. However, continued technical support for integration of HPV vaccination as a routine immunization activity and reinforcement of basic knowledge about HPV vaccine in specific community groups is needed. The Tanzania experience provides an example of how this vaccine can be integrated into routine immunization delivery strategies and can be a useful resource for countries planning to introduce HPV vaccine as well as informing global partners on how to best support to countries in operationalizing their HPV vaccine introduction plans.

Impact of the human papillomavirus (HPV) vaccine supply shortage on Tanzania’s national HPV vaccine introduction

Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania

As part of the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls (DoRIS; NCT02834637), the current study is one of the first to evaluate the financial and economic costs of the national rollout of an HPV vaccination program in school-aged girls in sub-Saharan Africa and the potential costs associated with a single dose HPV vaccine program, given recent evidence suggesting that a single dose may be as efficacious as a two-dose regimen. The World Health Organization's (WHO) Cervical Cancer Prevention and Control Costing (C4P) micro-costing tool was used to estimate the total financial and economic costs of the national vaccination program from the perspective of the Tanzanian government. Cost data were collected in 2019 via surveys, workshops, and interviews with local stakeholders for vaccines and injection supplies, microplanning, training, sensitization, service delivery, supervision, and cold chain. The cost per two-dose and one-dose fully immunized girl (FIG) was calculated. The total financial and economic costs were US$10,117,455 and US$45,683,204, respectively, at a financial cost of $5.17 per two-dose FIG, and an economic cost of $23.34 per FIG. Vaccine and vaccine-related costs comprised the largest proportion of costs, followed by service delivery. In a one-dose scenario, the cost per FIG reduced to $2.51 (financial) and $12.18 (economic), with the largest reductions in vaccine and injection supply costs, and service delivery. The overall cost of Tanzania's HPV vaccination program was lower per vaccinee than costs estimated from previous demonstration projects in the region, especially in a single-dose scenario. Given the WHO Strategic Advisory Group of Experts on Immunization's recent recommendation to update dosing schedules to either one or two doses of the HPV vaccine, these data provide important baseline data for Tanzania and may serve as a guide for improving coverage going forward. The findings may also aid in the prioritization of funding for countries that have not yet added HPV vaccines to their routine immunizations.

High vaccine effectiveness persists for ten years after HPV16/18 vaccination among young Dutch women

The current study describes the long-term effectiveness of three-dose HPV16/18 vaccination among Dutch women who were eligible for vaccination during a catch-up campaign and were followed in an observational cohort study. Ten years post vaccination, vaccine effectiveness (VE) was estimated using generalized estimating equation models. VE against persistent infections with vaccine type infections (HPV16/18) was high at 95.8%. For cross protective type persistent infections (HPV31/33/45) this was 64.6%. There were no indications of waning of protection over time. This indicates solid long-term protection is provided by the vaccine and is promising with regard to the future clinical impact.

Improving access to human papillomavirus vaccines: A case study in the IA2030 core principle of partnership

Partnerships are fundamental to progress in immunization, and this is especially true for human papillomavirus (HPV) vaccination, which must be delivered in the context of a broader immunization, sexual and reproductive health, and cervical cancer prevention programs. Starting from the discovery and development of HPV vaccines, through to implementation and improvement of the program's resilience, partnerships have played a critical role. In May 2018, the Global Strategy to Accelerate the Elimination of Cervical Cancer set a target for 90 % of girls to be fully vaccinated with HPV vaccine by age 15 years. This will require effective partnership and multisectoral collaboration among current and future partners to ensure alignment of interests, efficient execution, and the establishment of mechanisms to resolve emerging challenges and pre-empt foreseeable risks. In ramping up this partnering approach, HPV can provide a template for other health and immunization programs.

Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20–45 years: A randomized, blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial

Human papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent). 1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20-26, 27-35, or 36-45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > -10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5. Among the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded -10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths. This study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.

