Search Results (620)

Human papillomavirus type 53 (HPV53) is one of the most prevalent HPV genotypes in China, frequently detected in cervical intraepithelial neoplasia and cervical cancer, yet remains outside the coverage of all currently available prophylactic vaccines and is relatively understudied. This study performed a comprehensive analysis of HPV53 clinical infection profiles, genomic diversity, and T-cell epitopes to inform therapeutic vaccine development. Clinical analysis of 158 HPV53-positive patients showed that infections were most prevalent in women aged 40–59 years, with persistent infection identified in 13.3% participants and a subset of cases associated with cervical lesions. Genomic analysis of 134 HPV53 isolates identified four lineages (A-D, with lineage D further subdivided into four sublineages, and an overall nucleotide variability of 4.4%. E2 was the most variable protein while E7 was the most conserved. Immunoinformatic prediction identified 176 HLA class I-restricted T-cell epitopes across E6, E7, E1, and E2, from which 20 candidates were selected for experimental validation. Ten demonstrated strong HLA binding affinity in vitro, and murine immunization identified a E6 peptide VYNFAYTDL as an immunodominant epitope. Three validated epitopes exhibited sequence overlap with 12 to 13 of other 13 high-risk HPV genotypes, suggesting their potential as broadly cross-reactive targets. These findings clarify the genomic diversity and immunogenic epitope landscape of HPV53, providing a foundation for the rational design of therapeutic vaccines. Full article

Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article

Introduction: Inequities in access to medicines persist for asylum seekers, refugees, and undocumented migrants in Europe. For vaccines, access gaps not only exist for these groups in childhood routine immunization, but also for life-course and catch-up vaccinations. As part of a broader project examining access to medicines and vaccines for migrants across all stages of the migration cycle, this scoping review synthesizes evidence on the determinants of access to vaccines. Methods: We conducted a scoping review across PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews, Scopus, and grey literature sources, covering the period 2000–2024. Sources were eligible if they addressed access to vaccines among migrants. We examined access to vaccines along the life course, and across phases of the migratory cycle, including departure, transit, reception and settlement, and return or deportation. Results: A total of 47 research studies and grey literature reports were included. Most studies focused on migrants in reception and settlement (destination) settings, with only twelve sources addressing other phases of the migratory cycle. Across European countries, migrants were frequently reported to have lower uptake of routine vaccines (e.g., measles–mumps–rubella (MMR), polio, diphtheria–tetanus–pertussis (DTP), and human papillomavirus (HPV)) and COVID-19 vaccines than host populations. The most frequently reported barriers were related to migrants’ legal status, administrative requirements, and lack of documentation, alongside poor affordability of vaccination, limited awareness of their rights, and mistrust in the health system. Conclusions: Health systems need to adopt innovative approaches to expand vaccine access for migrant populations. Further, protecting confidentiality is essential for building trust and reducing ethical and legal risks. Flexible and coordinated vaccination strategies are required to address migrants’ mobility across the different migration stages and settings. Our findings appeal for sustained improvements in access to vaccines among migrants in Europe, contingent on strong policy commitments to equity, data protection, and the adoption of life-course and catch-up vaccination strategies. Full article

The continuous expression of HPV oncogenes E6 and E7 contributes to the maintenance of the cervical cancer (CC) phenotype by altering gene expression programs involved in tumor progression and aggressiveness. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression in CC, including miR-218-5p, which has been described as a tumor suppressor. In this study, we investigated the impact of HPV-16 oncoproteins E6 and E7 on the regulation of miR-218-5p expression and its target gene PIK3C2A, as well as their functional and clinical relevance in CC. We found that miR-218-5p expression is significantly reduced in HPV-16-positive CC cell lines, while PIK3C2A expression is increased. Silencing the expression of the E6/E7 oncogenes in Ca Ski cells restored miR-218-5p levels and reduced PIK3C2A expression. Conversely, overexpression of the E6 and E7 oncogenes in C-33 A cells significantly decreased miR-218-5p expression and increased PIK3C2A expression. Functional assays performed on C-33 A cells expressing E6 and E7 revealed that ectopic expression of miR-218-5p suppresses cell proliferation and migration, effects that are partially mediated by PIK3C2A. Bioinformatics analysis showed that low miR-218-5p expression and high PIK3C2A expression are associated with reduced overall survival in patients with cervical cancer. Our findings identify the miR-218-5p/PIK3C2A axis as a novel regulatory pathway modulated by HPV-16 oncoproteins E6 and E7 that contributes to CC cell proliferation and migration. Furthermore, miR-218-5p and PIK3C2A emerge as potential prognostic biomarkers in CC. Full article

