Search

Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV's 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development. [ABSTRACT FROM AUTHOR]

A six‐year‐old atopic boxer presented with pigmented viral plaques on the interdigital spaces and pinnae following treatment with potent topical glucocorticoids. The lesions regressed after treatment was discontinued, and recurred each time a topical glucocorticoid was resumed. A Chipapillomavirus was amplified from lesional tissue. [ABSTRACT FROM AUTHOR]

Over the last decades, the incidence of anal cancer has increased worldwide. The discovery of the HPV virus as its primary cause and the natural progression of the disease, involving precancerous lesions, have resulted in significant interest in screening for anal cancer. The use of cytology testing, high-risk HPV DNA research, high-resolution anoscopy, and their combination has been adopted with variable success in detecting anal HPV precancerous lesions. Various studies have been carried out to evaluate the sensitivity and specificity of these techniques in different populations. High-risk populations for developing anal cancer have been identified through study of incidence and prevalence. Therefore, different scientific societies and experts worldwide have provided different recommendations for screening, but a universal approach has not yet been established. The inhomogeneity of different risk groups, the variable accessibility to specifical techniques, and the lack of data regarding the cost–benefit ratio of screening are the main problems to address in order to define a consensus guideline acceptable worldwide. The purpose of this paper is to provide a comprehensive review of the literature on HPV precancerous lesions and its screening, particularly after the release of recent recommendations. [ABSTRACT FROM AUTHOR]

High-risk human papillomaviruses (HPVs) cause most cases of cervical cancer, a disease with an increasing impact worldwide. Recent studies have shown that the synthesis of viral oncoproteins is strongly subject to translational control. Thus, targeting the protein synthesis machinery might open novel avenues to develop innovative therapies aiming to improve patients' survival. [ABSTRACT FROM AUTHOR]

Background: Oral focal epithelial hyperplasia (FEH) is an uncommon infection affecting humans, chimpanzees, bonobos, and howler monkeys. This study describes 10 cases of free‐ranging brown howler monkeys (Alouatta guariba clamitans) diagnosed with FEH and Alouatta guariba Papillomavirus 1 (AgPV 1). Methods: We analyzed demographic characteristics, rescue conditions, clinical and pathological findings, and species‐specific behavior factors in these cases. The study assessed the frequency of occurrence and potential contributing factors of FEH and AgPV 1 infection. Results: The frequency of FEH was 8.13%. Most affected howlers were adult or geriatric males with comorbidities or stressful conditions. Clinical and pathological observations were consistent with AgPV 1 infection. Species‐specific behaviors and environmental stressors were identified as contributing factors. Conclusions: FEH associated with AgPV 1 affected mainly adult or geriatric males with ongoing comorbidities or stressful conditions. Further research is needed to understand these factors for effective management. [ABSTRACT FROM AUTHOR]

Background: In mid-2022 Australia's National Cervical Screening Program made self-collection of a vaginal sample an option for screening for young women or people with a cervix aged 25 to 29 years for the first time. This study explored what young women thought about, and wanted to know about, self-collection, and what their future screening preferences are. Methods: Young women (n = 21), aged 24–29 years, were recruited through social media. Semi-structured interviews explored screening history, screening preferences and thoughts about self-collection. Data were analysed using an a priori coding framework informed by the Theoretical Framework of Acceptability. Results: Young women valued the addition of self-collection to the national cervical screening program, believing it to be less invasive and more convenient. However, they also valued the choice to opt for a clinician-collected specimen if preferred. Conclusions: Self-collection is a valuable addition to the National Cervical Screening Program. This study suggests that continued efforts are needed to raise awareness of its availability, and improve understanding about its accuracy, the ease of collection, that you still need to engage with a primary healthcare service to access it and that you can still opt for a clinician-collected test. Now available for the first time to young women and people with a cervix (aged 25–29 years), self-collection cervical screening is a safe, accurate and easy method to complete regular cervical screening without the use of a speculum. However, the best ways to communicate and promote self-collection to this age group has not been researched. This is important, because self-collection creates a positive screening experience, and will encourage young people to continue screening throughout their life, ultimately preventing cervical cancer. [ABSTRACT FROM AUTHOR]