HPV vaccine introduction and implementation in Low- and Middle-Income Countries

Cost of human papillomavirus vaccine delivery at district and health facility levels in Zimbabwe: A school-based vaccination program targeting multiple cohorts

After a pilot project in 2014-15 Zimbabwe introduced the human papillomavirus (HPV) vaccine nationally in 2018 for girls aged 10-14 years through a primarily school-based vaccination campaign with two doses administered at 12-month intervals. In 2019, a first dose was delivered to a new cohort of girls in grade 5 of girls age 10 years if out-of-school (OOS), along with a second dose to the 2018 multiple cohorts. Additional effort was made to identify and mobilize OOS girls by Village Health Workers (VHWs) in the community. Zimbabwe reported 1,569,905 doses of HPV vaccine administered during the 2018 and 2019 campaigns. This analysis evaluated the cost of Zimbabwe's national HPV vaccine introduction. A retrospective, incremental, ingredients-based cost analysis from the provider perspective was conducted in 2018 and 2019. Financial and economic cost data were collected at district and health facility levels using a two-stage cluster sampling approach and four cost dimensions: program activity, resource input, payer, and administrative level. Costs are presented in 2020 US$ in total and per dose. The total weighted costs for combined district and health facility administrative levels were US$ 828,731 (financial) and US$ 2,060,943 (economic). For service delivery, the total weighted cost per dose was US$ 0.16 (financial) and US$ 0.59 (economic). The program activities with the largest share of total weighted financial cost were training (37% of total) and service delivery (30%), while the largest shares of total weighted economic costs were service delivery (45%) and training (19%). Efforts by VHWs to reach OOS girls resulted in an additional US$ 2.99 in financial cost per dose and US$ 7.79 in economic cost per dose. The service delivery cost per dose was lower than that documented in the pilot program cost analysis in Zimbabwe and studies elsewhere, reflecting a campaign delivery approach that spread fixed costs over a large vaccination cohort. The additional cost of reaching OOS girls with the HPV vaccine was documented for the first time in low- and middle-income countries, which may provide information on potential costs for other countries.

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination regimen in a high-income country setting: An analysis in the United Kingdom

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13-14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was < 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.

Long-term effectiveness of human papillomavirus vaccines among adult women: A real-world scenario

This study aimed to determine the real-world effectiveness of bi- or quadrivalent human papillomavirus (HPV) vaccines in Thai adult women ≥5 years post-vaccination in reducing HPV 16/18-associated low-grade squamous intraepithelial lesions or worse (LSIL+), atypical squamous cells of undetermined significance or worse (ASC-US+), and HPV 16/18 positivity. A retrospective cohort study was conducted among Thai women aged 20-45 years in Bangkok. The vaccinated and unvaccinated groups were matched according to baseline years. HPV/Pap test results were collected from the medical records and/or obtained by cervical sample collection at the study sites. Adjusted hazard ratios were measured using multivariable Cox regression analyses. A total of 993 participants (493 vaccinated and 500 unvaccinated) were enrolled from 2018 to 2019. The median ages at baseline of the vaccinated and unvaccinated groups were 33 years (interquartile range [IQR] 27-38) and 34 years (IQR 30-38), respectively. The median follow-up periods were 7.3 years (IQR 6.1-8.6) and 7.2 years (IQR 5.8-8.9) for the vaccinated group and the unvaccinated group, respectively. More women in the vaccinated group were single (29.2% vs. 13.2%, P 20,000 THB/month, 63.9% vs. 62.4%, respectively, P = 0.685). There were no cases of HPV 16/18-associated LSIL+ in the vaccinated group, whereas there were four cases in the unvaccinated group. HPV vaccine effectiveness was 88.0% (95% CI 2.0-98.5) in the reduction of HPV 16/18-associated ASC-US+, and 84.6% (95% CI 43.5-95.8) in the reduction of HPV 16/18 positivity. HPV vaccine effectiveness was high in adult women in a real-world scenario in a developing country. Free HPV vaccination in adult women in this age group should be further explored when vaccine supplies are not limited. (HPV: human papillomavirus. LSIL+: low-grade squamous intraepithelial lesion or worse. ASC-US+: atypical squamous cells of undetermined significance or worse).