Human papillomavirus (HPV) has become a leading cause of oropharyngeal cancers, alongside well-known risk factors such as tobacco and alcohol use. Currently, HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) has increased significantly in developed countries, with HPV-16 being the most common high-risk subtype. Clinically, HPV+ OPSCC shows clear differences in prognosis compared to HPV-negative tumors, particularly regarding survival rates and treatment responses. Patients with HPV+ OPSCC tend to have notably better survival outcomes and a more favorable outlook. Strong evidence indicates that HPV-related oropharyngeal cancers represent a distinct epidemiological, clinical, and molecular group, setting them apart from non-HPV-related cancers. As a result, treatment strategies for these subtypes should follow specific clinical protocols to optimize outcomes. Additionally, the viral oncoproteins E6 and E7, which systematically disrupt host tumor-suppressor networks, provide strong reasons for targeted phytotherapeutic interventions. Therefore, there is increasing interest in exploring plant bioactive compounds with promising anti-HPV and anticancer effects that target key oncogenic pathways. This review aims to compile the latest data on bioactive phytochemicals with mechanistic evidence in HPV+ OPSCC, highlight their molecular interactions across oncogenic signaling pathways, and discuss evidence-based findings focusing on research published from 2000 to 2025. Full article

Background: Buparlisib, combined with paclitaxel, improved survival in BERIL-1 trial patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, predictive biomarkers of benefit remain undefined. Objective: To evaluate whether spatial biomarkers extracted from hematoxylin and eosin (H&E) slides using artificial intelligence (AI) can predict overall survival benefit from buparlisib. Methods: Whole-slide H&E images from BERIL-1 trial patients were analyzed using a deep learning model trained to segment tissue compartments and classify cell phenotypes. Three predefined spatial features were evaluated: tumor-infiltrating lymphocyte density, tumor microenvironment heterogeneity, and granulocyte fraction in the tumor invasive margin. Cox proportional hazards model assessed biomarker-treatment interactions. Results: Of 158 trial participants, 144 had available slides. High tumor-infiltrating lymphocyte density (>10%) was associated with significantly improved overall survival with buparlisib versus placebo (HR, 0.25 (95% CI, 0.01–0.64; p = 0.002)), as were high tumor microenvironment heterogeneity (HR, 0.47 (95% CI, 0.27–0.80; p = 0.005)) and granulocyte enrichment in the tumor invasive margin (HR, 0.51 (95% CI, 0.30–0.88; p = 0.01)); within-arm proximity analysis showed higher granulocyte–tumor-cell proximity correlated with improved overall survival on buparlisib (HR, 0.32 (95% CI, 0.18–0.58; p < 0.001)). AI-derived spatial metrics outperformed CD3 immunohistochemistry. Among oropharyngeal tumors, HPV-positive cases were more frequent in patients with high tumor-infiltrating lymphocytes. Conclusions: AI-extracted spatial features from H&E slides were associated with overall survival benefit from buparlisib in R/M HNSCC. These scalable biomarkers support image-based patient selection strategies and are being prospectively evaluated in the BURAN phase 3 trial. Full article

Background: Persistent high-risk human papillomavirus (hrHPV) infection causes over 99% of cervical precancers and cancers worldwide, with HPV genotype 16 (HPV16) responsible for 50% of the cases. Latvia ranks among the top EU countries for cervical cancer incidence and mortality. In the general Latvian population, 4.2% of women are hrHPV-infected, mostly with HPV16. However, information on the circulating HPV16 isolates is missing. Objectives: To study the genomic variability of the Latvian HPV16 isolates, compare them with HPV16 in Europe and across the globe, reveal features associated with the severity of cervical disease and uncover eventual sequence changes due to the national HPV vaccination. Methods: DNA was extracted from the formalin-fixed paraffin-embedded cervical tissues of women diagnosed with cervical intraepithelial neoplasia (CIN) stages I-III and squamous cell carcinoma (SCC) grades 1–3, collected between 2012 and 2024. Samples positive for HPV16 were subjected to whole genome sequencing (WGS) on the Illumina platform (n = 16) or Sanger sequencing of the E6/E7 coding region (n = 31). A consensus HPV16 sequence was generated, and single nucleotide polymorphisms (SNPs) and eventual amino acid substitutions (AAS) were analysed. Results: Complete genomes of 16 HPV16 variants were reconstructed, with 13 related to the European sublineage A1 and 3 to the sublineage A2 references. Sequences showed high conservation; still 93 non-redundant variants were identified. The highest variability was observed for the capsid protein L2, and the lowest, for oncoprotein E7. The prevalence of SNPs and AAS in the Latvian HPV16 variants, specifically in capsid protein L1, did not increase with time, showing no effect of HPV vaccination. Associations between HPV16 sequence features and severity of cervical disease were limited to AAS E6:L90V, which was significantly more common in SCC grade 2/3 than in CINII/III cases (p = 0.015). Conclusions: Highly conserved HPV16 genomes circulating in Latvia harbour a series of unique as well as common nonsynonymous SNPs with respective AAS, with one, AAS E6:L90V, associating with disease severity. No HPV vaccine escape variants were detected. Deciphering complete genomes of HPV16 from CIN and SCC cases in Latvia informs public authorities performing HPV vaccination and is useful for the management of HPV-associated cervical diseases. Full article

