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Preventive Medicine Jul 2023Using a cluster-randomized trial design, we aimed to evaluate a complex intervention to increase uptake of human papillomavirus (HPV) vaccination in schools. The study... (Randomized Controlled Trial)
Randomized Controlled Trial
Using a cluster-randomized trial design, we aimed to evaluate a complex intervention to increase uptake of human papillomavirus (HPV) vaccination in schools. The study was undertaken in high schools in Western Australia and South Australia between 2013 and 2015 with adolescents aged 12-13 years. Interventions included education, shared decision-making, and logistical strategies. The main outcome was school vaccine uptake. Secondary outcomes included consent forms returned and mean time to vaccinate 50 students. We hypothesised that a complex intervention would increase 3-dose HPV vaccine uptake. We recruited 40 schools (21 intervention, 19 control) with 6, 967 adolescents. There was no difference between intervention and control (3-dose mean 75.7% and 78.9%, respectively). Following adjustment for baseline covariates, absolute differences in coverage in favour of the intervention group were: dose 1, 0.8% (95% CI, -1.4,3.0); dose 2, 0.2% (95% CI, -2.7, 3.1); dose 3, 0.5% (95% CI, -2.6, 3.7). The percentage of returned consent forms in intervention schools (91.4%) was higher than in control schools (difference: 6%, 95% CI, 1.4, 10.7). There was a shorter mean time to vaccinate 50 students at dose 3. The difference for dose 3 was 110 min (95% CI, 42, 177); for dose 2, 90 min (95% CI, -15, 196); and dose 1, 28 min (95% CI, -71, 127). Logs revealed the inconsistent implementation of logistical strategies. The intervention had no impact on uptake. Inadequate resourcing for logistical strategies and advisory board reluctance toward strategies with potential financial implications impacted the implementation of logistical components. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000404628, 14.04.2014. The study protocol was published in 2015 before data collection was finalised (Skinner et al., 2015). THE HPV.EDU STUDY GROUP: We would like to acknowledge the contributions to this study by members of the HPV.edu Study Group, including: Professor Annette Braunack-Mayer: Australian Centre for Health Engagement, Evidence and Values, School of Health and Society, Faculty of Arts, Social Sciences and Humanities, University of Wollongong, NSW, Australia; Dr. Joanne Collins: Women's and Children's Health Network and School of Medicine and Robinson Research Institute, University of Adelaide, SA, Australia; Associate Professor Spring Cooper: School of Public Health, City University of New York (CUNY), New York, NY, USA; Heidi Hutton: Telethon Kids Institute, University of Western Australia, WA, Australia; Jane Jones: Telethon Kids Institute, University of Western Australia, WA, Australia; Dr. Adriana Parrella: Women's and Children's Health Network and School of Medicine and Robinson Research Institute, University of Adelaide, SA, Australia; and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; Associate Professor David G. Regan: The Kirby Institute for Infection and Immunity in Society, Faculty of Medicine, UNSW Sydney, NSW, Australia; Professor Peter Richmond: Perth Children's Hospital, Child and Adolescent Health Service, Western Australia, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, WA, Australia, and School of Medicine, University of Western Australia, Perth, WA, Australia; Dr. Tanya Stoney: Telethon Kids Institute, University of Western Australia, WA, Australia. Contact for the HPV.edu study group: [email protected] or [email protected].
Topics: Child; Adolescent; Female; Humans; Human Papillomavirus Viruses; Australia; Papillomavirus Infections; Papillomavirus Vaccines; Child Health; Women's Health; Vaccination
PubMed: 37172767
DOI: 10.1016/j.ypmed.2023.107542 -
Cancer Epidemiology, Biomarkers &... Sep 2023Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We...
BACKGROUND
Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer.
METHODS
African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry.
RESULTS
Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes.
CONCLUSIONS
Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression.
IMPACT
Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.