In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer

Somatic mutation-derived neoantigens are associated with patient survival in breast and ovarian cancer. These neoantigens are targets for cancer, as shown by the implementation of neoepitope peptides as cancer vaccines. The success of cost-effective multi-epitope mRNA vaccines against SARS-Cov-2 in the pandemic established a model for reverse vaccinology. In this study, we aimed to develop an in silico pipeline designing an mRNA vaccine of the CA-125 neoantigen against breast and ovarian cancer, respectively. Using immuno-bioinformatics tools, we predicted cytotoxic CD8

Acceptability of vaccination against human papillomavirus among women aged 20 to 45 in rural Hunan Province, China: A cross-sectional study

This study aimed to examine the intentions of and barriers to vaccination against human papillomavirus (HPV) among women aged 20 to 45 in rural areas, and to determine the popular sources to getting information about HPV vaccine and vaccination. This cross-sectional study was conducted in 2018 with a sample of women aged 20 to 45 from rural areas of Hunan Province in China. Anonymous self-administered questionnaires were used to collect sociodemographic information and characteristics related to reproductive health of participants, and intentions of and barriers to HPV vaccination. All statistical analysis methods were performed with SPSS 18.0. A total of 2101 women participated in the study, with 58.55% intended to vaccinate against HPV. Increased intention of HPV vaccination was associated with higher age (adjusted odds ratio [AOR] = 1.35 and 1.50, respectively) and education level (AOR = 1.13 and 1.47, respectively). Women who have heard of HPV vaccine (AOR = 2.67, 95% confidence interval [CI]: 1.20-5.98) and have been aware of that cervical cancer could be prevented (AOR = 2.01, 95%CI: 1.44-2.82) were more willing to vaccinate. Having never heard of HPV vaccine and worry about efficacy and safety of vaccines were the most commonly cited reasons to refuse vaccination. The preferred source to get the knowledge was medical personnel (58.45%), followed by WeChat or Microblog, TV programs, and Internet. We found the intention of HPV vaccination among women aged 20 to 45 in rural China is low. Findings highlighted the importance of knowledge and trust in HPV vaccine, and suggested strengthening educational interventions on HPV vaccine and vaccination through multiple sources, including HPV vaccine coverage in health insurance to increase access.

Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries

There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

The impact of over ten years of HPV vaccination in England: Surveillance of type-specific HPV in young sexually active females

The UK national human papillomavirus (HPV) vaccination programme was introduced in 2008 using the bivalent HPV16/18 vaccine, changing to the quadrivalent HPV6/11/16/18 vaccine from 2012. We provide an analysis of type-specific HPV prevalence in young sexually active females in England to end 2020 (when the first routinely HPV vaccinated females were reaching 25 years of age and entering the National Health Service Cervical Screening Programme), showing the impact of over ten years of high coverage HPV vaccination. Residual vulvovaginal swabs (VVS) were collected from 16 to 24 year old women attending for chlamydia screening between 2010 and 2020, anonymised and tested for type-specific HPV DNA. Trends in vaccine and non-vaccine HPV type prevalence were compared over time and association with vaccination coverage was evaluated within the post-vaccination period. A total of 21,168 eligible VVS specimens were tested for HPV DNA. The prevalence of HPV16/18 in sexually active 16-18 year old females who were offered vaccination aged 12-13 years was <1% in the most recent years tested, compared to over 15% prior to the vaccination programme in 2008. The magnitude of these decreases also suggests reduced transmission is offering some herd protection to unvaccinated females. HPV31/33/45 prevalence also steadily decreased, providing evidence of cross-protection. HPV6/11 prevalence remained stable during the bivalent vaccine period, with more recent declines, as expected due to the use of the quadrivalent vaccine. There has been no substantive increase in the prevalence of other high-risk (HR) HPV types. More than ten years of high coverage HPV vaccination in adolescent females in England has delivered dramatic declines in the prevalence of HPV vaccine-types and closely related HPV types in females in the vaccine eligible age group, and no indication of type replacement. These findings should enable confidence in planning for cervical screening of these females, and in predicting declines in HPV-related cancers.

A nationwide post-marketing survey of knowledge, attitude and practice toward human papillomavirus vaccine in general population: Implications for vaccine roll-out in mainland China

Human papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China. Participants aged 18-45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics. 4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines. Findings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.