The clinical translation of automated HPV detection in Whole Slide Images (WSIs) is challenged by staining variability, sparse viral effects, and the biological continuum between cytology and histology. This work presents a fully automated pipeline for binary patch-level classification of HPV-induced lesions on H&E-stained tissue. The core contribution is a domain-adaptive transfer learning strategy: a ResNet50 backbone is pretrained on the SIPaKMeD cervical cytology dataset rather than ImageNet, then fine-tuned on a target histological cohort. Preprocessing includes adaptive tissue segmentation, blur rejection, and Macenko stain normalization to ensure vendor-agnostic inputs. Evaluated using a strict Leave-One-Patient-Out cross-validation on 42 diagnostic specimens, the SIPaKMeD-based initialization significantly outperforms the ImageNet baseline. This approach achieves higher AUC-ROC scores and superior stability across folds, demonstrating that domain-specific pretraining effectively mitigates data scarcity and class imbalance in digital cervical cancer screening. Under a complementary 5-fold patient-level cross-validation covering all 19 patients of the cohort ($\mathrm{133,704}$ patches, 7181 HPV-positive, prevalence $5.37\%$), the SIPaKMeD-pretrained model attains a mean test AUC-ROC of $0.694$ with a $95\%$ patient-aware bootstrap confidence interval of $[0.681, 0.705]$, consistently above the ImageNet baseline mean of $0.656$ obtained on the controlled three-fold ablation. Full article

Background: Effective triage of HPV DNA-positive women is needed to reduce unnecessary colposcopies while maintaining cervical cancer prevention. We evaluated genotype-specific 7-type HPV E6/E7 mRNA triage in a real-world screening cohort. Methods: In this population-based single-centre study at the University Hospital of North Norway, 42,791 women underwent primary screening with the cobas HPV DNA assay during the period 2019–2024. Among 2370 HPV DNA-positive women, reflex cytology, 7-type HPV mRNA testing, and an ATHENA-derived triage strategy were compared using histologically confirmed CIN3+ through 31 December 2025 as the endpoint. Results: CIN3+ was detected in 60/2370 women (2.5%). Test positivity was 47.0% for cytology, 54.7% for ATHENA-derived triage, and 33.4% for HPV mRNA. Sensitivity was 78.3%, 86.7%, and 73.3%; specificity was 53.8%, 46.1%, and 67.7%; and PPV was 4.2%, 4.0%, and 5.6%, respectively. Colposcopies per CIN3+ detected were 23.7, 24.9, and 18.0. Conclusions: HPV mRNA triage improved referral precision and colposcopy efficiency, but with lower sensitivity than ATHENA-derived triage. These findings support 7-type HPV mRNA testing as a potentially useful molecular triage option where structured follow-up is feasible. Full article

Cervical cancer remains one of the most lethal cancers affecting women, with infection by high-risk Human Papillomavirus (HR-HPV), especially HPV-16, recognized as a primary cause. Phyllanthus urinaria, a plant that grows in Indonesia, has demonstrated notable both antiviral and anticancer properties. This study aimed to investigate the potential of P. urinaria as both an antiviral and anti-cervical cancer agent. The HPV-16 E6 protein was modeled using homology modelling, with model accuracy verified through torsional angle assessment and identification of conserved regions. Molecular docking was performed to examine E6–p53 interactions. Fraction of n-hexane compounds of P. urinaria were further evaluated for their interaction with E6 by molecular docking and molecular dynamics simulation. Additionally, in vitro cytotoxicity assays were conducted using HaCaT (normal keratinocyte) and HeLa (cervical cancer) cell lines. Compounds from P. urinaria were found to interact with E6 within conserved regions and these interactions were more stable conformationally than those observed for p53. In vitro assay demonstrated that P. urinaria exhibited moderate cytotoxicity against HeLa cells but had limited toxicity toward HaCaT cells. The n-hexane fraction of P. urinaria leaves exhibits anti-cervical cancer activity by inhibiting HPV-16 E6 and eliminating cervical cancer cells. Full article