The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non‐HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)‐HPV and low risk (LR)‐HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR‐HPV 16, reinforcing the urge for a greater vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants. Objectives: The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study. Methods: Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques. Results: In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique. Conclusions: Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology. [ABSTRACT FROM AUTHOR]

Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous β-genus human papillomaviruses (β-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease: EVER1, EVER2, or CIB1. EVER1 and EVER2 are also known as TMC6 and TMC8, respectively. Little is known about the biochemical activities of EVER gene products or their roles in facilitating EV in conjunction with β-HPV infection. To investigate the potential effect of EVER genes on papillomavirus infection, we pursued in vivo infection studies by infecting Ever2-null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with β-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and Ever2-null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between Ever2-null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in Ever2-null mice compared with wild-type mice. These studies demonstrate that Ever2-null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with β-HPVs. IMPORTANCE Humans with homozygous mutations in the EVER2 gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent β-genus human papillomavirus (β-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous Ever2-null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected Ever2-null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these Ever2-null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in Ever2-null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and β-HPVs and/or between mouse and human EVER2. [ABSTRACT FROM AUTHOR]

DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals, and, therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double-stranded DNA viruses that may establish lifelong latency and can produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA, and these ancient viral genomes showed divergence consistent with the age of these samples (≈50,000 years) and viral evolutionary rates (10−5 to 10−8 substitutions/site/year). Analysis of random effects showed that the Neanderthal mapping to genomes of extant persistent viruses is above what is expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment. [ABSTRACT FROM AUTHOR]

Liver transplant recipients have an increased risk of anal squamous cell carcinoma. High-risk patient groups have been identified, especially women who have received liver transplant for more than 10 years. New screening guidelines were published in January 2024. The aim is to screen high-grade dysplastic lesions, whose treatment has been shown to reduce the occurrence of squamous cell carcinoma. A HPV16 test is suggested, followed by clinical examination and anal cytology. If cytological lesions are found, high-resolution anoscopy should be performed. Liver transplant and colo-proctology teams need to organize systematic screening. [ABSTRACT FROM AUTHOR]

A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high‐risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real‐time sequencing (SMRT) and evaluated its performance against MY09‐11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09‐11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR‐HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR‐HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype. [ABSTRACT FROM AUTHOR]

Objective: Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. Methods: Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. Results: Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. Conclusion: Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. Level of Evidence: NA Laryngoscope, 134:2322–2330, 2024 [ABSTRACT FROM AUTHOR]

Domestic dogs are currently recognized as being infected by 25 different canine papillomavirus (CPV) types classified into three genera. A short sequence from a novel CPV type was amplified, along with CPV1, from a papilloma (wart) from the mouth of a dog. The entire 7499 bp genome was amplified, and CPV26 contained putative coding regions that were predicted to produce four early proteins and two late ones. The ORF L1 showed less than 62% similarity for all previously sequenced CPV types but over 69% similarity to multiple Omegapapillomavirus types from a variety of Caniform species including the giant panda, Weddel seal, and polar bear. Phylogenetic analysis confirmed CPV26 clusters within the Omegapapillomavirus genus. Specific primers were used to investigate the presence of CPV26 DNA within a series of 37 canine proliferative lesions. CPV26 DNA was amplified from one lesion, a cutaneous papilloma that also contained CPV6. This is the first time a PV type within the Omegapapillomavirus genus has been detected in a non-domestic species and this provides evidence that the omegapapillomaviruses infected a common ancestor of, and then co-evolved with, the Caniform species. Whether CPV26 causes disease is uncertain, but the absence of an E7 protein may suggest low pathogenicity. [ABSTRACT FROM AUTHOR]