How acceptable is adolescent self-consent for the HPV vaccination: Findings from a qualitative study in south-west England

Human Papillomavirus (HPV) vaccination programmes have the potential to reduce the incidence of cervical cancer. The preferred age for HPV vaccination is 12-13 years for optimal benefit. The legal framework in England allows adolescents to be vaccinated without parental consent if they are assessed as competent. A 'South West Template Pathway on Self Consent for School Aged Immunisations' was developed to improve uptake of immunisations in south-west England. To examine how acceptable the new procedures are to the young women, parents and carers, school staff and immunisation nurses involved. The research was undertaken in two local authorities in south-west England during the 2017/18 and 2018/19 programme years. Semi-structured digitally recorded interviews were undertaken with 53 participants: one health service manager, three immunisation nurses, five staff at alternative education providers, three staff at mainstream schools, 19 young women and 22 parents. All recordings were transcribed verbatim and thematic analysis was undertaken, assisted by NVivo software. Most participants were not fully aware of the legal framework that enables a young person to self-consent to vaccination. There was a strong presumption that parents should make decisions affecting the health of their children. The preferred age at which the HPV vaccination is administered (12-13 years) contributed to reluctance in endorsing self-consent which was thought to have the potential to break down trust between parents and school staff, and within families. In practice, formal self-consent was rare. Unresolved issues in relation to adolescent self-consent include public and professional perceptions of young people's rights and abilities to take responsibility for decisions affecting their health, and concerns about the impact of self-consent on relationships both within families and between professionals and the families they serve.

HPV cervical infections and serological status in vaccinated and unvaccinated women

Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.

Parent, provider and vaccinee preferences for HPV vaccination: A systematic review of discrete choice experiments

To systematically review, appraise and evaluate available evidence regarding discrete-choice experiments (DCEs) for the human papilloma virus (HPV) vaccination in order to support policymakers in making reasonable and effective vaccination program implementation decisions. A systematic literature review was conducted using the databases PubMed and Embase for DCEs in HPV up to May 2019. Extracted data was tabulated and two checklists were used for the quality appraisal of the included studies. All attributes were categorized in outcome, process or costs attributes and the relative importance of attributes was calculated using the range method. Out of 164 identified studies, 12 met the inclusion criteria. Eight were from high income countries (HICs) and four from low and middle-income countries (LMICs). Five studies each examined vaccinee and parent preferences, while only two assessed the providers' preferences. The studies were rather heterogenous in terms of the populations investigated, the attributes included and the methodologic approach. Overall, outcome measures were the most prominent attributes and effectiveness consistently yielded high relative importance scores. But also process factors, such as the age at vaccination, played an important role for decision making. Discrepancies between HICs and LMICs were most prominent for cost attributes. The heterogenous preferences this review elicited highlight the importance of context when making decisions grounded on consumer preferences. Especially the lack of evidence from LMICs, where the burden of cervical cancer is highest, is worrisome. In order to increase uptake, close vaccination gaps and reduce current inequities in (reproductive) healthcare, policy makers need to understand the features that drive individual vaccination decisions and adapt national and clinical guidelines accordingly. Future research therefore needs to focus on LMICs in order to elicit preferences of those most vulnerable populations.

HPV vaccine uptake among daughters of Latinx immigrant mothers: Findings from a cluster randomized controlled trial of a community-based, culturally relevant intervention

We examined the efficacy of a culturally relevant, community-based HPV vaccination intervention among Latinx immigrant mothers with daughters aged 9-12 in Alabama. We conducted a cluster-randomized controlled trial with "place of residence" (e.g., apartment complexes, trailer parks) as the unit of randomization that evaluated two interventions: 1) promotion of HPV vaccination and 2) promotion of healthy eating and appropriate nutrition label interpretation. Identical baseline/post/7-month follow up questionnaires were completed by all participants and both interventions consisted of four group sessions and one individual session. A total of 40 locations were randomized with 317 mother-daughter dyads enrolled in the study between May 2013 and October 2017. A total of 278 mother-daughter dyads met full eligibility and initiated the intervention/control participation. Retention rate overall was 93.2% (92.6% for the intervention arm and 93.7% for the control arm). Daughters in the intervention arm were significantly more likely to receive one, two, and three doses of HPV vaccine than daughters in the control arm p < 0.001). In multivariate analyses, mothers in the intervention arm had a six times greater odds of vaccinating daughters with the first dose (OR = 5.96, 95% CI: 3.38, 10.49), eight times greater odds of vaccinating daughters with the second dose (OR = 8.09, 95% CI: 4.0, 16.35), and more than 16 times greater odds of completing the three-dose HPV vaccine series than mothers in the control arm after adjusting for mother's age, time in the U.S., income, and daughter's health insurance status (OR = 16.5, 95% CI: 5.73, 47.48). Only perceived risk of their daughters' future HPV infection remained significant as a predictor of three-dose HPV vaccination completion (OR = 0.69, 95% CI: 0.23, 2.1). A theory-driven, culturally-relevant intervention developed through extensive formative assessments in collaboration with community members can effectively promote HPV vaccination among 9-12 years of age daughters of Latina immigrants.

