Search Results (279)

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

Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose vaccination schedule. The objective of this review is to critically examine the current HPV vaccination landscape in China, including vaccination policies, immunization schedules, supply–demand dynamics, and the feasibility of transitioning to a single-dose regimen. By synthesizing recent developments in HPV virology, epidemiology, vaccine types, and immunization strategies, we identify both opportunities and barriers unique to the Chinese context. Results indicate that China primarily adheres to a three-dose vaccination schedule, with an optional two-dose schedule for girls aged 9–14, leaving a notable gap compared to the most recent WHO recommendation. The high prevalence of HPV types 52 and 58 contributes to a distinct regional infection pattern, underscoring the specific need for nine-valent vaccines tailored to China’s epidemiological profile. Despite the growing demand, vaccine supply remains inadequate, with an estimated annual shortfall of more than 15 million doses. This issue is further complicated by strong public preference for the nine-valent vaccine and the relatively high cost of vaccination. Emerging evidence supports the comparable efficacy and durable protection of a single-dose schedule, which could substantially reduce financial and logistical burdens while expanding coverage. This review advocates for the adoption of a simplified single-dose regimen, supported by catch-up strategies for older cohorts and the integration of HPV vaccination into China’s National Immunization Program (NIP). Sustained investment in domestic vaccine development and centralized procurement of imported vaccines may also possibly alleviate supply shortage. These coordinated efforts are critical for strengthening HPV-related disease prevention and accelerating China’s progress toward the WHO’s cervical cancer elimination targets. 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

Cervical cancer (CC) is the gynecological cancer with the highest incidence and mortality worldwide. High-risk oncogenic human papillomaviruses (HPV) genotypes 16 and 18 are the primary risk factors for developing this female neoplasm, with them being the etiological agents of 70% of cervical cancers. Despite the availability of various prevention strategies, laboratory tests capable of detecting the disease in its previous and early stages, and multiple treatment schemes, CC incidence and mortality rates remain high, due in part to the population’s rejection or disinterest in the current type of sampling. An alternative that could encourage women to take better care of their gynecological health is the availability of tests that detect biomarkers in non-cervical samples with high sensitivity and specificity. The detection of biomarkers in non-cervical samples (blood, serum, plasma, urine, and vaginal fluids) may help reduce the discomfort associated with cervical sampling in patients, therefore promoting gynecological healthcare. This review discusses current diagnostic methods and recent advances in CC biomarkers detected in non-cervical samples, emphasizing their potential for diagnosis, prognosis, and patient monitoring. We further discuss the challenges and future perspectives of applying these biomarkers in clinical practice. The results of this review show that there is a considerable range of biomarkers proposed as alternative tools with high efficacy. Their identification in previous stages of the disease and routinely in non-cervical samples could help reduce the incidence and mortality rates of CC. Full article

Cervical cancer remains a global health burden, with persistent infection by high-risk human papillomaviruses (HR-HPVs) being the primary etiological factor. HR-HPVs target stem-like cells of the cervical epithelium to establish chronic infections. Upon infection of the cervical transformation zone (TZ)—a region adjacent to the squamocolumnar junction (SCJ)—these viruses drive neoplastic transformation, which is due in part to the unique cellular composition and hormonal responsiveness of the TZ. Reserve cells, which can accumulate at the cervical crypt entrances of the TZ, are thought to be highly susceptible to HR-HPV infection because of their location beneath a single layer of columnar cells. Infection of the stratified ectocervical epithelium, in contrast, requires a wound to allow basal cell infection, replication, and the expression of early genes to adjust epithelial homeostasis while facilitating immune evasion. Persistent infection by HR-HPV types, particularly HPV16 and HPV18, can result in the deregulated expression of viral genes E6 and E7, driving cell cycle disruption, genomic instability, and subsequent viral genome integration. Differences in the microenvironment and transcriptional environment of the ectocervix compared with the TZ could explain the frequent deregulation of E6 and E7 at the latter site, which can drive disease progression towards cancer. Full article

Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, generate a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the carcinogenesis of the female upper genital tract is neither clearly established not completely understood. Therefore, we performed a literature review, using the PubMed and SCOPUS electronic databases, of the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian, and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries on various continents. Overall, the prevalence of HPV was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0%, and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers, and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from tumors of the upper female reproductive tract, regardless of the tumor site, was HPV-16, followed by HPV-18. The HPV DNA identified was exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention of HPV-related carcinomas of the upper genital tract in women. Full article

Introduction: Anal squamous cell carcinoma (ASCC) is a rare but increasingly common gastrointestinal malignancy, mainly associated with oncogenic human papillomaviruses (HPVs). The role of non-coding RNAs (ncRNAs) in tumorigenesis is recognized, but the impact of viral ncRNAs on host gene expression remains unclear. Methods: We re-analyzed total RNA-Seq data from 70 anal biopsies: 31 low-grade squamous intraepithelial lesions (LGSIL), 16 high-grade SIL (HGSIL), and 23 ASCC cases. Microbial composition was assessed taxonomically. Novel viral miRNAs were predicted using vsRNAfinder and linked to host targets using TargetScan and expression correlation analyses. Results: Microbial profiling revealed significant differences in abundance, with Alphapapillomaviruses types 9, 10, and 14 enriched across lesion grades. We identified 90 novel viral miRNAs and 177 significant anti-correlated miRNA–mRNA interactions. Target genes were enriched in pathways related to cell cycle, epithelial–mesenchymal transition, lipid metabolism, immune modulation, and viral replication. Discussion: Our findings suggest that HPV-derived miRNAs, including those from low-risk types, may contribute to neoplastic transformation by modulating host regulatory networks. Conclusion: This study highlights viral miRNAs as potential drivers of HPV-related anal cancer and supports their utility as early biomarkers and therapeutic targets in ASCC. Full article

Human papillomaviruses (HPVs), like many other viruses, are able to integrate their genomes into the host cellular genome. This integration can activate viral oncogenes or alter the function of cellular oncogenes and tumor suppressor genes, thereby increasing the likelihood of HPV-associated tumor development. In particular, HPV types 16 and 18 are responsible for over 70% of all cervical, anal, and oropharyngeal cancers worldwide, with rising incidence. Even more, high-resolution mapping of preferred integration sites using LR-Seq technologies offers deep insights into the molecular mechanisms of HPV integration. LR-Seq enables the detection of complex integration patterns, where the viral genome can be replicated and amplified into virus–host concatemers, including events within large structural variations or highly repetitive genomic regions. Furthermore, aligning LR-Seq data to the latest T2T reference genome (hs1) is necessary to provide new information about viral integration in genomic regions that were previously inaccessible, such as centromeres and other structurally complex repeat-rich loci. In this review, we provide insights into HPV genomic integration revealed by LR-Seq technologies, with a particular focus on how the use of the complete T2T reference genome enhances the detection of integration events in previously uncharacterized, repeat-rich regions of the human genome. Full article

