Search Results (54)

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

Human papillomavirus (HPV) is a recognized oncogenic agent in several epithelial malignancies, though its role in esophageal squamous lesions remains unclear. Esophageal squamous papilloma and papillomatosis are rare, often benign lesions, but increasing evidence suggests possible associations with high-risk HPV genotypes and a non-negligible risk of dysplasia and malignant transformation. This narrative review summarizes current evidence on epidemiology, clinical features, histopathology, and diagnostic approaches, emphasizing advanced endoscopic imaging techniques that improve lesion detection and characterization. Management relies primarily on complete endoscopic resection with histological and virological evaluation. While small, non-dysplastic solitary lesions may not require routine surveillance, multifocal or high-risk HPV-positive cases warrant closer follow-up. Standardized HPV testing and long-term prospective studies are needed to better define the oncogenic potential and inform surveillance and treatment strategies. Full article

Bovine papillomatosis, caused by a growing group of bovine papillomaviruses (BPVs), is a disease with benign proliferative lesions (papillomas) that may progress to malignancies due to immunological, environmental, or viral factors. This study investigated BPV type diversity in cattle from the Province Santo Domingo de Tsáchilas in Ecuador. Warty lesions were collected from 30 cattle across eight farms. Nucleic acids were extracted using a silicon dioxide-based method, and the partial L1 gene was amplified with PCR. DNA sequences were analyzed using maximum likelihood phylogenetics. Fifty-seven warty lesions yielded ten well-known BPV types: BPV1, BPV2, BPV4, BPV6, BPV8, BPV9, BPV10, BPV13, BPV14, and BPV42. Recently described viral types, BPV-CR2 from Costa Rica and BPV/BR-UEL08 from Brazil, were also detected, alongside a putative novel viral type, BPVEC2024-6-22.1—likely belonging to the genus Xipapillomavirus. This genus had the highest overall count. In contrast, Deltapapillomaviruses were found across all sampled farms. This study underscores BPV diversity in this localized region of Ecuador, and includes genotypes linked to cancers such as enzootic hematuria. The findings provide important epidemiological insights, contributing to vaccine development or immune therapy and improved disease management. Full article

Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition and expression of the immune checkpoints programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in RRP. We analyzed tissue samples from 30 patients treated at a tertiary care center between 2009 and 2021, including paired samples from individual patients collected at different time points. Immunohistochemical staining was performed for CD4, CD8, CTLA-4, FoxP3, and PD-L1 and correlated with disease severity and previous adjuvant therapies. Overall disease burden and intervention-free survival were not associated with the abundance of CD4⁺, CD8⁺, or FoxP3⁺ T cells, nor with immune checkpoint expression. However, patients with aggressive disease exhibited a higher intralesional FoxP3/CD4 T-cell ratio. Prior intralesional cidofovir treatment was associated with reduced CD4⁺ T-cell infiltration. These findings suggest that a locally immunosuppressive microenvironment, reflected by an elevated FoxP3/CD4 ratio, contributes to disease severity in RRP. Consistent CTLA-4 expression across all evaluated samples supports further investigation of anti-CTLA-4 therapy, either alone or in combination with other checkpoint inhibitors. Full article

Bovine papillomaviruses (BPVs) have been widely characterized from cutaneous warts in cattle worldwide. However, there are still limited studies addressing the geographic distribution of viral types and their potential associations with the histopathological characteristics of lesions, particularly in the vast and ecologically diverse Amazon region. This study aimed to histologically and phylogenetically characterize cutaneous papillomatous lesions in cattle from the Vale do Guaporé, located in the Brazilian Western Amazon. A total of 54 wart samples were collected from 44 cattle clinically diagnosed with cutaneous papillomatosis. Histopathological analysis classified 58.33% of cases as fibropapillomas and 39.58% as squamous papillomas. Molecular analysis, based on L1 gene amplification and sequencing, identified the presence of previously reported BPV types (BPV2, 4, 5, 12, 13, and 15), along with a novel BPV14 subtype and three putative new types (PNT). Statistical analysis revealed that BPV2 was significantly associated with fibropapillomas (p = 0.023), whereas BPV13 was linked to cauliflower-like morphological lesions (p = 0.008). These findings enhance the understanding of BPV diversity circulating in cattle from the Amazon region and provide valuable insights into the clinicopathological aspects of bovine cutaneous papillomatosis, which may aid in future epidemiological surveillance and disease control strategies. Full article

Background: Human Papillomavirus (HPV) is a predominant and clinically significant virus affecting individuals of all ages, including children and adolescents. Despite its well-documented role in adult health, particularly in cervical cancer, HPV’s impact on younger populations still remains underexplored. Methods: This review investigates the epidemiology, clinical manifestations, transmission pathways, and historical context of HPV in children and adolescents. Results: The study demonstrates a significant prevalence of HPV DNA within paediatric populations, with diverse clinical manifestations such as verruca vulgaris, anogenital warts, and Juvenile Recurrent Respiratory Papillomatosis, alongside substantiating vertical transmission from mother to infant. We also highlight ground-breaking research milestones, including improvements in genetic studies, the development of HPV vaccines, and ongoing investigations into infection dynamics, and long-term health outcomes. Conclusions: By synthesising existing knowledge, this review aims to enhance clinical decision-making, improve management strategies, and pave the way for future research in HPV-related paediatric diseases. Full article