Strategic health communication on social media: Insights from a Danish social media campaign to address HPV vaccination hesitancy

To evaluate whether the social media strategy developed for the campaign Stop HPV - stop cervical cancer was successful at engaging target groups in communication regarding HPV vaccination. In 2009, the Human Papillomavirus (HPV) vaccine became part of the Danish childhood vaccination program to protect Danish girls from cervical cancer. In 2015, after a period of massive media coverage questioning the safety of the HPV vaccination, a rapid decline in HPV vaccination coverage was observed. An information campaign was therefore launched in May 2017 to address HPV vaccination hesitancy. THE SOCIAL MEDIA STRATEGY: 'Heart-brain communication' combined facts and emotions through varied content. Community management guidelines were worked out to ensure that there was positive dialogue. Key Point Indicators (KPI) for Engagement Rate (ER) and Click Through Rate (CTR) were chosen to uphold engagement and traffic from Facebook to the website. The KPIs were used to measure effectiveness. In January 2019, the social media campaign had reached 8,020,000 people with an average of 127 comments per post. The average ER from May 2017 to halfway through 2018 was 6.07% and the CTR was 2.09%. The content subgroup personal stories was the most effective in creating positive dialogue. One year after the launch of the campaign, the number of positive comments had increased from less than 50% to approximately 75%. A comprehensive social media strategy using 'heart-brain communication' proved useful in a campaign for HPV vaccination. The success of the social media strategy was due to meticulous planning prior to launching the campaign, the use of content subgroups, the allocation of adequate resources for community management, the empirical analysis of content, and the use of evaluation results as guidance for the production of new content.

Potential health impact and cost-effectiveness of bivalent human papillomavirus (HPV) vaccination in Afghanistan

Human papillomavirus (HPV) vaccination has not been introduced in many countries in South-Central Asia, including Afghanistan, despite the sub-region having the highest incidence rate of cervical cancer in Asia. This study estimates the potential health impact and cost-effectiveness of HPV vaccination in Afghanistan to inform national decision-making. An Excel-based static cohort model was used to estimate the lifetime costs and health outcomes of vaccinating a single cohort of 9-year-old girls in the year 2018 with the bivalent HPV vaccine, compared to no vaccination. We also explored a scenario with a catch-up campaign for girls aged 10-14 years. Input parameters were based on local sources, published literature, or assumptions when no data was available. The primary outcome measure was the discounted cost per disability-adjusted life-year (DALY) averted, evaluated from both government and societal perspectives. Vaccinating a single cohort of 9-year-old girls against HPV in Afghanistan could avert 1718 cervical cancer cases, 125 hospitalizations, and 1612 deaths over the lifetime of the cohort. The incremental cost-effectiveness ratio was US$426 per DALY averted from the government perspective and US$400 per DALY averted from the societal perspective. The estimated annual cost of the HPV vaccination program (US$3,343,311) represents approximately 3.53% of the country's total immunization budget for 2018 or 0.13% of total health expenditures. In Afghanistan, HPV vaccine introduction targeting a single cohort is potentially cost-effective (0.7 times the GDP per capita of $586) from both the government and societal perspective with additional health benefits generated by a catch-up campaign, depending on the government's willingness to pay for the projected health outcomes.

