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.

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).

COVID-19 and human papillomavirus: Paradoxical immunity.

Coronavirus disease 2019 (COVID-19) is a multisystemic disease that can cause progressive lung failure, organ dysfunction, and coagulation disorder associated with high mortality and morbidity. COVID-19 is known to either primarily cause skin symptoms or increase existing skin diseases. Human papillomavirus (HPV) is a DNA virus that can cause benign and malignant neoplasms. Mucocutaneous verruca vulgaris are common benign lesions of HPV. Here, we report a case of verruca vulgaris regressed after COVID-19.

Contemplating HPV vaccination in Japan during the time of COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic has been growing, including in Japan where it has been estimated that as many as 3.1% of patients positive for new CoV strain SARS-CoV-2 might die of COVID-19-related respiratory failure. Meanwhile, human papillomavirus (HPV) is spreading in Japan. The fatality rate for HPV-associated cancers after infection with HPV is as much as that for COVID-19 in Japan, although the time to disease is much longer for HPV. Among advanced countries, the cervical cancer screening rate in Japanese females is very low. The Japanese Ministry of Health, Labor and Welfare (MHLW) suspended its official recommendation for HPV vaccination in June 2013 due to alleged adverse post-vaccination events in several young girls, such as chronic pain and motor impairment, which were repeatedly reported in the media. Subsequently, the rate for vaccinating girls plummeted from approximately 70% to the current rate of 1% or less. Women should accept HPV vaccination for the eventual prevention of cervical cancer with the same passion they are for COVID-19 testing.

The European response to the WHO call to eliminate cervical cancer as a public health problem.

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.