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 >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.

Feasibility and acceptability of telehealth and contactless delivery of human papillomavirus (HPV) self-testing for cervical screening with Maori and Pacific women in a COVID-19 outbreak in Aotearoa New Zealand.

AIM: To determine the feasibility and acceptability of a telehealth offer and contactless delivery of human papillomavirus (HPV) cervical screening self-test during the 2021 COVID-19 Level 4 lockdown in Auckland, New Zealand. METHODS: A small proof-of-concept study was undertaken to test telehealth approaches in never-screened, due or overdue Maori and Pacific women enrolled in a local Primary Health Organisation (PHO). Study invitation, active follow-up, nurse-led discussions, result notification and a post-test questionnaire were all delivered through telehealth. RESULTS: A sample of 197 eligible Maori and Pacific women were invited to take part, of which 86 women were successfully contacted. Sixty-six agreed to take part. Overall uptake was 61 samples returned (31.8%) and uptake of all contactable women was 70.9%. Six of the 61 HPV self-tests (9.8%) were positive, all for non 16/18 types, and were referred for cytology. Three had negative cytology results, and three with positive cytology results were referred for colposcopy. CONCLUSION: The offer of HPV self-testing during COVID-19 lockdown was both feasible and highly acceptable for Maori and Pacific women. Importantly, HPV self-testing via telehealth and mail-out, alongside other options, offers a potential pro-equity approach for addressing the impact of deferred screens due to COVID-19 and other longstanding coverage issues.

Scientific evaluation of alleged findings in HPV vaccines: Molecular mimicry and mouse models of vaccine-induced disease.

Cervical cancer is caused by infections of the human papillomavirus (HPV), which can be prevented by vaccinations. In Japan, although about 3000 people die of cervical cancer annually, the HPV vaccination rate has remained extremely low in the eligible population since many Japanese have been concerned that "diverse symptoms," such as chronic pain, movement disorders, and cognitive impairment, may occur as adverse reactions after HPV vaccination. The concern has been raised by media coverage of the ongoing HPV vaccine lawsuits, in which the plaintiffs complained of their symptoms caused by HPV vaccination. The claims have been based on the alleged pathogenic findings in research articles on HPV vaccines, summarized in the document prepared by the plaintiffs' attorneys. We critically evaluated these articles, in which the authors proposed the following findings/hypothesis: (i) molecular mimicry between HPV L1 and human proteins leads to the production of cross-reactive antibodies; and (ii) HPV vaccine injection in mice causes damage in the brain, a mouse model for HPV vaccine associated neuro-immunopathic syndrome (HANS). We found that these hypotheses were based mainly on the findings from a few research groups and that all the articles had flaws in the method, result, or discussion sections. Our current evaluation should help better understand the validity of the findings, which have been often misunderstood as the truth by the general public. We propose to accumulate high-quality data on potential adverse events following HPV vaccination and to continue critically evaluating them.

Harnessing Human Papillomavirus' Natural Tropism to Target Tumors.

Human papillomaviruses (HPV) are small non-enveloped DNA tumor viruses established as the primary etiological agent for the development of cervical cancer. Decades of research have elucidated HPV's primary attachment factor to be heparan sulfate proteoglycans (HSPG). Importantly, wounding and exposure of the epithelial basement membrane was found to be pivotal for efficient attachment and infection of HPV in vivo. Sulfation patterns on HSPG's become modified at the site of wounds as they serve an important role promoting tissue healing, cell proliferation and neovascularization and it is these modifications recognized by HPV. Analogous HSPG modification patterns can be found on tumor cells as they too require the aforementioned processes to grow and metastasize. Although targeting tumor associated HSPG is not a novel concept, the use of HPV to target and treat tumors has only been realized in recent years. The work herein describes how decades of basic HPV research has culminated in the rational design of an HPV-based virus-like infrared light activated dye conjugate for the treatment of choroidal melanoma.

Screening for High-Risk Human Papillomavirus Using Passive, Self-Collected Menstrual Blood.