Topics: Female; Humans; Human Papillomavirus Viruses; Cohort Studies; Papillomavirus Infections; Case-Control Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Papillomaviridae; Polymorphism, Single Nucleotide; Glypicans
PubMed: 37410084
DOI: 10.1158/1055-9965.EPI-23-0300 -
Viruses May 2024Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing... (Review)
Review
Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing to produce the full suite of viral mRNAs. These processes are controlled by a wide range of cellular RNA binding proteins (RPBs), including constitutive splicing factors and cleavage and polyadenylation machinery, but also factors that regulate these processes, for example, SR and hnRNP proteins. Like cellular RNAs, papillomavirus RNAs have been shown to bind many such proteins. The life cycle of papillomaviruses is intimately linked to differentiation of the epithelial tissues the virus infects. For example, viral late mRNAs and proteins are expressed only in the most differentiated epithelial layers to avoid recognition by the host immune response. Papillomavirus genome replication is linked to the DNA damage response and viral chromatin conformation, processes which also link to RNA processing. Challenges with respect to elucidating how RBPs regulate the viral life cycle include consideration of the orchestrated spatial aspect of viral gene expression in an infected epithelium and the epigenetic nature of the viral episomal genome. This review discusses RBPs that control viral gene expression, and how the connectivity of various nuclear processes might contribute to viral mRNA production.
Topics: RNA-Binding Proteins; Humans; Gene Expression Regulation, Viral; RNA, Viral; Papillomaviridae; Virus Replication; Viral Proteins; Papillomavirus Infections; Genome, Viral; Host-Pathogen Interactions; RNA, Messenger
PubMed: 38793664
DOI: 10.3390/v16050783 -
Human Vaccines & Immunotherapeutics Dec 2024Despite the ongoing global vaccination campaign aimed at preventing human papillomavirus (HPV) related health issues, the uptake of the HPV vaccine remains unacceptably... (Meta-Analysis)
Meta-Analysis Review
Despite the ongoing global vaccination campaign aimed at preventing human papillomavirus (HPV) related health issues, the uptake of the HPV vaccine remains unacceptably low in developing regions, particularly in sub-Saharan Africa (SSA). Therefore, this systematic review and meta-analysis aimed at determining the pooled prevalence and associated factors of HPV vaccine uptake among adolescent school girls in SSA. Electronic bio-medical databases were explored. Pooled prevalence, publication bias, meta-regression, sub-group, and sensitivity analysis were performed. The estimated pooled prevalence of HPV vaccine uptake was 28.53% [95% CI: (5.25, 51.81)]. Having good knowledge and a positive attitude was significantly associated with HPV vaccine uptake in SSA. Subgroup analysis revealed the highest uptake was 62.52% from Kenya and the lowest was 3.77% in Nigeria. The HPV vaccine uptake is low. It underscores the need for community education, school-based immunization, and education programs that promote the uptake of the vaccine to increase coverage.
Topics: Female; Humans; Adolescent; Papillomavirus Infections; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Vaccination; Human Papillomavirus Viruses; Africa South of the Sahara
PubMed: 38505959
DOI: 10.1080/21645515.2024.2326295 -
Microbiology Spectrum Aug 2023Infection with high-risk human papillomavirus (hrHPV) is well recognized as the main cause of cervical cancer. The recently developed Seegene Allplex HPV28 assay is a...
Comparison between the Roche Cobas 4800 Human Papillomavirus (HPV), Abbott RealTime High-Risk HPV, Seegene Anyplex II HPV28, and Novel Seegene Allplex HPV28 Assays for High-Risk HPV Detection and Genotyping in Mocked Self-Samples.
Infection with high-risk human papillomavirus (hrHPV) is well recognized as the main cause of cervical cancer. The recently developed Seegene Allplex HPV28 assay is a novel quantitative PCR (qPCR) assay designed to separately detect and quantify 28 distinct HPV genotypes in a fully automated and user-friendly manner. This study evaluated and compared the performance of this new assay with the performance of the Roche Cobas 4800, the Abbott RealTime high-risk HPV, and the Seegene Anyplex II HPV28 assays. A total of 114 mocked self-samples, i.e., semicervical samples collected by gynecologists using the Viba-Brush, were analyzed with all four HPV assays. Agreement in terms of detecting and genotyping HPV was assessed by the mean of the Cohen's kappa (κ) coefficient. Results of all four HPV assays agreed in 85.9% of the cases when using the Abbott RealTime manufacturer's recommended quantification cycle () cutoff for positivity (<32.00) and 91.2% when using an adapted range (32.00 to 36.00). An intercomparison of the included assays demonstrated an overall agreement ranging from 85.9 to 100.0% (κ = 0.42 to 1.00) when using the manufacturer's guidelines and 92.9 to 100.0% (κ = 0.60 to 1.00) with the adapted range. For all assays, highly significant, strongly positive Pearson correlations were shown between the values of positive test results. This study thereby shows high concordance between results of the included HPV assays on mocked self-samples. Based on these findings, we imply that the novel Allplex HPV28 assay demonstrates a comparable performance to those of available qPCR HPV assays, potentially providing opportunities for the simplification and standardization of future large-scale testing. This study proves that the novel Allplex HPV28 assay has a good diagnostic performance in comparison with the well-known, validated, and frequently used Roche Cobas 4800, Abbott RealTime, and Anyplex II HPV28 assays. According to our experience, the novel Allplex HPV28 assay had a user-friendly and automated workflow with short hands-on time, had an open platform which facilitates the use of add-on assays, and provided quick and easy-to-interpret results. Together with its ability to detect and quantify 28 HPV genotypes, the Allplex HPV28 assay could therefore potentially provide opportunities for the simplification and standardization of future diagnostic testing programs.