Oral squamous cell carcinoma (OSCC), comprising ~90% of oral malignancies, remains a major global health burden with rising incidence despite declining tobacco use. While tobacco and alcohol are classic dominant risk factors, a distinct subgroup of nonsmoking, nondrinking (NSND) patients is increasingly recognized, accounting for 15–35% of OSCC cases in many cohorts, particularly in developed countries. This emerging epidemic shows striking demographic patterns: strong female predominance (often 65–77% of cases), bimodal age distribution with peaks in young adults (<45 years) and elderly individuals (>70 years), and overrepresentation among non-Hispanic White and certain Asian populations. Unlike traditional habit-related OSCC, which favors the floor of the mouth in older males, NSND tumors predominantly arise on the lateral tongue, gingiva, and buccal mucosa. Etiopathogenesis extends far beyond conventional carcinogens and involves multifactorial mechanisms, including chronic mechanical irritation from dental factors, oral microbiome dysbiosis enriched with periodontal pathogens (e.g., Fusobacterium nucleatum and Porphyromonas gingivalis), limited roles for viruses (minimal HPV contribution, possible EBV or “hit-and-run” HSV effects), genetic susceptibilities (e.g., Fanconi anemia and CDKN2A mutations), epigenetic changes, hormonal influences contributing to female bias, metabolic conditions (diabetes and hyperlipidemia), poor oral hygiene, and chronic inflammation. NSND OSCC frequently exhibits a distinct immunological profile with higher tumor-infiltrating lymphocytes and PD-L1 expression, potentially favoring immunotherapy, though prognosis remains heterogeneous—better in some cohorts due to fewer comorbidities, yet worse in young patients with higher recurrence and second primary tumor risks. Delayed diagnosis is common due to low suspicion in “low-risk” individuals. This review underscores NSND OSCC as a unique entity requiring expanded risk assessment, heightened clinical vigilance for persistent oral lesions regardless of habit history, and targeted research into novel prevention and therapeutic strategies. Full article

Background/Objectives: Human papillomavirus (HPV) vaccination coverage among adolescents remains below public health targets despite strong evidence of vaccine effectiveness in preventing HPV-related cancers. Digital interventions (e.g., serious games) may improve HPV vaccine uptake, but evidence for effects on vaccination behavior remains limited. Methods: This secondary analysis of a randomized controlled trial evaluated a co-designed, game-based digital intervention to increase HPV vaccine initiation among unvaccinated youth aged 11–14 years and their parents. The sample included 64 parent–adolescent dyads (33 intervention and 31 usual care dyads). The primary outcome was HPV vaccine initiation at 2-month follow-up. Results: A significantly greater proportion of adolescents in the intervention group initiated HPV vaccination compared with controls (88.5% vs. 46.2%; χ²(1) = 10.58, p = 0.001; risk difference = 0.423, 95% CI = [0.196, 0.650]). No significant between-group baseline differences were observed in parent HPV vaccination intention, knowledge, or psychosocial perceptions, although adolescent vaccination intention was higher in the intervention group. In adjusted logistic regression controlling for adolescent baseline HPV vaccination intention, intervention participants remained significantly more likely to initiate vaccination than controls (OR = 9.31, 95% CI = 2.13–40.70, p = 0.003). Intervention acceptability was high, with most parents and adolescents reporting that the game was easy to use, engaging, and relevant to vaccination decision-making. Conclusions: These findings provide preliminary evidence that a brief, family-centered, game-based digital intervention may help increase HPV vaccination initiation among adolescents. Larger trials with longer follow-up are needed to assess vaccine series completion and effectiveness across diverse settings. Full article