Human papillomavirus (HPV) vaccination in the transition between adolescence and adulthood

Young adulthood is characterized by changes in health care decision-making, insurance coverage, and sexual risk. Although the human papillomavirus (HPV) vaccine is now approved for adults up to age 45, and catch-up vaccination is currently recommended up through age 26, vaccination rates remain low in young adults. This study explored perspectives on HPV vaccination among young adults receiving care at the student health center of a large public university. We conducted semi-structured interviews (n = 27) and four focus groups with female and male undergraduate and graduate students (n = 18) and semi-structured interviews with health care providers (n = 6). Interviews and focus groups explored perceived risk of HPV infection, benefits of the HPV vaccine, and motivations for and barriers to HPV vaccination. Many young adults cited their parents' views and recommendations from medical providers as influential on their decision-making process. Students perceived that cervical cancer prevention was a main benefit of the HPV vaccine and sexual activity was a risk factor for HPV infection. Students often lacked knowledge about the vaccine's benefits for males and expressed some concerns about the safety and side effects of a vaccine perceived as new. Logistical barriers to vaccination included uncertainty over vaccination status and insurance coverage for the vaccine, and concerns about balancing the vaccine schedule with school obligations. Providers' vaccine recommendations were impacted by health system factors, including clinical infrastructure, processes for recommending and documenting vaccination, and office visit priorities. Suggested vaccination promotion strategies included improving the timing and messaging of outreach efforts on campus and bolstering clinical infrastructure. Although college may be an opportune time to reach young adults for HPV vaccination, obstacles including navigating parental influence and independent decision-making, lack of awareness of vaccination status, and numerous logistical and system-level barriers may impede vaccination during this time.

HPV vaccination intent and willingness to pay for 2-,4-, and 9-valent HPV vaccines: A study of adult women aged 27–45 years in China

This study aims to investigate acceptance and willingness to pay for HPV vaccination among adult women in China. An online survey was sent to mothers aged 27-45 years of primary school pupils in the Fujian province, China. Participants completed questions about HPV related knowledge and health beliefs, intention to take the HPV vaccine and the willingness to pay for bivalent vaccine (2vHPV), quadrivalent vaccine (4vHPV), and 9-valent HPV vaccine (9vHPV). Of a total of 2339 complete responses, 58.3% reported intent to obtain HPV vaccine. Mothers who were younger in age, residing in urban, working in managerial or professional occupations, who knew someone with cervical cancer and who were able to make independent decisions about the HPV vaccine (vs. joint decision with spouse) were more likely to express intent to have HPV vaccination. Perceived barriers, cues to action and self-efficacy were three of the constructs in the health belief model that significantly influenced HPV vaccination intent. A higher proportion of participants expressed willingness to pay for 2vHPV (81.2%) and 4vHPV (75.9%), as compared to 9vHPV (67.7%). Adults women expressed moderate intention to receive the HPV vaccine. Intervention to address barriers to uptake of the HPV vaccine among adult women in China is warranted.

Awareness and knowledge of HPV and HPV vaccination among adults ages 27–45 years

Recent guidelines indicate adults 27-45 years old can receive the human papillomavirus (HPV) vaccine based on a shared-decision with their healthcare provider. With this expansion in recommendations, there is a need to examine the awareness and knowledge of HPV and HPV vaccination among this age group for cancer prevention. HINTS-5 Cycle-2 is a national survey of US adults, and was restricted to a complete case analysis of adults ages 27-45 years (N = 725). Sociodemographic, healthcare, and health information correlates were assessed for the outcomes of HPV awareness, HPV vaccine awareness, knowledge of HPV and cervical cancer, and knowledge of HPV and non-cervical cancers. Survey-weighted logistic regression models were conducted. Most respondents were aware of HPV (72.9%) and HPV vaccination (67.1%). Respondents were more likely to be aware of HPV and HPV vaccination if they were female, had a higher level of education, and had previous cancer information seeking behaviors. Although there was widespread knowledge of HPV as a cause of cervical cancer (79.6%), knowledge of HPV as a cause of non-cervical cancers was reported by a minority of respondents (36.1%). College education was positively associated with cervical cancer knowledge (aOR = 4.62; 95%CI: 1.81-11.78); however, no significant correlates were identified for non-cervical HPV associated cancer knowledge. While more than half of adults ages 27-45 years are aware of HPV and HPV vaccination, there are opportunities to improve awareness and knowledge, particularly related to non-cervical cancers, as these are critical first steps toward shared decision-making for HPV vaccination in mid-adulthood.

