Prevalence and Genotype Distribution of Potential High-Risk and High-Risk Human Papillomavirus among Women attending Selected Reproductive Health Clinics in Lake Victoria Basin-Kenya: A Cross-sectional Study (preprint)

Background Persistent human papillomavirus (HPV) infection is considered the primary etiological factor for invasive cervical cancer. Understanding the epidemiology of circulating potential high-risk (HR) and HR HPV strains is essential in updating epidemiological knowledge and recommendations on genotype-specific vaccination development. In Lake Victoria Basin-LVB (Kisumu and Siaya Counties, Kenya), both the HIV burden, the post-COVID-19 pandemic environment and the population growth point to the need to study the current circulating strains. This study determined the prevalence and factors associated with Potential HR/HR HPV among women attending selected reproductive health clinics in LVB. The prevalence of Potential HR/HR HPV, genotype-specific distributions, and implications to the current HPV vaccination ongoing within Kenya are discussed. Methods A cross-sectional facility-based survey made up of 434 women aged 16-68 years was carried out in two selected facilities in the Urban-Kisumu County (Jaramogi Oginga Odinga Teaching and Referral Hospital-[JOOTRH] and rural-Siaya County (Gobei Health Center). Structured questionnaires were conducted to collect participant clinical and social characteristics. Cervical specimens were collected by registered reproductive health nurses and HPV genotyping was carried out using RIATOL HPV genotyping qPCR assay. Descriptive statistics followed by logistic binary regression was done using R version 4.3.2 Results The overall prevalence of potential HR/HR HPV among women attending the selected reproductive health clinics was reported at 36.5% (158/434). Specifically, in the rural setting, Gobei Health Center, the prevalence was 41.4% (41/99) while in the urban setting-JOOTRH, it was 34.6% (117/335). The most prevalent potential HR/HR HPV are 52, 67, 16, 31, 39, 45, and 31 for both HIV-positive and negative women and either in rural-Gobei Health Centre and Urban-JOOTRH. In this study, HIV status was not associated with potential HR/HR HPV among women attending. Age was the main factor associated with HPV infection among HIV-positive and negative women attending the selected reproductive health clinics in rural-urban Lake Victoria Basin, with women between the age of 30-39 having the highest risk (AOR=0.3, CI:0.2-0.7, p<0.001). Conclusion In both rural and urban regions, potential HR/HR HPV infection among individuals attending reproductive health clinics at the selected facilities remains common. The study identifies the need for effective implementation and clinical follow-up process of cervical cancer control program in the Lake Victoria Basin.

Significant specificity of TruScreen in cervical cytology of ASC and LSIL women with incomplete cervical transformation zone type during COVID-19 post-pandemic in China: a prospective study (preprint)

Objective: To evaluate the efficacy of TruScreen (TS) detecting cervical intraepithelial neoplasia (CIN) in cytology of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL) women during COVID-19 post-pandemic. Design: Prospective, single-center study. Setting: Changsha, China. Population: ASC and LSIL women from December 2020 to May 2021. Methods: Participants underwent TS, colposcopy examination and biopsy in turn. Diagnostic value of TS, high-risk human papillomavirus (hrHPV) and TS combined with hrHPV were compared. Differences of TS regarding cervical transformation zone (TZ) type and menopause, correlations between TS and p16, Ki-67 were assessed. Main outcome measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under curve (AUC) for diagnostic value. Spearman coefficient for correlation. Results: A total of 483 patients were enrolled. Specificity of TS detecting CIN1+, CIN2+, CIN3+ were 77.1% (95% CI, 70.4%-82.7%), 66.7% (95% CI, 61.5%-71.5%), 62.7% (95% CI, 57.8%-67.4%) and all were significantly higher than hrHPV test (P<0.001). TS had a high sensitivity (68.0% vs 52.0%, P>0.05) and significantly higher specificity (70.0% vs 48.5%, P<0.05) and NPV (89.6% vs 73.3%, P<0.05) in women with incomplete cervical TZ type (II and III) than TZ type I in detection of CIN2+. Conclusion: TS is an effective triage screening method for cervical cytology of ASC and LSIL women during COVID-19 post-pandemic, especially for incomplete cervical TZ type women. Funding: Supported by National Natural Science Foundation Project of China (81771546) and Hunan Science and Technology Innovation Project (2020SK53404). Keywords: TruScreen; Cervical cancer screening; Cervical transformation zone; CIN; COVID-19.