Simple Summary: The human papillomavirus (HPV), a major carcinogenic pathogen, can cause cervical cancer through persistent infection. The immune system typically fights off the virus, albeit long-term activation may promote carcinogenesis. The micro-immunotherapy medicine 2LPAPI® holds promise for aiding viral clearance and mitigating cervical cancer risk, and our research aimed to examine the effects of this medicine in vitro. We focused our investigations on the two most prevalent genotypes of HPV causing persistent infection, HPV-16 and HPV-18. We found that 2LPAPI® boosted the secretion of IL-6, IFN-γ, and IP-10 in human immune cells when exposed to HPV-16 proteins, suggesting enhanced defensive responses to HPV-16. Some of the active substances curtailed T-cell proliferation and activity and displayed antiproliferative properties on HPV-18 positive cervical cancer-derived HeLa cells in nutrient-restricted conditions. These results unveil 2LPAPI®'s potential dual role: immunomodulation for HPV-16-affected immune cells and antiproliferative activity against a model of HPV-18-positive-cervical cancer cells. Human papillomavirus (HPV) is the second most common infectious agent causing cancer. Persistent infection with high-risk (HR)-HPV can lead to cervical intra-epithelial neoplasia and cervical carcinomas (CC). While host immune response is necessary for viral clearance, chronic immune activation contributes to a low-grade inflammation that can ultimately lead to carcinogenesis. The micro-immunotherapy medicine (MIM) 2LPAPI® could be a valuable tool to manage the clearance of the virus and reduce the risk of developing CC. In this in vitro study, we aimed to investigate its mode of action. We showed that actives from the MIM increased the IL-6, IFN-γ, and IP-10 secretion in human peripheral blood mononuclear cells (PBMCs) exposed to peptides derived from the HPV-16 capsid (HPV16(L1)). This could reflect an increase in the immune activity toward HPV-16. At the same time, some active substances reduced the lympho-proliferation and the expression of T-cell activation markers. Finally, some of the MIM actives displayed antiproliferative effects in CC-derived HeLa cells under serum-starvation conditions. Altogether, this body of data highlighted for the first time the dual effect of MIM in the framework of HR-HPV infections as a potential (i) immune modulator of HPV16(L1)-treated PBMCs and (ii) antiproliferative agent of HPV-positive CC cells. [ABSTRACT FROM AUTHOR]

Abstract Background Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants. Objectives The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study. Methods Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques. Results In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique. Conclusions Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology.

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 102 to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses. HIGHLIGHTS This study aimed to investigate the occurrence and seasonality variation of HAdV, HPyV, and HPV in raw sewage collected regularly over 12 months from sewage pump stations.; This study represents the first data about the occurrence of HAdV, HPyV, and HPV in Zagazig city, Al Sharqia Governorate, Egypt.; This study supports using both HAdV and HPyV as indicators than either of them as a single fecal indicator.;

ABSTRACTTo summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Introduction: Human Papillomavirus (HPV) with small size and double-stranded DNA is the most important cause of sexually transmitted infections and cervical carcinoma. Controlling the spread of papillomavirus infection and protecting people against the pathogenicity of this virus are key steps in reducing the number of cervical cancer patients. One of the effective ways to achieve this goal is to design a suitable vaccine. In the present study, computer-aided methods were used to suggest a potential vaccine candidate against HPV. Methods: Oncoproteins L1 and E5 of the high-risk strain HPV 16 were utilized to predict the linear B-cell epitopes, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) epitopes. From the obtained epitopes, non-allergenic and non-toxic peptides with acceptable antigenicity were selected and subsequently converted into 3D structures. The epitopes were subjected to molecular docking using the PDB format. In the next step, short amino acid sequences as spacers were used to join peptides together. Finally, computational analysis including allergenicity and antigenicity studies, physicochemical properties, secondary and tertiary structure prediction, molecular interaction pattern, and cloning analyses were conducted for the vaccine construct. Results: Our findings revealed that the designed vaccine with suitable antigenicity and physicochemical properties, shows proper interaction with four types of Toll-like receptors (TLR3, TLR4, TLR5, and TLR8), and Escherichia coli (strain K12) is the suitable host for it. Conclusion: Overall, the vaccine designed in the present study showed a promising immune response. However, further validation through laboratory investigations is required. [ABSTRACT FROM AUTHOR]

