Search Results (293)

Background/Objectives: Cervical cancer, predominantly driven by persistent infection with high-risk human papillomaviruses (HPVs), is one of the most common malignancies and an important cause of cancer-related mortality among women worldwide. Although existing licensed prophylactic HPV vaccines confer excellent protection, their global use remains suboptimal due to concentrated manufacturing capacity and high production costs. This study aimed to establish a cost-effective multivalent HPV virus-like particle (VLP) vaccine platform. Specifically, we used an enhanced baculovirus expression vector system to produce a 12-valent HPV VLP vaccine to improve antigen yield, thereby reducing manufacturing costs and ultimately improving affordability and availability in low- and middle-income countries. Methods: Optimized expression cassettes and an insect cell culture process were designed to enhance productivity across 12 HPV L1 genotypes. A scalable purification scheme integrating ion-exchange and adsorption chromatography was developed to produce high-purity VLPs with consistent structural integrity. Immunogenicity was assessed in a murine model. Elicited HPV type-specific IgG antibody responses were compared with those induced by the licensed 9-valent HPV vaccine. Results: The assembled 12-valent VLPs were comprehensively characterized using biophysical and immunochemical analyses, confirming structural stability and correct antigenicity. In vivo immunogenicity studies in mice showed strong and serotype-specific IgG responses, comparable or superior to those induced by the licensed 9-valent commercial vaccine. Conclusions: The enhanced baculovirus expression vector system is a versatile and economically sustainable platform for next-generation HPV vaccine production. This technology offers a promising approach to lowering vaccine manufacturing costs and improving global access, particularly in low- and middle-income regions heavily burdened by HPV-associated diseases. Full article

Background/Objectives: Human papillomaviruses (HPVs) are the most common sexually transmitted viruses worldwide and are strongly associated with multiple cancers, including cervical cancer. In France, HPV prevention relies on a combination of organized cervical cancer screening and prophylactic vaccination; however, coverage remains below international targets. Methods: This narrative review summarizes recent advances in HPV prevention in France, with a focus on screening strategies, including the integration of high-risk HPV testing and vaginal self-sampling, as well as vaccination policies that now include both girls and boys, notably through school-based programs. Results: International comparisons, particularly with Australia and several European countries, are used to highlight successful strategies and transferable lessons that could enhance the effectiveness of French prevention efforts. The review also discusses persistent barriers to uptake, including social, organizational, and cultural factors, and considers opportunities to reduce inequalities in access to prevention. Conclusions: Overall, this work provides a comprehensive overview of the current landscape of HPV prevention in France and situates national efforts within a global public health context, offering insights for policy development and future research directions. Full article

Cutaneous papillomaviruses (PVs) are host-specific DNA viruses that cause papillomas in many wild cervids, including red deer, moose, roe deer, white-tailed deer, and reindeer. Species-specific PVs such as CePV1 and AaPV1 typically induce rough, verrucous skin and mucosal lesions that, while usually benign, can impair feeding, movement, vision, or mating. A high prevalence—especially in young or immunocompromised animals—may affect population health. Transmission occurs through contact, skin microtrauma, or possibly ectoparasites. PV lesions can resemble more serious diseases, complicating diagnostics. Understanding PV diversity and ecology is important for wildlife health monitoring, conservation planning, and assessing cross-species transmission risks. Full article

Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus–host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology. Full article

Background: Vaccination against human papillomaviruses (HPVs) and cervical cancer screening represent effective tools for preventing this neoplasia, but access to health services is limited for vulnerable women. We investigated prevalence of high-risk HPV and abnormal cervical cytology, as well as knowledge about HPV and the HPV vaccine, among homeless and migrant women in Rome, Italy. Methods: Cytologic samples in PreservCyt (Hologic) were employed for liquid-based cytology (ThinPrep Processor 5000, Hologic) and high-risk HPV DNA testing (Xpert HPV assay, Cepheid). Socio-demographic data, anamnestic, and behavioral data were retrieved from electronic archives. A questionnaire was employed to assess knowledge about HPV and HPV vaccination. Results: A total of 134 women were included (median age: 43 years; interquartile range, IQR: 34–50), mostly coming from Central–South America (69, 51.5%). Of the 127 cytologic specimens collected, one (0.8%) was invalid for the HPV test and five (3.9%) were unsatisfactory for the morphological evaluation. High-risk HPV positivity was found in 18 women of the 126 women with a valid HPV test (14.3%). A total of 10 women of the 122 women with an adequate cytology (8.2%) had abnormal cytology. Overall, 57/134 women (42.6%) had never heard of HPV or were unsure about it. Only 29 of the 77 women who had heard of HPV (37.7%) knew of the HPV vaccine, and only 2 had been vaccinated in the entire study group (1.5%). Conclusions: Tailored preventive strategies and comprehensive information campaigns should be developed and implemented to enhance awareness of HPV infection and actively promote vaccination among women in vulnerable groups. Full article