Unleashing the Power of Artificial Intelligence: Unraveling the Intricate Dynamics between Viral and Bacterial Infections, Immune Factors, COVID-19, and Cancer in Women's Health (preprint)

The intricate interplay between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health has garnered significant attention in recent research. This comprehensive study aimed to unravel the complex dynamics between these factors and provide valuable insights into their implications for women's health. Through meticulous analysis of available data, this study elucidated the prevalence of viral and bacterial infections in women, encompassing influential pathogens such as influenza, human papillomavirus, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. Additionally, it explored the relationship between specific cytokine types, including Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-γ), and Interleukin-10 (IL-10), and viral infections. The prevalence of various cancer types, such as breast cancer, lung cancer, colorectal cancer, ovarian cancer, and cervical cancer, was also assessed. Furthermore, this study examined the correlations between immune factors and viral infections, uncovering significant associations that shed light on the intricate interplay between immune responses and viral infections. Immune markers such as IL-6, TNF-α, IFN-γ, Interleukin-1beta (IL-1β), and Interleukin-12 (IL-12) exhibited diverse levels of correlation with specific viral infections. These findings hold promise for disease prognosis and treatment optimization. Additionally, the association between bacterial infections and women's health conditions was explored, revealing the impact of pathogens like Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis on gynecological infections, reproductive disorders, and other relevant conditions. This highlights the need for effective strategies to prevent and manage bacterial infections, aiming to mitigate their adverse effects on women's health. In the context of COVID-19, this study investigated immune factors as predictors of disease outcomes in women. Various cytokines, including IL-6, TNF-α, IL-1β, IFN-γ, IL-10, IL-8, IL-4, IL-2, IL-12, and IL-17, demonstrated associations with disease severity, offering potential prognostic markers for identifying individuals at higher risk of severe illness. Furthermore, the relationship between viral and bacterial infections and cancer incidence in women was explored. Viral infections, such as human papillomavirus and influenza, showed associations with specific cancer types, including breast cancer, cervical cancer, lung cancer, skin cancer, and stomach cancer. Bacterial infections, such as Staphylococcus aureus and Escherichia coli, were linked to ovarian cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, and esophageal cancer. These findings provide valuable insights into the potential role of infectious etiologies in cancer development among women. In conclusion, this comprehensive study unveils the intricate dynamics between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health. The findings emphasize the importance of considering the interconnectedness of these factors to enhance disease prevention, diagnosis, and treatment strategies in women. Further research is warranted to unravel the underlying mechanisms and translate these findings into clinical applications.

Genome-wide Association Study of Long COVID (preprint)

Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction(3-5). The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative(6,7) to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity(6), lung function(8), and cancers(9), suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.

No woman left behind: achieving cervical cancer elimination among women living with HIV.

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy.

Perceived barriers to cervical cancer screening and motivators for at-home human papillomavirus self-sampling during the COVID-19 pandemic: Results from a telephone survey.

Background: Home-based self-sampling for human papillomavirus (HPV) testing may be an alternative for women not attending clinic-based cervical cancer screening. Methods: We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women aged 30-65 and under-screened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups, and determined statistical significance at p<0.05. Results: Over half of 233 survey participants reported that clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The last two factors were significantly more prevalent among Spanish vs English speakers (66.4% vs 30% (p=0.000) and 69.9 vs 52.2% (p=0.006), respectively). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%), and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish vs English speakers (79.6% vs 53.38%, p=0.001) and among patients with elementary education or below. Conclusions: The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments, and ease of using kits. HPV self-sampling kits may reduce barriers among under-screened women in a safety-net system. Funding: This study is supported by a grant from the National Institute for Minority Health and Health Disparitie s (NIMHD, R01MD013715, PI: JR Montealegre). Clinical trial number: NCT03898167.