Nanotechnology products such as titanium dioxide nanoparticles (TiO2-NPs) can be used for viral infections because of their unique characteristics. The current study aimed to determine the impact of TiO2-NPs on HPV type 1 and 2 infections. The characterization of these NPs was performed using dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). The MTT assay was used to determine the toxic impacts of TiO2-NPs on BHK-21 cells. The efficiency of TiO2-NPs was performed using several parameters, including TCID50 and RT-PCR assays. An indirect immunofluorescence assay (IFA) was performed to estimate the inhibitory impact of TiO2-NPs on viral antigen expression, and Acyclovir was used as a reference medicine. When the human papilloma type 1 and 2 viruses exposed to TiO2-NPs at high doses (100 μg/mL) produced 0.3, 1.1, 2.3, and 3.3 log10 TCID50 decreases in infective virus load when compared with control viruses (P<0.0001), these TiO2-NPs doses were related to 24.9%, 35.1%, 47.2%, 59.5%, and 66.6% inhibition percentages that were determined depending on the viral titer as compared to virus control. It is concluded that TiO2-NPs have strong potential for the treatment of face and labial lesions caused by papillomaviruses 1 and 2 and could be used in topical formulations. [ABSTRACT FROM AUTHOR]

An approximately 10-year-old, castrated male domestic short-haired cat developed swelling and ulceration of the second digit of the right front paw. Radiographs revealed a spherical soft tissue swelling with irregular distal margins that contained multiple lacy mineral opacities. The digit was amputated and submitted for histology. No recurrence has been observed 7 months after amputation. Histology revealed a moderately well-circumscribed proliferation of well-differentiated squamous cells arranged in trabeculae and nests. Numerous thin spicules of osseous metaplasia were visible throughout the neoplasm. Around 70% of the neoplastic cells contained papillomavirus-induced cell changes including large amphophilic cytoplasmic bodies and cells with shrunken nuclei surrounded by a clear halo. Intense p16CDKN2A protein immunostaining was visible within the neoplastic cells, suggesting papillomavirus-induced changes in cell regulation. A DNA sequence from a putative novel Taupapillomavirus type was amplified from the neoplasm. Osteoinductive squamous cell carcinoma associated with a putative novel papillomavirus type. The findings in this case increase the number of papillomavirus types known to infect cats, and the squamous cell carcinoma had histological features that have not been previously reported. The neoplasm was not as invasive as is typical for a squamous cell carcinoma and excision appeared curative. This is the first report of an osteoinductive squamous cell carcinoma of the skin of cats and the neoplasm had a unique radiographic appearance. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56× 10² to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. E7 is degraded through ubiquitination mediated by cullin 1 (CUL1) and the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, E7 proteins are maintained at high levels in most HPV-positive cancer cells. A previous proteomics study has shown that UBE2L3 and CUL1 protein levels are increased by the knockdown of the E3 ubiquitin ligase membraneassociated ring-CH-type finger 8 (MARCHF8). We have recently demonstrated that HPV16 upregulates MARCHF8 expression in HPV-positive keratinocytes and head and neck cancer (HPV+ HNC) cells. Here, we report that MARCHF8 stabilizes the HPV16 E7 protein by degrading the components of the S-phase kinase-associated protein 1-CUL1-F-box ubiquitin ligase complex in HPV+ HNC cells. We found that MARCHF8 knockdown in HPV+ HNC cells drastically decreases the HPV16 E7 protein level while increasing the CUL1 and UBE2L3 protein levels. We further revealed that the MARCHF8 protein binds to and ubiquitinates CUL1 and UBE2L3 proteins and that MARCHF8 knockdown enhances the ubiquitination of the HPV16 E7 protein. Conversely, the overexpression of CUL1 and UBE2L3 in HPV+ HNC cells decreases HPV16 E7 protein levels and suppresses tumor growth in vivo. Our findings suggest that HPV-induced MARCHF8 prevents the degradation of the HPV16 E7 protein in HPV+ HNC cells by ubiquitinating and degrading CUL1 and UBE2L3 proteins. IMPORTANCE Since human papillomavirus (HPV) oncoprotein E7 is essential for virus replication; HPV has to maintain high levels of E7 expression in HPV-infected cells. However, HPV E7 can be efficiently ubiquitinated by a ubiquitin ligase and degraded by proteasomes in the host cell. Mechanistically, the E3 ubiquitin ligase complex cullin 1 (CUL1) and ubiquitin-conjugating enzyme E2 L3 (UBE2L3) components play an essential role in E7 ubiquitination and degradation. Here, we show that the membrane ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8) induced by HPV16 E6 stabilizes the E7 protein by degrading CUL1 and UBE2L3 and blocking E7 degradation through proteasomes. MARCHF8 knockout restores CUL1 and UBE2L3 expression, decreasing E7 protein levels and inhibiting the proliferation of HPV-positive cancer cells. Additionally, overexpression of CUL1 or UBE2L3 decreases E7 protein levels and suppresses in vivo tumor growth. Our results suggest that HPV16 maintains high E7 protein levels in the host cell by inducing MARCHF8, which may be critical for cell proliferation and tumorigenesis. [ABSTRACT FROM AUTHOR]