Background: Human papillomavirus (HPV) is a serious infection which is primarily transmitted through sexual intercourse. Almost 100% of cervical cancers are caused by HPV. Limited awareness of HPV leads to delayed cancer diagnoses, significantly increasing mortality and morbidity rates. Aim: The purpose of this study was to develop strategies to increase awareness of human papillomavirus screening and vaccination among women in Limpopo Province, South Africa. Setting: This study was carried out in the Vhembe District of the Thulamela Municipality of Limpopo Province. Methods: The E-Delphi method was used, and the researcher used a quantitative approach. A total population of 15 nursing managers was part of the study. Questionnaires were used to collect data. Data were analysed using the statistical package for the social sciences version 26. Results: In Round 1, 8 (53.3%) of the 15 participants strongly supported the strategy of updating women with the most recently revised HPV screening guidelines. In Round 2, consensus was achieved, with 14 (93.3%) of the participants strongly agreeing that the development of teaching programmes in healthcare facilities is necessary. This indicates a strong convergence of expert opinion on the importance of structured educational interventions to support the implementation of the strategy. The consensus in this study was defined as ≥70% agreement between participants on each item. Conclusions: The lack of awareness of HPV is concerning because early detection and treatment can prevent serious health problems. The study used the E-Delphi method to assess the effectiveness of strategies to increase awareness of HPV screening and vaccination in women. Contribution: Health policy initiatives may improve public awareness of HPV and vaccination, especially by focusing on educating nurses, which could improve women’s awareness and encourage HPV screening and vaccination. Full article

Background: HPV16 is the most prevalent high-risk genotype associated with cervical cancer, yet the genetic variability and immune potential of the replication protein E1 are less characterized in asymptomatic infections. We assessed HPV16 E1 diversity and predicted conserved T-cell epitopes. Methods: We conducted a descriptive cross-sectional study of cervical samples from women undergoing HPV screening. HPV was detected with universal primers and then HPV16-specific PCR. Thirty HPV16-positive samples underwent full-length E1 amplification and nanopore amplicon sequencing. Variability and phylogeny were analyzed with Clustal Omega and MEGA (maximum likelihood). MHC class I and II epitopes were predicted with the IEDB using HLA alleles representative of South American populations and evaluated for conservation, toxicity, allergenicity, and population coverage. Results: Mutations were detected in 14/30 samples, while 16 sequences matched the reference (GenBank: NC_001526.3). European lineages (A1–A3) predominated, with one sequence in the Asian-American lineage D. Seven highly conserved MHC I epitopes and 37 conserved MHC II epitopes were identified. Epitopes mapped to multiple regions across the E1 sequence. Predicted global coverage was 94.38% for MHC I, 83.75% for MHC II, and 99.09% combined. Conclusions: HPV16 E1 is highly conserved and contains candidate T-cell targets with broad predicted coverage, supporting evaluation for future vaccine or immunotherapy strategies. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) remains a global public health challenge with significant morbidity and mortality. Emerging epidemiological data indicate a rising global incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Serology for early HPV antigens has been highlighted as a relevant biomarker for HPV-associated OPSCC. This study aimed to determine the seroprevalence of HPV16 E6 antibodies in HNSCC patients in the state of Espírito Santo, Brazil. Methods: This is a prospective longitudinal cohort study in which 287 patients with HNSCC were enrolled, recruited from two oncology centers in Espírito Santo between 2011 and 2018, along with 68 cancer-free individuals. Serum samples were analyzed using the HPV16 E6 GST Capture ELISA assay. Statistical analysis was performed using SPSS. Binary logistic regression was employed to identify independent predictors of seropositivity. Results: The overall seroprevalence of HPV16 E6 antibodies was 7.3%. Seropositivity was observed in tumors of the oral cavity (6.2%) and oropharynx (13.3%). Patients with OPSCC demonstrated a significantly higher likelihood of seropositivity compared to those with tumors of the oral cavity, larynx, and hypopharynx (OR = 2.96, 95% CI: 1.21–7.28, p = 0.018). The highest frequency of HPV16 E6-positive cases occurred in tumors of the palatine tonsils (OR = 6.00; 95% CI: 1.58–22.89; p < 0.009). No seropositive cases were observed in hypopharyngeal or laryngeal tumors. Among patients with OPSCC and oral cavity squamous cell carcinoma (OCSCC), HPV16 E6 serostatus did not significantly correlate with sociodemographic, behavioral, or clinical tumor characteristics. Conclusions: Our findings reinforce the predilection of HPV-associated carcinogenesis for the oropharynx, more specifically in the palatine tonsils. In addition, this study highlights HPV16 E6 serology as a potential biomarker for HPV-driven OPSCC and underscores Brazil’s epidemiological heterogeneity, warranting standardized clinical validation. Full article