HPV prevalence and genotype distribution among women in eastern China during the Covid-19 pandemic.

Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26-35, 36-45, 46-55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.

Barriers and facilitators of HPV vaccination in sub-saharan Africa: a systematic review.

BACKGROUND: Human Papilloma Virus (HPV) is the most common sexually transmitted infection worldwide. Globally, both men and women have a 50% risk of being infected at least once in their life. HPV prevalence is among the highest in sub-Saharan Africa (SSA), at an average of 24%. HPV causes different types of cancers, including cervical cancer (CC), which is the leading cause of cancer deaths among women in SSA. HPV-vaccination has been proven to be effective in reducing HPV induced cancers. SSA countries are delayed in reaching the WHO's target of fully vaccinating 90% of girls within the age of 15 by 2030. Our systematic review aims to identify barriers and facilitators of HPV-vaccination in SSA to inform national implementation strategies in the region. METHODS: This is a mixed method systematic review based on the PRISMA statement and The Joanna Briggs Institute Reviewers' Manual. Search strategies were adapted to each selected database: PubMed/MEDLINE, Livivo, Google Scholar, Science Direct, and African Journals Online for papers published in English, Italian, German, French and Spanish between 1 December 2011 and 31 December 2021. Zotero and Rayyan were the software used for data management. The appraisal was conducted by three independent reviewers. RESULTS: A total of 20 articles were selected for appraisal from an initial 536 articles. Barriers included: limited health system capacities, socio-economic status, stigma, fear and costs of vaccines, negative experience with vaccinations, COVID-19 pandemic, lack of correct information, health education (HE) and consent. Additionally, we found that boys are scarcely considered for HPV-vaccination by parents and stakeholders. Facilitators included: information and knowledge, policy implementation, positive experience with vaccinations, HE, stakeholders' engagement, women's empowerment, community engagement, seasonality, and target-oriented vaccination campaigns. CONCLUSIONS: This review synthesizes barriers and facilitators of HPV-vaccinations in SSA. Addressing these can contribute to the implementation of more effective HPV immunization programs targeted at eliminating CC in line with the WHO 90/70/90 strategy. REGISTRATION AND FUNDING: Protocol ID: CRD42022338609 registered in the International Prospective Register of Systematic Reviews (PROSPERO). Partial funds: German Centre for Infection research (DZIF) project NAMASTE: 8,008,803,819.

Factors associated with HPV vaccine acceptability and hesitancy among Black mothers with young daughters in the United States.

Introduction: Compared to other-race peers, Black women are disproportionately impacted by human papillomavirus [HPV] infection, related health outcomes, and cervical cancer mortality as a result of suboptimal HPV vaccine uptake during adolescence. Few studies in the United States have examined psychosocial determinants of HPV vaccine acceptability and hesitancy among Black parents. The current study integrated the health belief model and the theory of planned behavior to evaluate the extent to which psychosocial factors are associated with pediatric HPV vaccination intentions among this population. Methods: Black mothers (N = 402; age range = 25 to 69 years, M = 37.45, SD = 7.88) of daughters ages 9 to 15 years completed an online survey assessing HPV infection and vaccine beliefs and attitudes across four domains: Mother's HPV Perceptions, Mother's Vaccine Attitudes, Cues to Action, and Perceived Barriers to HPV Vaccination. Participants indicated their willingness to vaccinate their daughter on a 5-level ordinal scale ("I will definitely not have my daughter get the vaccine" to "I will definitely have my daughter get the vaccine") which was dichotomously recoded for binomial logistic regressions. Results: Half of the sample (48%) intended to vaccinate their daughter. Number of daughters, mother's HPV vaccine status, perceived HPV vaccine benefits, HPV vaccine safety concerns, pediatric HPV vaccine peer norms, and doctor recommendations emerged as independent factors of Black mothers' intentions to vaccinate their daughters against HPV when controlling for all other factors. Discussion: In addition to medical training to increase doctor recommendation of the HPV vaccine for Black girls, population-tailored public health messaging aimed at promoting HPV vaccine acceptance among Black mothers is urgently needed. This messaging should engage community support and emphasize the benefits of vaccination for adolescent Black girls while also addressing parental concerns regarding the safety of pediatric HPV vaccination.