Adolescents are the primary cohort for routine human papillomavirus (HPV) vaccination, but unvaccinated adults may also benefit. A lack of consensus on which adults to target and the presence of reimbursement barriers likely contribute to the lag in adult vaccinations, highlighting missed prevention opportunities. Understanding factors contributing to risk of HPV infection and disease could help in decision making on vaccination. This review summarizes existing literature on risk factors for HPV infection and disease and includes 153 studies reporting relative risks or odds ratios for factors associated with HPV infection or disease in adults, published between 2009 and 2020. Despite inconsistent design and reporting of risk factors across studies, this review confirmed several risk factors associated with adult infection, including human immunodeficiency virus positivity, number of sex partners, and smoking. These findings can support policymaking, guideline development, and clinical decision making for HPV vaccination and screening of high‐risk adult groups. [ABSTRACT FROM AUTHOR]

Polyomaviruses are widely distributed viruses of birds that may induce developmental deformities and internal organ disorders primarily in nestlings. In this study, polyomavirus sequence was detected in kidney and liver samples of a common kestrel (Falco tinnunculus) that succumbed at a rescue station in Hungary. The amplified 5025 nucleotide (nt) long genome contained the early (large and small T antigen, LTA and STA) and late (viral proteins, VP1, VP2, VP3) open reading frames (ORFs) typical for polyomaviruses. One of the additional putative ORFs (named VP4) showed identical localization with the VP4 and ORF-X of gammapolyomaviruses, but putative splicing sites could not be found in its sequence. Interestingly, the predicted 123 amino acid (aa) long protein sequence showed the highest similarity with human papillomavirus E4 early proteins in respect of the aa distribution and motif arrangement implying similar functions. The LTA of the kestrel polyomavirus shared <59.2% nt and aa pairwise identity with the LTA sequence of other polyomaviruses and formed a separated branch in the phylogenetic tree among gammapolyomaviruses. Accordingly, the kestrel polyomavirus may be the first member of a novel species within the Gammapolyomavirus genus, tentatively named Gammapolyomavirus faltin. [ABSTRACT FROM AUTHOR]