OBJECTIVE: To assess concordance and acceptability of a modified menstrual pad compared with a clinician-collected high-risk human papillomavirus (HPV) sample. METHODS: This was a prospective observational study. Women presenting for either cervical cancer screening or with a history of high-risk HPV positivity were eligible. Three samples were requested from participants: 1) clinician-collected cervical specimens; 2) self-collected vaginal swabs; and 3) a modified menstrual pad, which was taken home for use during the next menstruation. All samples were processed using the Cobas HPV test. Menstrual pad dried blood spots were eluted, then similarly processed. RESULTS: Of 153 women enrolled in the study, 106 provided menstrual pad samples and clinician-collected cervical specimens for high-risk HPV analysis. For samples in which the interval between the clinician-collected specimen and the menstrual pad sample was less than 2 months, the concordance was 94% (95% CI 83-98). For women who tested positive for high-risk HPV who presented for general screening and those with more than cervical intraepithelial neoplasia 2, menstrual pad and clinician-collected specimen agreement was 100% (95% CI 32.5-100). Among participants, 22.9% expressed discomfort with the self-collected vaginal swabs and opted out of collection. Overall, 94.0% of participants preferred the menstrual pad over clinician-collected sampling. Twelve patients were found to be positive for HPV on the menstrual pad sample but negative on the clinician-collected specimen. CONCLUSION: Among women who tested positive for HPV, the menstrual pad showed highly concordant results compared with clinician-collected sampling. This collection approach shows promise for integration into cervical cancer prevention programs.

Challenges and lessons from a school-based human papillomavirus (HPV) vaccination program for adolescent girls in a rural Nigerian community.

BACKGROUND: Over 80% of new cervical cancer cases occur in women living in low- and middle-income countries. It is the second highest cause of female cancer deaths in Nigeria. School based vaccination programs are an effective strategy for delivering the HPV vaccine to adolescent girls. This study aims to understand the challenges to implementing school-based HPV vaccination programs, particularly in a remote rural setting where vaccine hesitancy is high. METHODS: A 22- item interviewer administered questionnaire was used to evaluate HPV knowledge and willingness to get the HPV vaccinate among 100 female secondary school students as part of an HPV vaccination pilot in a rural community in Kebbi State, Nigeria. Additionally, semi-structured interviews were used to assess community knowledge and attitudes on cervical cancer and HPV vaccination. Data collected were analyzed thematically to understand challenges and generate lessons for vaccine delivery in the study setting. RESULTS: Knowledge of HPV and cervical cancer among junior secondary school aged girls was fair with a mean score of 66.05%. For senior secondary school aged girls, the knowledge score ranged from 70 to 100% with a mean of 96.25% indicating good knowledge of HPV and cervical cancer. All participants (n = 100) received the first vaccine dose but due to COVID-19, 33 participants were not able to complete the vaccine dosage within the recommended 6-month schedule. Of the parents who provided consent, none could afford the vaccine out of pocket. Challenges to vaccine delivery included operational costs exacerbated by lack of adequate health workforce and infrastructure in the study setting. CONCLUSION: An exploration of sociocultural perspectives and contextual realities is crucial to understanding the complexities of HPV vaccine introduction from the perspective of the target audience, and the local community. Strategies for introducing the HPV vaccine should address community concerns through effective communication, appropriate delivery, and targeted advocacy to make the vaccination program locally relevant. While school-based HPV immunization programs have been shown to be successful, adequate design, planning and monitoring is important. Additionally, considerations must be made to account for the high operational cost of vaccine delivery in rural, hard to reach areas where human resources and infrastructure are limited.

Online educational program for parents of adolescents on human papillomavirus vaccination during COVID pandemic: A feasibility check.

Background: Human papillomavirus (HPV) vaccination for adolescents helps in the prevention of preventable cancers caused due to HPV infection. However, many adolescents are not vaccinated due to lack of knowledge among parents. Objective: This study aimed to compare the level of knowledge and attitude of parents on HPV vaccination before and after the online educational intervention. Methods: Across-sectional pilot study was conducted among a sample of 45 parents of adolescents studying in class 7th-9th. The parents were selected two-stage simple random sampling and assigned randomly to three groups with three different methods of education - online lecture with PowerPoint presentation, online short film with discussion, and self-learning online booklet. Pre- and postintervention knowledge was assessed with a structured questionnaire and attitude with modified Likert scale administered online. Wilcoxon and Kruskal-Wallis tests were used to find the statistical significance in the study. Results: Only 36% of samples stated that they have not heard about HPV vaccination, while others had heard from health-care workers, family members, friends, or television, but their knowledge was inadequate. In all the three groups, there was significant improvement in level of knowledge, but there was no significant difference in attitude. The posttest knowledge scores of parents educated with short film were significantly more than the other two interventions. Conclusion: Online educational programs were found to be effective in improving the knowledge of parents on HPV vaccination and of the three methods; short film was more effective than the other two methods.