Laryngeal papillomatosis and recurrent respiratory papillomatosis are caused by the human papillomavirus. It is characterized by papillomatous growths and is the most common benign disease of the larynx. Juvenile-onset RRP is characterized by more aggressive disease compared with adult-onset RRP. Patients often require frequent surgical procedures, with an increasing shift toward office-based treatment. A variety of surgical and adjuvant medical therapies are available with mixed responses. New targeted therapies and vaccines are currently under investigation as potential adjuncts in the management. Full article

Background: Recurrent respiratory papillomatosis (RRP) is a rare, non-malignant disease caused by human papillomavirus (HPV) types 6 and 11. The condition primarily affects the larynx, potentially leading to life-threatening airway obstruction. It is more aggressive in younger patients, necessitating frequent surgical interventions. This study investigates the therapeutic potential of the prophylactic HPV vaccine Gardasil^® in RRP patients, focusing on its impact on lesion size and the frequency of surgical interventions. Furthermore, a literature review was conducted to analyze the factors influencing the decision to vaccinate. Methods: A retrospective analysis was conducted on 63 RRP patients treated from 2008 to 2021. Disease burden was assessed using the Derkay score and the annual frequency of laser-surgical ablations. Comparisons were made between pre- and post-vaccination periods in vaccinated patients (n = 18), and between first and second halves of the disease’s course in unvaccinated patients (n = 14). Results: A reduction in the frequency of surgical interventions post-vaccination (p < 0.05) could be seen. The cumulated Derkay score per year decreased after second and third vaccination (p < 0.05). The decision to be vaccinated is influenced by multiple factors (e.g., potential side-effects, sociocultural factors, impact of social media, pre-existing conditions and the wider context of the recent pandemic). Conclusions: Gardasil^® appears to reduce the frequency of surgery and lessen disease severity in RRP patients, supporting the potential role of HPV vaccination as a therapeutic option for RRP. Moreover, it is crucial to overcome skepticism towards vaccinations to prevent the development of HPV-associated diseases in the first place. Full article

Objective: This study assesses the associations between dendritic cells, HPV 6 and 11, and Recurrent Respiratory Papillomatosis (RRP) aggressiveness. Methods: The Derkay score was calculated using information obtained from the medical records. Biopsies from 36 patients with juvenile RRP (JRRP) and 43 adult RRP (ARRP) patients were analyzed under light microscopy, and their clinical data were collected. Immunohistochemical analysis using antibodies against CD83, CD1a, Factor XIIIa, and S100 was performed, and inflammatory cells were quantified. Data obtained were analyzed using the chi-squared test, in addition to the Mann–Whitney and Z tests for two proportions, considering a confidence interval of 95% and p < 0.05 as statistically significant. Results: A higher quantity of S100 was identified in the epithelium (p < 0.001) and in the conjunctive tissue (p = 0.027) among the ARRP cases, while CD83 (p = 0.025) and Factor XIIIa (p = 0.018), both in the epithelium, were identified among the JRRP cases. We observed significant association between a higher quantity of CD83 in the epithelium in the juvenile group with a low Derkay index (p = 0.034) and with HPV 6 (p = 0.039). Conclusions: An increased quantity of dendritic cells is present in individuals diagnosed with RRP, regardless of age, and this may be related to the lower Derkay index, regardless of the HPV type detected. Full article

This study investigates the efficacy of various genomic prediction models—Genomic Best Linear Unbiased Prediction (GBLUP), Random Forest (RF), Support Vector Machine (SVM), Extreme Gradient Boosting (XGB), and Multilayer Perceptron (MLP)—in predicting genomic breeding values (gEBVs). The phenotypic data include three binary health traits (anodontia, distichiasis, oral papillomatosis) and one behavioral trait (distraction) in a population of guide dogs. These traits impact the potential for success in guide dogs and are therefore routinely characterized but were chosen based on differences in heritability and case counts specifically to assess gEBV model performance. Utilizing a dataset from The Seeing Eye organization, which includes German Shepherds (n = 482), Golden Retrievers (n = 239), Labrador Retrievers (n = 1188), and Labrador and Golden Retriever crosses (n = 111), we assessed model performance within and across different breeds, trait heritability, case counts, and SNP marker densities. Our results indicate that no significant differences were found in model performance across varying heritabilities, case counts, or SNP densities, with all models performing similarly. Given its lack of need for parameter optimization, GBLUP was the most efficient model. Distichiasis showed the highest overall predictive performance, likely due to its higher heritability, while anodontia and distraction exhibited moderate accuracy, and oral papillomatosis had the lowest accuracy, correlating with its low heritability. These findings underscore that lower density SNP datasets can effectively construct gEBVs, suggesting that high-cost, high-density genotyping may not always be necessary. Additionally, the similar performance of all models indicates that simpler models like GBLUP, which requires less fine tuning, may be sufficient for genomic prediction in canine breeding programs. The research highlights the importance of standardized phenotypic assessments and carefully constructed reference populations to optimize the utility of genomic selection in canine breeding programs. Full article