Background: The skin and its appendages are among the main organs susceptible to neoplasms in cats. Squamous cell carcinoma (SCC) is a malignant neoplasm that affects the epidermis, is locally invasive, and presents with low metastases; however, when it occurs, it spreads to the regional lymph nodes, lungs, and bone tissue. It can present in both proliferative and ulcerative forms. Its etiopathogenesis has not been fully established; however, it is associated with chronic sun exposure, papillomavirus infection, immunosuppression, and chronic skin diseases. This tumor mainly affects white-coated cats but also dark cats with hypopigmented areas, which are uncommon in dark animals and in those with good coat coverage. The objective of this study was to report a case of cutaneous SCC in a cat with black fur. Case: A 14-year-old, 4.5-kg, mixed-breed cat with black fur and a history of an ulcerated wound in the periocular region that did not heal even after previous treatment was treated with 30 mg/kg cephalexin twice a day for 15 days, 1 mg/kg prednisolone once a day for 5 days, and daily cleaning of the wound with 1% chlorhexidine twice a day for 15 days. In order to obtain a definitive diagnosis, cytological and histopathological examinations were performed. First, fine needle aspiration, an imprint, and a swab of the periocular lesion were taken. Immature or dysplastic squamous epithelium cells were observed, with keratinized polygonal angular cytoplasm, oval nuclei and coarse chromatin, a high nucleus:cytoplasm ratio, a large amount of red blood cells, and a moderate amount of segmented neutrophils, macrophages, and cocci-shaped bacteria. Fragments of malignant neoplasms invading the muscle tissue were also observed, characterized by "islands" of epithelial cells with large pleomorphic nuclei, multiple nucleoli, numerous mitotic figures, and formation of corneal pearls, leading to a diagnosis of SCC. Importantly, the animal's blood count remained unchanged. Treatment was established with the use of gabapentin [10 mg/kg - twice daily for 10 days], clindamycin [25 mg/kg - twice daily for 14 days], and piroxicam [0.3 mg/kg - every other day for 20 days]. For topical use, a cream was prepared with 5% papain, 4% hydroviton, and sunscreen (SPF 50) for use twice a day, as well as ointment based on gentamicin sulfate, sulfanilamide, sulfadiazine, urea, vitamin A palmitate, 2-3 times a day for 15 days. However, the neoplasm was already invasive, and the animal died before the treatment was completed. Discussion: Although the etiopathogenesis is not well understood, it is known that the occurrence of SCC in animals with dark fur and good coat coverage is slightly associated with chronic exposure to sunlight, which mostly affects cats with light fur or those with hypopigmented areas, as well as hair scarcity. However, in addition to ultraviolet radiation, papillomaviruses and other factors can cause SCC. The best form of diagnosis for this pathology is cytopathological examination, and if this is inconclusive, it is followed by confirmation with histopathological examination. There are several ways to treat this neoplasm, among them are surgical removals, chemotherapies, radiotherapies, photodynamic therapies, cryosurgeries, cyclooxygenase-2 and tyrosine kinase receptor inhibitors, electrochemotherapy and the use of antineoplastic agents therefore, it is important to individualize treatment according to the case and the financial status of the owner. The importance of early diagnosis is emphasized so that the tumor does not become invasive and metastasize over time, thus increasing the chances of a cure. [ABSTRACT FROM AUTHOR]