Human Papillomavirus Vaccinations During the COVID-19 Pandemic in Middle Schools in the Rio Grande Valley of Texas.

This quasi-experimental study (a community-based, physician-led human papillomavirus [HPV] education campaign and school-based vaccination program) followed 6481 students at eight Pharr-San Juan-Alamo Independent School District (Rio Grande Valley, Texas) middle schools between August 2016 and March 2021. We describe the successes and challenges experienced during the COVID-19 pandemic. HPV vaccine initiation and completion rates increased 1.29-fold and 1.47-fold, respectively, between June 2019 and March 2021. Between March 2020 and March 2021, 268 HPV vaccine doses were provided through 24 school-based interventions. Our program continued successes seen in increasing HPV vaccination rates and reducing possible HPV-associated cancers. (Am J Public Health. 2022;112(9):1269-1272. https://doi.org/10.2105/AJPH.2022.306970).

Population-Based Incidence of Guillain-Barré Syndrome During Mass Immunization With Viral Vaccines: A Pooled Analysis.

Misunderstanding temporal coincidence of adverse events during mass vaccination and invalid assessment of possible safety concerns have negative effects on immunization programs, leading to low immunization coverage. We conducted this systematic review and meta-analysis to identify the incidence rates of GBS that are temporally associated with viral vaccine administration but might not be attributable to the vaccines. By literature search in Embase and PubMed, we included 48 publications and 2,110,441,600 participants. The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination, equally 2.47 per 100,000 person-year (95%CI: 2.14 to 2.81). Subgroup analyses illustrated that the pooled rates were 2.77 per million persons (95%CI: 2.47 to 3.07) for individuals who received the influenza vaccine and 2.44 per million persons (95%CI: 0.97 to 3.91) for human papillomavirus (HPV) vaccines, respectively. Our findings evidence the GBS-associated safety of virus vaccines. We present a reference for the evaluation of post-vaccination GBS rates in mass immunization campaigns, including the SARS-CoV-2 vaccine.

Adolescent girls' recommendations for the design of a human papillomavirus vaccination program in Sindh, Pakistan: a qualitative study.

PURPOSE: Vaccination of adolescent girls against human papillomavirus (HPV) significantly reduces the incidence of cervical cancer. HPV vaccines are available in Pakistan but plans to develop HPV vaccination program are at a nascent stage. We conducted a formative study to explore adolescent girls' knowledge and perspectives on HPV and cervical cancer and collect their recommendations for implementing an HPV vaccination program in their community. METHODS: Using qualitative exploratory study design, we conducted four focus group discussions (FGDs) with 12 adolescent girls per group in District West, Karachi. We recruited unmarried girls aged 16-19 years from schools and community settings between May-December 2020. Data analysis was done using NVivo. RESULTS: Overall, participants displayed a positive attitude toward HPV vaccine. However, they were unfamiliar with basic concepts related to female reproductive health. Female relatives were indicated as girls' preferred point of contact for discussions on HPV and cervical cancer, but fathers were portrayed as decision-making authority on vaccination. Participants indicated vaccine hesitancy among parents may affect HPV vaccination uptake. Girls suggested individual household visits and community-based camps as strategies for successful implementation of HPV vaccination program. A solid foundation of trust between girls' families, program managers, and other stakeholders emerged as a key asset for the program's success. CONCLUSION: Adolescent girls' suggestions of informing key decision-makers in the family (particularly fathers) of the benefits of HPV vaccination, establishing trust with vaccine providers, and increasing accessibility of vaccinations should be explored for successful implementation of an HPV vaccination program in Pakistan.

Human Papillomavirus vaccination clinical decision support for young adults in an upper midwestern healthcare system: a clinic cluster-randomized control trial.