Evidence on the contribution of human papillomaviruses (HPVs) to the development of esophageal papillomas is still controversial. Esophageal papillomatosis (EP) is considered an exceedingly rare, but distinct entity within esophageal proliferations, with about 57 cases published so far. Tissues derived from an EP case and from non-EP esophageal papillomas were investigated for the presence of HPVs and virus-positive specimens were subsequently analyzed for transcriptional activity and surrogate markers of infection. Low-risk type HPV6 DNA was detected in a subset of the esophageal papillomatous tissues, including EP, and a variant isolate belonging to lineage A. In the EP tissue, the abundant expression of the viral E6/E7 mRNA and the presence of HPV6-specific E1^E4 transcripts, the latter indicative of productive viral infection, were detected. An analysis of HPV-specific neutralizing antibodies in sera obtained from the EP case during natural infection as well as after HPV vaccination revealed that, despite extensive manifestation, HPV6-specific antibodies were absent during natural infection and only elicited after repeated HPV immunizations. Although limited by a small sample size, this exploratory study suggests a possible involvement of HPV6 in the development of EP. Furthermore, this study may contribute to the evidence distinguishing EP from less extensive forms of non-EP esophageal squamous papillomas. Full article

Background and Objectives: Kidney transplant recipients (KTRs) face increased susceptibility to persistent viral infections due to prolonged immunosuppression. While high-risk human papillomavirus (HR-HPV) infection is known to be more prevalent in this population, little is known about the co-occurrence of HPV with human herpesviruses (HHVs) infection in the female genital tract. This study aimed to investigate the presence, dynamics, and potential interactions between HR-HPV and HHVs infections—including HSV-1, HSV-2, EBV, CMV, HHV-6, and HHV-7—in female KTRs during the first year after transplantation. Materials and Methods: A total of 39 female KTRs and 79 age-matched healthy controls were enrolled in the study. Cervicovaginal swabs from recipients were obtained at three time points: two weeks, six months, and one year post-transplantation. HPV DNA was screened using PCR, followed by high-risk HPV genotyping and quantitative viral load assessment using two commercial PCR kits. HHVs were detected using a multiplex PCR assay. Results: HPV DNA was detected in 98% of the KTRs at least once during follow-up, which was significantly greater than in the controls (38%). HR-HPV was identified in 46% of the recipients over the study period, with the highest viral load at one year post-transplantation. HHVs were detected in 72% of the KTRs but not in 43% of the controls (p < 0.01), with EBV and CMV being the most common. Coinfection with HR-HPV and HHVs occurred in 46% of the recipients but not in the controls. Samples containing both EBV and CMV had significantly higher HR-HPV viral loads than samples with no HHVs or with single/other HHV combinations (p < 0.01). All cervical intraepithelial neoplasia patients were found to have combined HPV and HHV infection. Conclusions: Female KTRs present a high burden of both HR-HPV and herpesviruses infections, with increased HPV viral loads. These findings suggest a potential synergistic interaction between HR-HPV and herpesviruses in the immunosuppressed setting. Full article

Oncogenic viruses are well-established contributors to cancer development in both humans and animals. While many animal oncogenic viruses exhibit strong host specificity, concerns remain about their potential to cross species barriers and impact human health. This article examines the classification and molecular mechanisms of oncogenic viruses, including retroviruses, papillomaviruses, herpesviruses, and hepadnaviruses, in animals. It explores historical cases of cross-species transmission, such as the contamination of early polio vaccines with simian virus 40 (SV40), which resulted from the use of rhesus monkey kidney cells and insufficient screening for latent simian viruses, and the hypothesised association between bovine leukaemia virus (BLV) and human breast cancer. To provide a broader comparative perspective, the discussion also includes examples of viruses with a lower economic impact, illustrating that zoonotic and oncogenic potential is not limited to commercially significant species. Biological barriers—including receptor specificity and immune defences—generally limit transmission; however, frequent human–animal interactions, consumption of contaminated food, and viral mutations may increase zoonotic risk. Advances in molecular diagnostics, such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and serological testing, play a critical role in identifying emerging threats. Prevention strategies, including veterinary vaccination programs, biosafety protocols, and the One Health approach integrating human and veterinary medicine, are essential for mitigating risks. While current evidence indicates that oncogenic animal viruses do not significantly contribute to human cancers, ongoing surveillance and research remain crucial to detect emerging threats. Understanding viral oncogenesis in animals continues to provide valuable insights into cancer prevention and therapy in humans. Full article