Imprecision in adverse event reports following immunization against HPV in Japan and COVID-19 in the USA, UK, and Japan-and the effects of vaccine hesitancy and government policy.

INTRODUCTION: Erroneous reports of adverse events following immunization (AEFIs) likely exacerbated the 2013 collapse of Japan's HPV immunization program. A similar phenomenon characterized the first months of COVID-19 immunization programs in the USA, UK, and Japan with high rates of reported anaphylaxis. These reports illustrate the susceptibility of supposedly objective medical judgments to public anxiety. PURPOSE AND METHODS: This study documents inaccuracies in reported AEFIs using three quantitative methods. RESULTS: One of these quantitative methods revealed that false-positive rates for anaphylaxis reports following HPV and later COVID-19 vaccination ranged from 74 to 91 percent. However, unlike HPV vaccinations in Japan, anaphylaxis reports following COVID-19 vaccines fell in Japan, the USA and the UK in the latter months of 2021. Nevertheless, false-positive rates for anaphylaxis reports remained high, suggesting a high degree of imprecision in serious AEFI reports from many countries for many vaccines. Japan's HPV immunization program indicates that media reports, patient hesitancy, healthcare providers' perspectives on vaccine safety, and consistency of government messaging, all influence report number and accuracy. A parallel publication analyzes in depth how such factors affect AEFI reports. CONCLUSION: Confidence in the safety of the COVID-19 vaccines may have been bolstered trough rapid monitoring of AEFI reports and communication of these findings. This may partly explain the different trajectories of serious AEFI following HPV immunizations in Japan and COVID-19 immunizations in the USA, UK, and Japan.

Exploring the factors contributing to low vaccination uptake for nationally recommended routine childhood and adolescent vaccines in Kenya.

BACKGROUND: Vaccination remains the most effective means of reducing the burden of infectious disease among children. It is estimated to prevent between two to three million child deaths annually. However, despite being a successful intervention, basic vaccination coverage remains below the target. About 20 million infants are either under or not fully vaccinated, most of whom are in Sub-Saharan Africa region. In Kenya, the coverage is even lower at 83% than the global average of 86%. The objective of this study is to explore the factors that contribute to low demand or vaccine hesitancy for childhood and adolescent vaccines in Kenya. METHODS: The study used qualitative research design. Key Informant Interviews (KII) was used to obtain information from national and county-level key stakeholders. In-depth Interviews (IDI) was done to collect opinions of caregivers of children 0-23 months and adolescent girls eligible for immunization, and Human papillomavirus (HPV) vaccine respectively. The data was collected at the national level and counties such as Kilifi, Turkana, Nairobi and Kitui. The data was analyzed using thematic content approach. A total of 41 national and county-level immunization officials and caregivers formed the sample. RESULTS: Insufficient knowledge about vaccines, vaccine supply issues, frequent healthcare worker's industrial action, poverty, religious beliefs, inadequate vaccination campaigns, distance to vaccination centers, were identified as factors driving low demand or vaccine hesitancy against routine childhood immunization. While factors driving low uptake of the newly introduced HPV vaccine were reported to include misinformation about the vaccine, rumors that the vaccine is a form of female contraception, the suspicion that the vaccine is free and available only to girls, poor knowledge of cervical cancer and benefits of HPV vaccine. CONCLUSIONS: Rural community sensitization on both routine childhood immunization and HPV vaccine should be key activities post COVID-19 pandemic. Likewise, the use of mainstream and social media outreaches, and vaccine champions could help reduce vaccine hesitancy. The findings are invaluable for informing design of context-specific interventions by national and county-level immunization stakeholders. Further studies on the relationship between attitude towards new vaccines and connection to vaccine hesitancy is necessary.

Exploring HPV vaccination policy and payer strategies for opportunities to improve uptake in safety-net settings.