INTRODUCTION: Human papillomavirus (HPV) vaccination rates are low in young adults. Clinical decision support (CDS) in primary care may increase HPV vaccination. We tested the treatment effect of algorithm-driven, web-based, and electronic health record-linked CDS with or without shared decision-making tools (SDMT) on HPV vaccination rates compared to usual care (UC). METHODS: In a clinic cluster-randomized control trial conducted in a healthcare system serving a largely rural population, we randomized 34 primary care clinic clusters (with three clinics sharing clinicians randomized together) to: CDS; CDS+SDMT; UC. The sample included young adults aged 18-26 due for HPV vaccination with a study index visit from 08/01/2018-03/15/2019 in a study clinic. Generalized linear mixed models tested differences in HPV vaccination status 12 months after index visits by study arm. RESULTS: Among 10,253 patients, 6,876 (65.2%) were due for HPV vaccination, and 5,054 met study eligibility criteria. In adjusted analyses, the HPV vaccination series was completed by 12 months in 2.3% (95% CI: 1.6%-3.2%) of CDS, 1.6% (95% CI: 1.1%-2.3%) of CDS+SDMT, and 2.2% (95% CI: 1.6%-3.0%) of UC patients, and at least one HPV vaccine was received by 12 months in 13.1% (95% CI: 10.6%-16.1%) of CDS, 9.2% (95% CI: 7.3%-11.6%) of CDS+SDMT, and 11.2% (95% CI: 9.1%-13.7%) of UC patients. Differences were not significant between arms. Females, those with prior HPV vaccinations, and those seen at urban clinics had significantly higher odds of HPV vaccination in adjusted models. DISCUSSION: CDS may require optimization for young adults to significantly impact HPV vaccination. TRIAL REGISTRATION: clinicaltrials.gov NCT02986230, 12/6/2016.

Disparities in human papillomavirus vaccination coverage in the United States, National Health and Nutrition Examination Survey, January 2017-March 2020.

BACKGROUND: We assessed disparities in HPV vaccination coverage by sociodemographic characteristics in the United States. METHODS: Using 2017-March 2020 National Health and Nutrition Examination Survey data, we estimated vaccination coverage of ≥ 1 dose of HPV vaccine by race/ethnicity and poverty, insurance, and nativity status for females and males aged 9-14, 15-19, and 20-29 years. RESULTS: Among those aged 9-14 years, coverage among non-Hispanic Black (NHB), Hispanic, and non-Hispanic Asian (NHA) females (40.0%, 33.6%, 34.0%) and males (27.1%, 35.3%, 30.9%) was higher than non-Hispanic White (NHW) females (26.5%) and males (25.2%). Among those aged 15-19 and 20-29 years, coverage varied among NHB, Hispanic, and NHA compared to NHW females and was lower among NHB, Hispanic, and NHA than NHW males. Coverage was lower among uninsured than insured in most comparisons. CONCLUSIONS: HPV vaccination coverage varied by race/ethnicity and other characteristics. Efforts are needed to increase HPV vaccination coverage in all populations.

Impact of the COVID-19 Pandemic on Human Papillomavirus Vaccination in Brazil.

Objective: To analyze the number of applied HPV vaccine doses before (from April 2019 to March 2020) and after (from April 2020 to September 2020) social distancing measures in response to the COVID-19 pandemic in states and regions of Brazil. Methods: Ecological time-series study, using data from the Brazilian National Immunization Program (PNI). Using the Mann-Whitney test, we evaluated the difference between the median number of applied doses during the periods April 2019 to March 2020 and from April 2020 to September 2020. Spatial analysis identified clusters with a high or low percentage reduction in the median applied doses. Prais-Winsten regression models identified temporal trends in the applieddoses from both periods. Results: There was a significant reduction in the median HPV vaccine doses applied, formation of spatial clusters and, after a sharp drop in the number of applieddoses during the months following social distancing. There was a tendency to increase the applied vaccines doses. Conclusion: The COVID-19 pandemic resulted in reduction of the number of HPV vaccine doses applied as a possible effect of restrictive measures caused by the pandemic.

Adaptation of patients diagnosed with human papillomavirus: a grounded theory study.

BACKGROUND: Human papillomavirus is the most common cause of sexually transmitted diseases. Various studies report that positive human papillomavirus diagnosis results in psychosexual issues for the infected and reduces their quality of life. However, the adaptation of the infected has not been addressed yet. The present study aims to identify the process by which individuals infected with human papillomavirus adapt to their disease. METHOD: This is a qualitative work of research with a grounded theory design. The setting of the study was the skin clinic of Shahid Faghihi Hospital in Shiraz. The participants consisted of 27 individuals: 18 patients, 3 doctors, 2 counselors, and 4 spouses of patients. The subjects were selected via purposeful and theoretical sampling method until data saturation was reached. Data were collected through face-to-face, in-depth, semi-structured interviews from April 2019 to December 2020. The collected data were analyzed using Corbin and Strauss's method (2015) and MAXQDA 2018. RESULTS: The theory which emerged from the data was "trying to maintain resilience in the absence of psychological security." Analysis of data showed the main concern of participants in adapting to their diagnosis with human papillomavirus was "life stress". "Stigma and ignorance" was found to be a contextual condition and "paradox in support" was an intervening condition in the patients' adaptation. The patients' action/interaction responses to their main concern in the context in question were "emotional confrontation" and "maintaining resilience." The outcome was "oscillation between tension and tranquility." CONCLUSION: The present study explains the process by which patients with human papillomavirus adapt to their condition. Identification of the concerns of patients with human papillomavirus and the factors which affect their adaptation can help healthcare policy-makers and providers develop effective support plans in order to increase patients' quality of life. Early interventions, e.g. counseling care providers to modify their behaviors toward alleviating the psychosexual tension of the infected, can facilitate the adaptation of the infected and decrease the consequences of the infection for them.