Topics: Female; Humans; Human Papillomavirus Viruses; Genotype; Papillomavirus Infections; Sensitivity and Specificity; Molecular Diagnostic Techniques; Papillomaviridae
PubMed: 37284753
DOI: 10.1128/spectrum.00081-23 -
Diagnostic Pathology Mar 2024Oral squamous cell carcinoma in minors is considered to be a distinct entity from OSCC in older patients, with an uncertain etiology. Human papillomavirus (HPV)... (Review)
Review
BACKGROUND
Oral squamous cell carcinoma in minors is considered to be a distinct entity from OSCC in older patients, with an uncertain etiology. Human papillomavirus (HPV) infection may trigger the initiation and promote the progression of OSCC, but these roles have not been firmly established.We aimed to explore the correlation between HPV infection and the development of oral squamous cell carcinoma in minors and know the characteristics of OSCC in young patients more thoroughly.
METHOD
From January 2013 to December 2022,6 cases of OSCC aged < 15 years were selected from the Department of Oral Pathology, Peking University School of Stomatology, Beijing, China. All cases underwent testing for high-risk HPV mRNA infection using the RNA scope technique, and immunohistochemical staining was performed to investigate the expression of p16, pan-cytokeratin (CK), CK5/6, CK7, CK8/18, epidermal growth factor receptor (EGFR), p53, and Ki-67. Furthermore, we reviewed the literature on OSCC in patients aged < 21 years.
CONCLUSIONS
Minors OSCC is associated with HPV infection, and that p16 can serve as an immunohistochemical marker of HPV positivity.
Topics: Humans; Aged; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms; Papillomavirus Infections; Incidence; Papillomaviridae; DNA, Viral; Head and Neck Neoplasms; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 38461286
DOI: 10.1186/s13000-024-01470-9 -
Journal of Virology Jun 2023Even though replication and transcription of human papillomavirus type 16 (HPV16) has been intensively studied, little is known about immediate-early events of the viral...
Even though replication and transcription of human papillomavirus type 16 (HPV16) has been intensively studied, little is known about immediate-early events of the viral life cycle due to the lack of an efficient infection model allowing genetic dissection of viral factors. We employed the recently developed infection model (Bienkowska-Haba M, Luszczek W, Myers JE, Keiffer TR, et al. 2018. PLoS Pathog 14:e1006846) to investigate genome amplification and transcription immediately after infectious delivery of viral genome to nuclei of primary keratinocytes. Using 5-ethynyl-2'-deoxyuridine (EdU) pulse-labeling and highly sensitive fluorescence hybridization, we observed that the HPV16 genome is replicated and amplified in an E1- and E2-dependent manner. Knockout of E1 resulted in failure of the viral genome to replicate and amplify. In contrast, knockout of the E8^E2 repressor led to increased viral genome copy number, confirming previous reports. Genome copy control by E8^E2 was confirmed for differentiation-induced genome amplification. Lack of functional E1 had no effect on transcription from the early promoter, suggesting that viral genome replication is not required for p97 promoter activity. However, infection with an HPV16 mutant virus defective for E2 transcriptional function revealed a requirement of E2 for efficient transcription from the early promoter. In the absence of the E8^E2 protein, early transcript levels are unaltered and even decreased when normalized to genome copy number. Surprisingly, a lack of functional E8^E2 repressor did not affect E8^E2 transcript levels when normalized to genome copy number. These data suggest that the main function of E8^E2 in the viral life cycle is to control genome copy number. It is being assumed that human papillomavirus (HPV) utilizes three different modes of replication during its life cycle: initial amplification during the establishment phase, genome maintenance, and differentiation-induced amplification. However, HPV16 initial amplification was never formally proven due to a lack of an infection model. Using our recently established infection model (Bienkowska-Haba M, Luszczek W, Myers JE, Keiffer TR, et al. 2018. PLoS Pathog 14:e1006846), we demonstrate herein that viral genome is indeed amplified in an E1- and E2-dependent manner. Furthermore, we find that the main function of the viral repressor E8^E2 is to control viral genome copy number. We did not find evidence that it regulates its own promoter in a negative feedback loop. Our data also suggest that the E2 transactivator function is required for stimulation of early promoter activity, which has been debated in the literature. Overall, this report confirms the usefulness of the infection model for studying early events of the HPV life cycle using mutational approaches.