Introduction: We explored priorities and perspectives on health policy and payer strategies for improving HPV vaccination rates in safety-net settings in the United States. Methods: We conducted qualitative interviews with policy and payer representatives in the greater Los Angeles region and state of New Jersey between December 2020 and January 2022. Practice Change Model domains guided data collection, thematic analysis, and interpretation. Results: Five themes emerged from interviews with 11 policy and 8 payer participants, including: (1) payer representatives not prioritizing HPV vaccination specifically in incentive-driven clinic metrics; (2) policy representatives noting region-specific HPV vaccine policy options; (3) inconsistent motivation across policy/payer groups to improve HPV vaccination; (4) targeting of HPV vaccination in quality improvement initiatives suggested across policy/payer groups; and (5) COVID-19 pandemic viewed as both barrier and opportunity for HPV vaccination improvement across policy/payer groups. Discussion: Our findings indicate opportunities for incorporating policy and payer perspectives into HPV vaccine improvement processes. We identified a need to translate effective policy and payer strategies, such as pay-for-performance programs, to improve HPV vaccination within safety-net settings. COVID-19 vaccination strategies and community efforts create potential policy windows for expanding HPV vaccine awareness and access.

Deciphering the Relationship between SARS-CoV-2 and Cancer.

Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, ß-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.

Recent Human Papillomavirus Vaccination is Associated with a Lower Risk of COVID-19: A US Database Cohort Study.

OBJECTIVE: To explore the association between human papillomavirus (HPV) vaccination and risk of coronavirus disease 2019 (COVID-19). Specifically, our study aimed to test the hypothesis that HPV vaccination may also induce trained immunity, which would potentially reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and improve clinical outcomes. BACKGROUND: Several vaccines have been reported to trigger non-specific immune reactions that could offer protection from heterologous infections. A recent case report showed that verruca vulgaris regressed after COVID-19, suggesting a possible negative association between COVID-19 and HPV infection. METHODS: We enrolled 57,584 women with HPV vaccination and compared them with propensity score-matched controls who never received HPV vaccination in relation to the risk of COVID-19 incidence. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses stratified by age, race, comorbid asthma, and obesity were performed. RESULTS: The risk of COVID-19 incidence was significantly lower in those who had recently received the HPV vaccine (within 1 year after HPV vaccination, aHR: 0.818, 95% CI 0.764-0.876; within 1-2 years after HPV vaccination, aHR: 0.890, 95% CI 0.824-0.961). Several limitations were recognized in this study, including residual confounding, problems of misclassification due to the use of electronic health record data, and that we were unable to keep track of the patients' HPV infection status and the HPV antibody levels in those who had received the vaccine. CONCLUSIONS: Recent HPV vaccination was associated with a lower risk of incident COVID-19 and hospitalization. Based on the promising protective effect of HPV vaccine shown in this study, these findings should be replicated in an independent dataset. Further studies are needed to provide a better understanding of the underlying mechanisms and the differences in risks among 2-, 4-, or 9-valent HPV vaccine recipients.

Patterns of HPV vaccine hesitancy among catch-up generations in Japan: A descriptive study.

BACKGROUND: Cervical cancer is a preventable disease caused by human papillomavirus (HPV). The HPV vaccine uptake in Japan has been slow since the Ministry of Health, Labour and Welfare suspended the recommendation for proactive HPV vaccination in 2013. In April 2022, Japan initiated catch-up vaccinations for women who missed the opportunity to receive the HPV vaccine. However, as of September 2022, very few women had received catch-up vaccination, raising concerns about vaccine hesitancy in the target population. It is necessary to understand the thinking and motivation of the target population to develop effective strategies to improve vaccination rates. Therefore, using cluster analysis, this study aimed to clarify the pattern of HPV vaccine hesitancy among the catch-up generations in Japan. METHODS: This descriptive study was based on an Internet survey completed by 3,790 women in Japan aged over 18 years who were eligible for catch-up vaccination and had not yet received an HPV vaccine. Participants were asked about their intention and thinking about the HPV vaccine and descriptive norms on vaccination intention. Cluster analysis using k-means clustering was performed to clarify these patterns. RESULTS: Cluster analysis revealed three hesitancy patterns: acceptance, neutral and refusal. The acceptance group, with high intention, comprised 28.2% of the participants, and students and a high-income level mainly dominated this group. The refusal group, with negative thinking and low intention, accounted for 20.1% and was more prevalent among workers and the unemployed. The neutral group, with neutral thinking and intention, accounted for 51.6%. The perceived effect of descriptive norms on vaccination intention was large in the acceptance group but small in the refusal group. CONCLUSION: HPV vaccine awareness promotion strategies must be based on the characteristics of each group and the different distributions of sociodemographic factors.