Prevalence of human papillomavirus (HPV)-vaccine types by race/ethnicity and sociodemographic factors in women with high-grade cervical intraepithelial neoplasia (CIN2/3/AIS), Alameda County, California, United States

We evaluated racial/ethnic differences in prevalence of oncogenic HPV types targeted by the quadrivalent HPV vaccine (16/18) and nonavalent HPV vaccine (31/33/45/52/58) in women diagnosed with CIN2/3/AIS after quadrivalent HPV vaccine introduction (2008-2015). Typing data from 1810 cervical tissue specimen from HPV-IMPACT (Alameda County, California, US), a population-based CIN2/3/AIS surveillance effort, were analyzed. Using log-binomial regression, we calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) comparing type prevalence by race/ethnicity, adjusted for health insurance, age, CIN2/3/AIS grade, and time period, overall and in the "early vaccine era" (2008-2011) and "later vaccine era" (2012-2015). Overall, oncogenic HPV16/18 prevalence was significantly lower among black (43%) and Hispanic (43%) women compared with white (52%) women (aPR (95% CI): 0.80 (0.70, 0.93) and 0.80 (0.70, 0.91), respectively). In 2008-2011, proportion of HPV16/18 detected was significantly lower in black (47%), Hispanic (46%), and Asian (42%) women compared to white (58%) women (aPR (95% CI): 0.80 (0.67, 0.96), 0.75 (0.63, 0.90), and 0.73 (0.58, 0.90), respectively). There were no significant differences in 2012-2015. Between the two eras, HPV16/18 prevalence declined in white (-11%), black (-9%), and Hispanic (-6%) women, and increased in Asian women (12%). Decreasing HPV 16/18 prevalence in CIN2/3/AIS lesions in white, black, and Hispanic women may suggest benefit from quadrivalent vaccination. In our unadjusted analysis of HPV31/33/45/52/58, prevalence did not differ significantly by race/ethnicity, but was significantly higher among Hispanic women (32%) compared to white women (27%) after adjustment (aPR (95%CI): 1.22 (1.02, 1.47). Prevalence was also non-significantly higher among black (32%) and Asian (33%) women. This analysis suggests that the nonavalent vaccine's potential for impact against cervical precancers will not be lower in women of color compared to white women. These data underscore the importance of equitable vaccination in facilitating continued declines of vaccine-preventable HPV types among all women.

Impact of reduced human papillomavirus vaccination coverage rates due to COVID-19 in the United States: A model based analysis

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected utilization of preventative health care, including vaccines. We aimed to assess HPV vaccination rates during the pandemic, and conduct a simulation model-based analysis to estimate the impact of current coverage and future pandemic recovery scenarios on disease outcomes. The model population included females and males of all ages in the US. The model compares pre-COVID vaccine uptake to 3 reduced coverage scenarios with varying recovery speed. Vaccine coverage was obtained from Truven Marketscan™. Substantially reduced coverage between March-August 2020 was observed compared to 2018-2019. The model predicted that 130,853 to 213,926 additional cases of genital warts; 22,503 to 48,157 cases of CIN1; 48,682 to 110,192 cases of CIN2/3; and 2,882 to 6,487 cases of cervical cancer will occur over the next 100 years, compared to status quo. Providers should plan efforts to recover HPV vaccination and minimize potential long-term consequences.

Promoting adolescent health through integrated human papillomavirus vaccination programs: The experience of Togo

The introduction of the Human papillomavirus (HPV) vaccine has shown potential to not only prevent cervical cancer but also drive adolescents' access to other health care services, even in low-income countries. Few studies have been conducted to date to identify best practices and estimate the acceptance, operational challenges and benefits of including broader adolescent health interventions into immunization efforts, knowledge which is essential to supporting widespread integration. In this paper we review the efforts undertaken by the government of Togo to integrate adolescent health programming with the HPV vaccination roll out. With the support of partners (GAVI, WHO, UNFPA and UNICEF), the country successfully completed, in 2017, two years of an HPV vaccine demonstration project, which entailed vaccinating 10-year-old girls against HPV in two selected districts of the country and integrating a health education component focused on puberty education / menstrual hygiene and hand washing practice. Our study is a post-implementation program evaluation, using mixed methods to assess key questions of feasibility and acceptability of an integrated adolescent package of care. It showed that the HPV vaccination in conjunction with the health education sessions was well received by the majority of health care providers, teachers and parents. Our study confirmed that in Togo it proved feasible to combine education and HPV vaccination in school-based service delivery. However, more operational research is neded to understand how to increase the impact and sustainability of the co-delivery of interventions. We did not analyze the health impact and cost implications of the intervention, which will be an important consideration for scaling up such integration efforts alongside routine immunization.