Papillomaviruses are small, circular DNA viruses that infect epithelial and mucosal cells, which have co-evolved with their hosts over time. While certain mammalian papillomaviruses—especially those linked to disease—are well studied, there is limited knowledge about papillomaviruses associated with avian species. In this study, we identified two avian papillomaviruses from eye/choana swabs of the sacred kingfisher (Todiramphus sanctus) and the little corella (Cacatua sanguinea), collected in Queensland, Australia. The genomes of these viruses, designated as todiramphus sanctus papillomavirus 1 (TsPV1) and cacatua sanguinea papillomavirus 1 (CsPV1), were found to be 7883 and 7825 base pairs in length, respectively. The TsPV1 and CsPV1 genomes exhibited the highest nucleotide sequence identity (>56%) with papillomavirus genomes previously sequenced from mallards or wild ducks in the United States, followed by those from black-legged kittiwakes and Atlantic puffins (>54%) in Newfoundland, Canada. Both TsPV1 and CsPV1 share approximately a 65% nucleotide sequence identity in the L1 gene with anas platyrhynchos papillomavirus 3 (AplaPV3), indicating that they represent novel avian papillomaviruses. Notably, the two genomes in this study were nearly identical (99.69%), and their L1 proteins shared 100% sequence identity. Phylogenetic analysis positioned TsPV1 and CsPV1 within a clade of avian papillomaviruses associated with closely related avian hosts, including the mallard, African grey parrot, common chaffinch, and Atlantic canary. These findings underscore the importance of further research on studying additional Australian bird species longitudinally, which will help to establish potential disease associations and ecological impacts of previously unrecognised and novel papillomaviruses in Australian wild birds. 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

Persistent high-risk human papillomaviruses (HR-HPVs) infection is the leading cause of cervical cancer. With over 200 circulating genotypes, HPV detection, management, and prevention remain challenging. In Benin, HPV prevalence and genotype distribution are largely unknown, and no national HPV vaccination program exists. This study investigates the prevalence, genotypic diversity, and risk factors of HIV–HPV co-infection among women in Cotonou, Benin. Cervical swabs were collected from 100 women living with HIV (WLWHIV) and 51 women without HIV (WWHIV) at two hospitals. DNA extraction and nested polymerase chain reaction (PCR) were used to detect HPV, followed by Sanger sequencing for genotyping. Chi-squared analysis was used to assess risk factors. HPV was detected in 85% (85/100) of WLWHIV and 60.8% (31/51) of WWHIV (p = 0.002), confirming HIV as an independent risk factor. Fifteen HR-HPV genotypes were identified, with HPV 45 most prevalent in WLWHIV and HPV 16 in WWHIV. Notably, HR-HPV 67, 70, and 82 were detected for the first time in Benin. Unmarried status and detectable HIV load were significant risk factors for co-infection. The high HPV prevalence, particularly among WLWHIV, underscores the urgent need for HPV surveillance and vaccination in Benin. Identifying novel HR-HPV genotypes highlights the necessity for ongoing monitoring and targeted prevention strategies. Full article

Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect epithelial cells and cause cervical, anogenital, and oropharyngeal cancers. HPV genome replication relies on the viral E1 and E2 proteins to initiate DNA replication. The first step is the assembly of the E1-E2 complex at the origin of replication. We have examined the role of full-length HPV E1 helicase and its interaction with E2 in pre-initiation complex formation. Electrophoretic mobility shift assays (EMSAs) with purified E1 and E2 proteins revealed that the HPV genome does not have a specific E1 binding site, or such a sequence is not required for pre-initiation complex formation. E1 alone did not show any binding to the origin DNA sequences, while E2 facilitated E1 recruitment to the origin, forming the E1-E2-DNA ternary complex. Formation of such a complex required at least two E2 binding sites. These findings led us to propose a novel mechanism in which E2 dimers serve as the primary recruiters of E1 to form the pre-initiation complex. This study provides new insights into the mechanistic role of E2 in the recruitment of E1 at the origin of HPV DNA replication, enhancing our understanding of HPV biology and potentially informing future therapeutic strategies. Full article