High-risk human papillomaviruses (HPVs), particularly types 16 and 18, drive carcinogenesis by rewiring host metabolism and mitochondrial function. The oncoproteins E5, E6, and E7 collectively induce mitochondrial fragmentation, increase reactive oxygen species (ROS), and promote a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis (the Warburg effect). A redox-sensitive mitochondrial protein, Reactive Oxygen Species Modulator 1 (ROMO1), has emerged as a key mediator of these processes. ROMO1 contributes to mitochondrial morphology, regulates ROS homeostasis, and interacts with key stress-response pathways. While ROMO1 is overexpressed in many cancers and correlates with poor prognosis, recent data suggest that HPV-associated cervical lesions exhibit a unique biphasic expression pattern, with high ROMO1 levels in early stages and reduced expression in advanced tumors. The underlying molecular mechanisms remain unclear, but may involve HPV genome integration, NF-κB suppression, or epigenetic silencing. Key mechanisms such as how HPV modulates ROMO1 expression and how this contributes to stage-dependent metabolic vulnerability remain incompletely understood. This review highlights the current understanding of how HPV oncoproteins impact mitochondrial structure and function, emphasizes the role of ROMO1 in this context, and compares findings with other cancer types. Although no ROMO1-targeted therapies currently exist, the protein may serve as a redox-sensitive biomarker and potential vulnerability in HPV-driven tumors. We propose that targeting mitochondrial fragmentation, ROS signaling, or metabolic reprogramming may offer new avenues for therapeutic intervention. Further research is needed to clarify ROMO1’s dual role in early vs. late-stage disease and to validate its relevance as a clinical target. Our review fills a gap in the current literature by being the first to systematically explore ROMO1’s contribution to HPV-induced mitochondrial dysfunction and metabolic rewiring, and we outline research priorities for future studies. Full article

Background/Objectives: To assess overall and type-specific HPV vaccine effectiveness in central and eastern Europe (CEE), the age-stratified prevalence of cervical HPV infection was determined among Slovenian women aged 20 to 64 attending a cervical cancer screening program 14 years after implementation of a national HPV vaccination program, which was then compared with 2009–2010 pre-vaccination data using the same methodological approach. Methods: Cervical samples of 4419 women were tested in 2023–2025 using the clinically validated Alinity m HR HPV Assay, and individual HPV types were determined by the Allplex HPV HR Detection assay. Results were compared with 2009–2010 pre-vaccination data generated using the same assay on an age-range matched cohort of women. Results: The overall prevalence of the 14 Alinity-targeted HPV types was 10.0% in 2023–2025 versus 13.3% in 2009–2010 (p < 0.001). HPV16 prevalence declined from 3.5% to 1.5% (p < 0.001), and HPV18 prevalence from 1.1% to 0.5% (p = 0.005). In women aged 20 to 24 with 40% uptake of quadrivalent HPV vaccine, overall HPV prevalence dropped from 25.3% to 12.8% (p < 0.001). No single case of HPV16/HPV18 infection was detected among vaccinated women. Conclusions: The first large-scale, systematic, and methodologically consistent study of HPV vaccine effectiveness in CEE showed a substantial reduction in high-risk HPV prevalence after implementation of the national program, with the greatest decline among women aged 20 to 24, who harbored the highest HPV burden in the pre-vaccination era. These locally acquired data will considerably inform public health strategies on cervical cancer elimination in CEE. Full article

Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using ¹H nuclear magnetic resonance spectroscopy (¹H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1α. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16. Full article