Topics: Humans; Human papillomavirus 16; Oncogene Proteins, Viral; Papillomavirus Infections; Virus Replication; Genome, Viral; NIH 3T3 Cells; Animals; Mice; Cell Line; HEK293 Cells; Viral Transcription
PubMed: 37223953
DOI: 10.1128/jvi.00214-23 -
Infectious Diseases of Poverty Sep 2023The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has...
The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.
Topics: Female; Male; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Vaccination; China
PubMed: 37735709
DOI: 10.1186/s40249-023-01136-6 -
Nutrients Sep 2023Persistent high-risk human papillomavirus (HPV) infection is responsible for most genital, anal, and oropharyngeal cancers, in which men contribute significantly to...
Association between Dietary Vitamin E Intake and Human Papillomavirus Infection among US Adults: A Cross-Sectional Study from National Health and Nutrition Examination Survey.
Persistent high-risk human papillomavirus (HPV) infection is responsible for most genital, anal, and oropharyngeal cancers, in which men contribute significantly to infection and subsequent tumorigenesis in women. Vitamin E has been shown to be associated with vaginal HPV infection and cervical cancer. However, the association of vitamin E consumption with HPV infection among the overall population remains unclear. We investigate the association between vitamin E consumption and genital and oral HPV infection in both men and women. We used cross-sectional data from the National Health and Nutrition Examination Survey between 2013 and 2016 to collect details on their dietary vitamin E intake, genital and oral HPV infection status, and other essential variables. In total, 5809 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 23.7% and 21.1%, respectively. Compared with the lowest vitamin E group Q1 (<5.18 mg/day), the adjusted OR for vitamin E consumption and overall high-risk HPV infection in Q2 (5.18-7.54 mg/day), Q3 (7.55-10.82 mg/day), and Q4 (>10.82 mg/day) were 0.91 (95% CI: 0.81-1.03, = 0.134), 0.77 (95% CI: 0.69-0.87, < 0.001), and 0.72 (95% CI: 0.65-0.80, < 0.001), respectively. Restricted cubic spline regression showed a linear relationship between vitamin E consumption and overall high-risk HPV infection. This linear relationship also existed for vitamin E consumption and overall low-risk HPV infection. After being stratified by gender and site, vitamin E consumption was inversely related to vaginal low- and high-risk HPV infection, penile high-risk HPV infection, and male oral low-risk HPV infection. In conclusion, we identified inverse linear relationships between dietary vitamin E intake and overall high- and low-risk HPV infection. Future well-designed longitudinal studies are still required to validate the impact of vitamin E on HPV carcinogenesis.
Topics: Humans; Adult; Female; Male; Cross-Sectional Studies; Papillomavirus Infections; Human Papillomavirus Viruses; Nutrition Surveys; Diet; Carcinogenesis
PubMed: 37686857
DOI: 10.3390/nu15173825 -
The American Journal of Surgical... Dec 2023Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We...
Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing ( P <0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P <0.001), p53 overexpression (26/42; P <0.001), and hotspot mutations in TP53 (32/42; P <0.001), CDKN2A (26/42; P <0.001) or both (21/42; P =0.003) in the adjacent SCC. Cytoplasmic p16 ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P <0.001) occurred adjacent to verrucous or papillary SCC (17/21; P <0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P <0.004). Undifferentiated p16 ink4a -negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS .
Topics: Male; Female; Humans; Papillomavirus Infections; Tumor Suppressor Protein p53; Human Papillomavirus Viruses; Skin Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Penile Neoplasms; Penis; Papillomaviridae; Class I Phosphatidylinositol 3-Kinases; Vulvar Neoplasms
PubMed: 37768009
DOI: 10.1097/PAS.0000000000002130