COVID-19 as a catalyst for reimagining cervical cancer prevention.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

Updated Review of Major Cancer Risk Factors and Screening Test use in the United States, with a Focus on Changes During the COVID-19 Pandemic.

We present national and state representative prevalence estimates of modifiable cancer risk factors, preventive behaviors and services, and screening, with a focus on changes during the COVID-19 pandemic. Between 2019 and 2021, current smoking, physical inactivity, and heavy alcohol consumption declined, and human papillomavirus vaccination and stool testing for colorectal cancer screening uptake increased. In contrast, obesity prevalence increased, while fruit consumption and cervical cancer screening declined during the same timeframe. Favorable and unfavorable trends were evident during the second year of the COVID-19 pandemic that must be monitored as more years of consistent data are collected. Yet disparities by racial/ethnic and socioeconomic status persisted, highlighting the continued need for interventions to address suboptimal levels among these population subgroups.

A synthetic delivery vector for mucosal vaccination (preprint)

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.

Does HPV vaccination initiation at age 9, improve HPV initiation and vaccine series completion rates by age 13?

Vaccination for Human Papillomavirus (HPV) is important to reduce rates of cervical and oropharyngeal cancer. We aimed to evaluate if a program to initiate HPV vaccination at 9 years improved initiation and completion rates by 13 years of age. Data on empaneled patients aged 9-13 years from January 1, 2021 to August 30, 2022 were abstracted from the electronic health record. Primary outcome measures included HPV vaccination initiation and series completion by 13 years of age. The secondary outcome measure was missed opportunities for HPV vaccination. In total, 25,888 patients were included (12,433 pre-intervention, and 13,455 post-intervention). The percentage of patients aged 9-13 with an in-person visit who received at least 1 dose of HPV vaccine increased from 30% pre-intervention to 43% post-intervention. The percentage of patients who received 2 doses of vaccine increased from 19.3% pre-intervention to 42.7% post-intervention. For the overall population seen in-person, initiation of HPV vaccination by age 13 years increased from 42% to 54%. HPV completion increased as well (13% to 18%). HPV vaccination initiation at 9 years of age may be an acceptable and effective approach to improving vaccination rates.

HPV vaccine recommendations by age: A survey of providers in federally qualified health centers.

Clinician recommendation remains a critical factor in improving HPV vaccine uptake. Clinicians practicing in federally qualified health centers were surveyed between October 2021 and July 2022. Clinicians were asked how they recommended HPV vaccination for patients aged 9-10, 11-12, 13-18, 19-26, and 27-45 y (strongly recommend, offer but do not recommend strongly, discuss only if the patient initiates the conversation, or recommend against). Descriptive statistics were assessed, and exact binomial logistic regression analyses were utilized to examine factors associated with HPV vaccination recommendation in 9-10-y-old patients. Respondents (n = 148) were primarily female (85%), between the ages of 30-39 (38%), white, non-Hispanic (62%), advanced practice providers (55%), family medicine specialty (70%), and practicing in the Northeast (63%). Strong recommendations for HPV vaccination varied by age: 65% strongly recommended for ages 9-10, 94% for ages 11-12, 96% for ages 13-18, 82% for age 19-26, and 26% for ages 27-45 y. Compared to Women's Health/OBGYN specialty, family medicine clinicians were less likely to recommend HPV vaccination at ages 9-10 (p = .03). Approximately two-thirds of clinicians practicing in federally qualified health centers or safety net settings strongly recommend HPV vaccine series initiation at ages 9-10. Additional research is needed to improve recommendations in younger age groups.