Les papillomavirus humains à haut risque oncogène (HPV-HR) sont des virus à tropisme muqueux dont la persistance est responsable du développement de cancers. Un HPV-HR est retrouvé dans près de 100 % des cas de cancer du col, 90 % des cancers anaux, 50 % des cancers génitaux et 30 % des cancers ORL. Les oncoprotéines E6 et E7 des HPV-HR, l'intégration du génome viral et des mécanisme épigénétiques participent à la mise en place du processus carcinogène. Parmi les marqueurs biologiques associés à la présence de lésions précancéreuses ou cancéreuses, on retrouve la détection et le typage des HPV-HR, le double immunomarquage pl6/Ki67, l'analyse de méthylation des gènes viraux ou cellulaires, l'intégration du génome viral ou encore la sérologie dirigée contre les oncoprotéines virales. Néanmoins, tous ces marqueurs n'ont pas la même performance et celle-ci varie en fonction du type de cancer. Pour celui du col, la détection des HPV-HR a un rôle central dans le dépistage et les autres biomarqueurs, notamment de méthylation, doivent encore être évalués et bénéficier de processus d'automatisation avant de trouver leur place dans l'algorithme de dépistage. Pour le cancer de l'anus, le typage de l'HPV16 a récemment intégré l'algorithme de dépistage tandis que la méthylation et la sérologie doivent encore bénéficier de validations cliniques pour confirmer leur intérêt. Les cancers ORL liés aux HPV ne bénéficient pas, à ce jour, de biomarqueurs pertinents de dépistage. Les nouveaux développés présentent souvent une très bonne sensibilité, mais une spécificité insuffisante pour envisager leur utilisation dans le cadre d'une stratégie de dépistage. High-risk human papillomaviruses (HPV-HR) are viruses with a mucosal tropism whose persistence is responsible for the development of cancers. HPV-HR is found in almost 100 % of cervical cancers, 80 % of anal cancers, 50 % of genital cancers and 30 % of ENT cancers. HPV-HR oncoproteins E6 and E7, viral genome integration and epigenetic mechanisms all play a part in setting up the carcinogenic process. Biological markers associated with the presence of pre-cancerous or cancerous lesions include HPV-HR typing, pl6/Ki67 double immunostaining, viral or cellular gene methylation analysis, viral genome integration and serology directed against viral oncoproteins. However, not all these markers have the same performance, and this varies according to the type of cancer. For cervical cancer, HPV-HR typing plays a central role in screening, while other biomarkers, notably methylation, still need to be evaluated and automated before they can find their place in the screening algorithm. In the case of anal cancer, HPV16 typing has recently been incorporated into the screening algorithm, while methylation and serology have yet to benefit from clinical validation to confirm their value. HPV-related ENT cancers do not currently benefit from relevant screening biomarkers. The new biomarkers that have been developed often have very good sensitivity, but insufficient specificity to be used as part of a screening strategy. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor, and more than 90% of feline MCC cases test positive for Felis catus papillomavirus type 2 (FcaPV2). In the present study, basal cell markers p40, p63, and p73 and the stem cell marker SOX2 and cytokeratin 14 (CK14) were immunohistochemically examined in normal fetal, infant, and adult feline skin tissues. The expression of these proteins was examined in tumors positive for FcaPV2, including MCC, basal cell carcinoma (BCC), Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Infant and adult feline skin tissues had mature Merkel cells, which were CK14-, CK18+, CK20+, SOX2+, synaptophysin+ and CD56+, while fetal skin tissue had no mature Merkel cells. MCC was immunopositive for p73, CK18, and SOX2 in 32/32 cases, and immunonegative for CK14 in 31/32 cases and for p40 and p63 in 32/32 cases. These results indicate that MCC exhibits different immunophenotypes from Merkel cells (p73-) and basal cells (p40+, p63+, and SOX2-). In contrast, all 3 BCCs, 1 BISC, and 2 SCCs were immunopositive for the basal cell markers p40, p63, and p73. The life cycle of papillomavirus is closely associated with the differentiation of infected basal cells, which requires the transcription factor p63. Changes in p63 expression in FcaPV2-positive MCC may be associated with unique cytokeratin expression patterns (CK14-, CK18+, and CK20+). Furthermore, SOX2 appears to be involved in Merkel cell differentiation in cats, similar to humans and mice. [ABSTRACT FROM AUTHOR]

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Juvenile onset recurrent respiratory papillomatosis is a lifelong benign squamous lesion associated with HPV infection, particularly HPV6 and HPV11 genotypes. These lesions are rare, but can lead to laryngeal obturations, which can cause disabling dyspnea, or transform into squamous cell carcinoma. The aim here is to provide an epidemiological, biological and clinical overview of this pathology, particularly in children, in order to understand the issues at stake in terms of research and the development of medical and therapeutic management tools.