Organ transplantation significantly enhances the survival and quality of life for recipients. However, multiple dependent and independent variables can adversely affect life expectancy after transplantation. Cancer is one of the most common causes of morbidity and mortality for long-term organ transplant recipients. The incidence of cancer in transplanted tissues can be twice as high in approximately 32 distinct cancer types. Oncogenic viruses present in graft tissues may contribute to the etiology of various cancers in transplant recipients. Such oncogenic viruses include hepatitis viruses, papillomaviruses, Epstein–Barr virus, Kaposi’s sarcoma, Merkel cell virus, JC virus, BK virus, and human T-lymphotropic virus type 1, all of which have been associated with various malignancies in these patients. To mitigate this risk, a comprehensive viral screening protocol should be integrated into the transplantation process. Depending on the type of graft, diagnostic methods, control strategies, and post-transplantation care may vary considerably. To efficiently implement any strategy to inhibit viral oncogenicity, a comprehensive understanding of viral–host interactions involving oncogenic viruses within graft tissue is essential. The current view of tumor biology is that changes in the tumor microenvironment and immune signaling influence evolutionary selection pressures. Such interactions ultimately promote conditions that favor uncontrolled host–cell proliferation and malignant transformation. This review examines these viral–host interactions and their role in cancer development among transplant recipients. Full article

Background/Objectives: Cervical cancer (CC), a highly prevalent female neoplasia, has been prevented through repeated cervicovaginal cytology, the so-called Pap test, across women’s lifespans. The now undebatable role of Human Papillomaviruses in the etiology of CC and the development of high-throughput automated molecular amplification diagnostic platforms is allowing for the replacement of the Pap test with HPV testing. The objective of this review is to contextualize the current strategies for cervical cancer screening using molecular assays. Methods: The many existing screening tools relying on molecular markers and their advantages and drawbacks are discussed. Results: Testing for oncogenic Human Papillomavirus DNA is presently the mainstay strategy for molecular screening, replacing cervicovaginal cytology. Conclusions: The presence of HPV-DNA is the most sensitive marker for cervical cancer and its precursor lesions. However, its adoption has led to an increase in the number of screening-positive subjects, generating extra demand for triage resources. New algorithms and technologies are fast being developed to address this need, moving toward risk-based management. Full article

Mouse papillomavirus (MmuPV1) is the first papillomavirus known to infect laboratory mice, making it an irreplaceable tool for research on papillomaviruses. Despite wide use, standardized techniques for conducting MmuPV1 animal research are lacking. In this report, we describe an unexpected MmuPV1 outbreak causing recurrent papillomatosis in a specific pathogen-free animal research facility. The infected mice displayed characteristic papillomatosis lesions from the muzzles, tails, and feet with histological signs including anisocytosis, epithelial dysplasia, and typical koilocytosis. Etiology studies showed that the papilloma tissues exhibited MmuPV1 infection with expression of viral early and late genes detected by RNA-ISH using MmuPV1 antisense probe to viral E6E7 region and antisense probe to viral L1 region. The viral L1 protein was detected by an anti-MmuPV1 L1 antibody. PCR amplification and cloning of the entire viral genome showed that the origin of the outbreak virus, named MmuPV1 Bethesda strain (GenBank Acc. No. PX123224), could be traced to the MmuPV1 virus previously used in studies at the same facility. Our data indicate that MmuPV1 could exist in a contaminated environment for a long period of time, and a standardized international animal protocol discussing how to handle MmuPV1 studies is urgently needed. Full article

Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) remain scarce. This study investigated CPV types present in oral and cutaneous papillomatous lesions in domiciled dogs from Acre and Rondônia States, Brazil. Sixty-one dogs with macroscopically consistent lesions were clinically evaluated, and tissue samples were collected for histopathological examination and PCR targeting the L1 gene. Among these, 37% were histologically diagnosed as squamous papillomas or fibropapillomas, and 49.2% (30/61) tested positive for papillomavirus DNA. Sequencing of the L1 gene revealed that most positive samples belonged to CPV1 (Lambdapapillomavirus 2), while one case was identified as CPV8 (Chipapillomavirus 3). Complete genomes of three CPV1 strains were obtained via high-throughput sequencing and showed high identity with CPV1 strains from other Brazilian regions. Phylogenetic analysis confirmed close genetic relationships among isolates across distinct geographic areas. These findings demonstrate the circulation of genetically conserved CPVs in the Amazon and reinforce the value of molecular and histopathological approaches for the accurate diagnosis and surveillance of viral diseases in domestic dogs, especially in ecologically complex regions. Full article