Epithelia contribute to the innate immune system through barrier formation and through signaling to immune cells. When the barrier is breached, epithelial cells undergo epithelial-to-mesenchymal transition (EMT) as part of the wound healing process. EMT is largely directed by signals from the stromal microenvironment, including transforming growth factor beta (TGFβ1), and antagonizes normal epithelial differentiation. How EMT and innate immunity may be connected molecularly has not been explored, although both processes are likely to occur simultaneously. Keratinocytes are the host cell type for human papillomaviruses (HPV), which can induce EMT in certain conditions but also depend on differentiation for their replication. We previously found that the innate immune factor interferon regulatory factor 3 (IRF3) inhibits epithelial differentiation and reduces the expression of HPV16 late genes. Here we report that IRF3 in the stroma compartment promotes an EMT-like pattern of gene expression in an HPV16-containing epithelium. The depletion of stromal IRF3 resulted in the downregulation of TGFβ1-related signaling in both the stroma and epithelium. IRF3 binds to the TGFB1 promoter in human foreskin fibroblasts and is necessary for TGFB1 mRNA production. Because an EMT-like state is unfavorable for differentiation-dependent HPV16, we observed that all EMT markers examined were reduced in the presence of episomal HPV16. Together, we show that stromal IRF3 can disrupt epithelial differentiation and act as an anti-HPV factor through the regulation of EMT, linking wound healing and immunity. Full article

The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing, with UV radiation being the main cause. Other risk factors are age, sex, skin type and immunosuppression. Human papillomaviruses (HPVs) are associated with benign and malignant skin tumours. In contrast to anogenital and oropharyngeal carcinomas, which are caused by alpha papillomaviruses, the HPV types associated with cSCC belong to the beta-HPV genus. These viruses infect the skin epithelium and are widespread in skin samples from healthy people. It is assumed that HPV amplifies the DNA damage caused by UV radiation and disrupts the repair mechanisms of the cells, without remaining permanently detectable in the tumour tissue, the so-called hit-and-run theory. The HPV status of tumours appears to have a positive influence on prognosis and response to therapy due to increased immune infiltration, in particular by tissue-resident memory T cells and activation of immune effector cells. This favours responses to immunotherapies such as PD-1/PD-L1 inhibitors, whereas immunosuppression may promote a pro-carcinogenic effect. In conclusion, the role of beta HPV in the development of cSCC appears to be closely associated with the immune status of the host. Depending on the immune status, beta HPV can play either a protective or a tumour-promoting role, and in view of the increasing incidence of skin cancer worldwide, enhancing the immune response against virus-infected keratinocytes, e.g., through HPV vaccination, could represent a promising approach for the prevention and therapy of squamous cell carcinomas. Full article

Papillomaviruses are double-stranded DNA viruses, and it is essential to clarify their genotypic distribution for their effective prevention and clinical management. In this study, we aimed to evaluate the prevalence of HPV genotypes in the normal oral mucosae of HIV-positive individuals. A systematic literature search was conducted across PubMed, Web of Science, Scopus, and Google Scholar to identify peer-reviewed studies published up to 13 February 2025. The inclusion criteria referred to original research studies reporting on the prevalence and genotype-specific distribution of HPV in the oral mucosae of HIV-positive individuals. Statistical analyses were conducted using the MedicReS E-PICOS AI smart biostatistics software (version 21.3, New York, NY, USA) and the MedCalc statistical software package (MedCalc Software Ltd., Ostend, Belgium). The pooled prevalence estimates were calculated using a random-effects meta-analysis model, and heterogeneity was quantified using the Cochrane Q and I² statistics. The presence of publication bias was assessed via the Begg and Mazumdar rank correlation test. High prevalence and heterogeneity of HPV-58 (6.23%), HPV-16 (4.326%), and HPV-66 (3.733%) were observed, indicating significant variability across populations and methodologies. This supports their association with HPV-related oropharyngeal malignancies and the need for the continuous surveillance of HIV-positive individuals. We also observed the elevated detection of LR-HPV genotypes, particularly HPV-13 (7.16%), HPV-5 (5.64%), and HPV-62 (4.24%). These findings indicate that there is substantial heterogeneity in the prevalence of both HR-HPV and LR-HPV genotypes among HIV-positive individuals, with certain genotypes exhibiting higher detection rates across studies, emphasizing the need for targeted surveillance and preventive strategies in this vulnerable population. The application of advanced data analysis methods is essential in enhancing HPV surveillance and implementing effective control measures in this vulnerable population. Full article