Different types of feline papillomaviruses (PVs) are associated with a variety of skin lesions and neoplasia, such as papillomas and cell carcinomas, but the virus can also be found in healthy skin. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of veterinary experts on feline infectious diseases from 11 European Countries, discusses the current knowledge of feline PV infections. Cats most likely become infected through lesions or abrasions of the skin. Most PV infections remain asymptomatic. Besides cat-specific PVs, DNA sequences most closely related to human and bovine PVs have been detected in feline skin lesions. Diagnosis is supported by the histological detection of PV-induced cell changes and intralesional detection of viral antigen (immunostaining) or viral DNA (in situ hybridization). Immunostaining of p16CDKN2A protein (p16) can be performed as a proxy marker for PV-induced neoplasms. There is no specific treatment for PV-induced skin lesions. Spontaneous regression commonly occurs. In the case of invasive squamous cell carcinoma (ISCC), complete excision should be considered, if possible. Full article

The Buschke–Löwenstein tumor (BLT), also known as giant condyloma acuminatum, is a rare, exophytic tumor, arising from pre-existing warty lesions associated with human papillomavirus (HPV) infection, particularly strains 6 and 11, which are considered to have low oncogenic potential. BLT presents as a large, cauliflower-like growth typically affecting the penis, vulva, vagina, perineum, scrotum, anus, and perianal area. Despite being a benign lesion, BLT is locally aggressive with a high recurrence rate, and can potentially undergo malignant transformation into squamous cell carcinoma, contributing to an overall mortality rate of 20–30%. The primary treatment is complete surgical excision with wide margins, frequently requiring complex reconstructive techniques for defect coverage. We report on a 68-year-old patient, with multiple comorbidities, who presented with a two-year history of a large exophytic tumor in the genital region, affecting the penis, along with progressive erectile dysfunction and urinary problems. The tumor was surgically excised with oncological safety margins, and reconstruction was performed using advancement and rotation flaps from the scrotum and intact penile skin. Histopathological examination confirmed the diagnosis of Giant Condyloma (Buschke–Löwenstein tumor), showing acanthosis, papillomatosis, parakeratosis, and koilocytic cell collections, with positive immunohistochemical staining for p16, p63, and ki67. Postoperatively, the patient had a good clinical outcome and a complete surgical cure. This case highlights the critical need for timely intervention and comprehensive management strategies in treating giant condyloma, given its potential for local invasion and substantial impacts on patient quality of life. Early diagnosis and thorough surgical excision are crucial for effective management and to reduce the high recurrence, morbidity and malignant transformation risk associated with this condition. Full article

Juvenile- and adult-onset recurrent respiratory papillomatosis (JORRP and AORRP) are rare but serious conditions that are caused by oral human papillomavirus (HPV) infections. The proliferation of wart-like growths throughout the respiratory tract can result in medical problems, including death. The current treatment scheme is surgery, though prevention of HPV infection through vaccination is available. A previously developed model for JORRP and AORRP was adapted to the United States using data on disease burden and HPV infection. The model was validated against post-vaccination reductions in disease and used to forecast the future burden of JORRP and AORRP, estimating the impact that HPV vaccination will have on these diseases. Between 2007 (the beginning of HPV vaccination in the US) and 2021, this model estimates that approximately 1393 lives, 22,867 Quality-Adjusted-Life-Years, and over USD 672 million in treatment costs have been saved by HPV vaccination. There is also a substantial reduction in JORRP and AORRP burden, with a 95% reduction in incidence by 2040. Moreover, between 2040 and 2121, the model predicts 3–11 total cases of HPV6/11-related JORRP in the US, and 36–267 total cases of HPV6/11-related AORRP. HPV vaccination in the United States has driven, and will continue to drive, substantial reductions in the public health and economic burden of HPV6/11-related JORRP and AORRP. Full article

Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aerodigestive tract caused by human papillomavirus (HPV) types 6 and 11. The clinical course is unpredictable and some patients, especially younger children, experience a high rate of recurrence with a significant impact on their quality of life. The molecular mechanisms of HPV infection in keratinocytes have been extensively studied throughout the years, with particular regard to its role in causing malignant tumors, like cervical cancer and head and neck carcinomas. A minor but not negligible amount of the literature has investigated the molecular landscape of RRP patients, and some papers have studied the role of angiogenesis (the growth of blood vessels from pre-existing vasculature) in this disease. A central role in this process is played by vascular endothelial growth factor (VEGF), which activates different signaling cascades on multiple levels. The increased knowledge has led to the introduction of the VEGF inhibitor bevacizumab in recent years as an adjuvant treatment in some patients, with good results. This review summarizes the current evidence about the role of VEGF in the pathophysiology of RRP, the molecular pathways activated by binding with its receptors, and the current and future roles of anti-angiogenic treatment. Full article

Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient’s symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases. Full article