The projected cost-effectiveness and budget impact of HPV vaccine introduction in Ghana

Cervical cancer is responsible for around one-quarter of all cancer deaths among Ghanaian women. Between 2013 and 2015, Ghana conducted a pilot of HPV vaccination among 10-14-year-old girls in four regions; however, the country has yet to introduce the vaccine nationally. This study projected the cost-effectiveness and budget impact of adding HPV vaccination into Ghana's national immunization program. We used a proportional outcomes model (UNIVAC, version 1.4) to evaluate the cost-effectiveness of introduction with bivalent (Cervarix™) and quadrivalent (Gardasil®) vaccines from government and societal perspectives. Vaccine introduction was modeled to start in 2022 and continue over ten birth cohorts using a combined delivery strategy of school (80%) and community outreach (20%). We modeled vaccination in a single age cohort of 9-year-old girls vs. a multi-age cohort of 9-year-old girls (routine) and 10-14-year-old girls (one-time campaign) compared to no vaccination. Health outcomes included cervical cancer cases, hospitalizations, deaths, and disability-adjusted life years (DALYs). We applied a discount rate of 3% to costs and outcomes. All monetary units are reported in USD 2018. National HPV vaccination in Ghana was projected to be cost-effective compared to no vaccination in all scenarios evaluated. The most cost-effective and dominant strategy was vaccination among 9-year-old girls, plus a one-time campaign among 10-14-year-old with the bivalent vaccine ($158/DALY averted from the government perspective; 95% credible range: $19-$280/DALY averted). Projected average annual costs of the vaccine program ranged from $11.2 to $15.4 M, depending on strategy. This represents 11-15% of the estimated total immunization costs for 2022 ($100,857,875 based on Ghana's comprehensive Multi-Year Plan for Immunization, 2020-2024). Our model suggests that introducing HPV vaccination would be cost-effective in Ghana under any strategy when willingness-to-pay is at least 40% GDP per capita ($881). Inclusion of a one-time catch-up campaign is shown to create greater value for money than routine immunization alone but would incur greater program costs.

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis

National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.

Integration of other services with human papillomavirus vaccination; lessons from earlier in the life course highlight the need for new policy and implementation evidence

Integration of vaccination against human papillomavirus (HPV) with other essential health services for adolescents has been proposed in global strategies and tested in demonstration projects in low- and middle-income countries (LMIC). Published experiences, global guidance, and one key example, the implementation of "HPV Plus" in Tanzania, all demonstrate the need for greater operational evidence to guide future implementation and policy. Review of experiences earlier in the life course, integrating post-partum family planning with infant immunization, show lessons from 13 LMICs that can apply to provision of adolescent health information and services alongside HPV vaccination. Three distinct models of integration emerge from this review comprising: 1) multiple tasks and functions by health staff providing vaccination and other care, or 2) secondary tasks added to the main function of vaccination, or 3) co-location of matched services provided by different staff. These models, with strengths and weaknesses demonstrated in family planning and immunization experiences, apply in different ways to the three main platforms used for HPV vaccination: school, facility or community. For HPV vaccination policy and programming, an initial need is to combine the existing evidence on vaccine service delivery - including coverage, efficiency, cost, and cost-effectiveness information - with what is known on how integration works in practice; the operational detail and models employed. This synthesis may enable assessment which models best suit the different service delivery platforms. An additional need is to link this with more tailored local assessments of the adolescent burden of disease and other determinants of their well-being to develop new thinking on what can and cannot be done to integrate other services alongside HPV vaccination. New approaches placing adolescents at the center are needed to design services tailored to their preferences and needs. The potential synergies with cervical cancer screening and treatment for older generations of women, also require further exploration. Coordinated action aligning HPV vaccination with broader adolescent health and wellbeing will generate social, economic and demographic benefits, which in themselves are sufficient justification to devote more attention to integrated approaches.