Human papillomavirus (HPV) is the most common cause of sexually transmitted diseases. Almost all men and women get the infection at least once throughout their lives. The high-risk types of HPV account for about 5% of cancer cases globally. HPV can cause anogenital cancers and warts in both genders. In this grounded theory study, we conducted 27 in-depth interviews with Iranian patients, their spouses, and health care providers from April 2019 to December 2020. The collected data were analyzed using Corbin and Strauss's method (2015) and MAXQDA 2018. The participants were concerned about tension in family relationships, being stigmatized, getting cancer, recurrence of warts, transferring their disease to others, and changes in the appearance of their genitalia. They stated that HPV is regarded as a shameful disease in society. Most of the participants said they had never heard anything about HPV. The patients' action/interaction responses to their concerns were "emotional confrontation" and "maintaining resilience." These strategies helped the patients recover some of their tranquility. However, some of patients' concerns were persistent and kept them oscillating between tension and tranquility. An understanding of the patients' perception of their disease is essential to development of effective educational interventions to change patients' perspective on their situation and improve their recovery. Furthermore, because of the low level of public awareness about HPV and sexual health and the flow of misinformation to the infected, it is recommended that educational interventions focus on the patients' concerns.

Acceptance and Willingness to Pay for Vaccine Against Human Papilloma Virus (HPV) Among Parents of Boys in Central Vietnam.

Human papilloma virus (HPV) vaccine for adolescents was recommended as an effective prevention strategy of HPV-related cancers. In Vietnam, HPV vaccination has not been introduced to male adolescent. This study was conducted to examine the acceptance of having boys vaccinated against HPV and its underlying reasoning, and to identify their parent's willingness to pay (WTP) for HPV vaccination in central Vietnam. 785 parents of boys were directly interviewed based on a structured questionnaire. Parent's acceptability of HPV vaccine for their sons was identified by one question with response on 3-point scale (agree, don't know, and disagree). Multivariate logistic regression model was used to determine contributing factors to participant's acceptance. Bidding game method was applied to elicit WTP values for HPV vaccination with initial bid of 161.2 USD. The results showed that 49.2% of parents agreed to have their sons vaccinated against HPV. Factors that influenced parent's acceptance including son's age older than 12 years (OR = 1.5; 95% CI: 1.08-1.98); being eldest son (OR = 1.6; 95% CI: 1.13-2.19), being mother (OR = 1.4; 95% CI: 1.01-1.91), parents with high educational level (OR = 1.7; 95% CI: 1.11-2.47) and their knowledge of HPV and HPV vaccine (OR = 1.8; 95% CI: 1.23-2.65). Average WTP value for full doses of HPV vaccine was 137.5 USD, ranging between 9 USD and 188.3 USD. Parents' knowledge of HPV and HPV vaccine was the only factor affecting WTP value (Rho: 0.11; p-value: 0.030). The findings suggest a strategy be introduced for HPV vaccination to male adolescents in Vietnam.

Disentangling the Role of Religiosity in Human Papillomavirus Vaccination Amidst COVID-19 Pandemic.

Religion is a complex and sociocultural driver of human papillomavirus (HPV) vaccination decisions, but its exact role has been mixed/unclear. We used a cross-sectional study of 342 Christian parents to examine the associations between the three domains of religiosity (organizational, non-organizational, and intrinsic) and the intention to (i) seek HPV information and (ii) receive the HPV vaccine. Organizational religiosity was the only domain that was positively associated with information-seeking intention regardless of the type of covariates included. Mixed findings in the association between religiosity and HPV vaccination decisions may depend on the religiosity domain being assessed.