ABSTRACT Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.

ABSTRACT An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 and BRD4 is required for E2 plasmid segregation function. The E2-TopBP1 interaction promotes increased mitotic E2 protein levels in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes immortalized by HPV16 (HFK + HPV16). SIRT1 deacetylation reduces E2 protein stability and here we demonstrate that increased E2 acetylation occurs during mitosis in a TopBP1 interacting-dependent manner, promoting E2 mitotic stabilization. p300 mediates E2 acetylation and acetylation is increased due to E2 switching off SIRT1 function during mitosis in a TopBP1 interacting-dependent manner, confirmed by increased p53 stability and acetylation on lysine 382, a known target for SIRT1 deacetylation. SIRT1 can complex with E2 in growing cells but is unable to do so during mitosis due to the E2-TopBP1 interaction; SIRT1 is also unable to complex with p53 in mitotic E2 wild-type cells but can complex with p53 outside of mitosis. E2 lysines 111 and 112 are highly conserved residues across all E2 proteins and we demonstrate that K111 hyper-acetylation occurs during mitosis, promoting E2 interaction with Topoisomerase 1 (Top1). We demonstrate that K112 ubiquitination promotes E2 proteasomal degradation during mitosis. E2-TopBP1 interaction promotes mitotic acetylation of CHK2, promoting phosphorylation and activation of the DNA damage response (DDR). The results present a new model in which the E2-TopBP1 complex inactivates SIRT1 during mitosis, and activates the DDR. This is a novel mechanism of HPV16 activation of the DDR, a requirement for the viral life cycle.IMPORTANCEHuman papillomaviruses (HPVs) are causative agents in around 5% of all human cancers. While there are prophylactic vaccines that will significantly alleviate HPV disease burden on future generations, there are currently no anti-viral strategies available for the treatment of HPV cancers. To generate such reagents, we must understand more about the HPV life cycle, and in particular about viral-host interactions. Here, we describe a novel mitotic complex generated by the HPV16 E2 protein interacting with the host protein TopBP1 that controls the function of the deacetylase SIRT1. The E2-TopBP1 interaction disrupts SIRT1 function during mitosis in order to enhance acetylation and stability of viral and host proteins. We also demonstrate that the E2-TopBP1 interaction activates the DDR. This novel complex is essential for the HPV16 life cycle and represents a novel anti-viral therapeutic target.

Background: Vaccination against Human papillomavirus (HPV) is recommended to avoid HPV infections and its associated diseases, including cervical cancer. However, there is no awareness study among Bangladeshi population. Hence, this nationwide study was conducted to explore HPV vaccine awareness and its determinants among parents of eligible adolescent girls. Methods: This study was conducted among the parents of daughters aged 9–15 years from 42 out of 64 randomly selected districts of Bangladesh between June 28 to August 2, 2023. A multistage sampling method was used to enroll 2151 study participants from all eight divisions of Bangladesh. A semi-structured questionnaire was used for face-to-face interviews in this study. The statistical software Stata (Version 17) was used for statistical analyses. Results: The average age of the participants was 38.18 (±5.86) years. Only 22.32 % of the participants were aware of the HPV vaccine. Every additional year of age increased the likelihood of being aware of the HPV vaccine by 3 % (AOR: 1.03; 95%CI: 1.00–1.06). Participants residing in the urban area had 3.56 times higher odds of awareness than rural and semi-urban people. Businessmen and housewives had 60 % (AOR: 0.40; 95 % CI: 0.22–0.69) and 77 % (AOR: 0.23; 95 % CI: 0.16–0.33) lower odds in comparison to job holders. The lower-income group exhibited significantly higher odds of awareness (AOR: 0.25, 95%CI: 0.16–0.39) compared to the middle and the higher-income group. Participants who never went through routine health check-ups had 77 % lower odds of being aware than those who availed of regular routine check-ups (AOR: 0.23; 95%CI: 0.16–0.34). Conclusion: Awareness of the HPV vaccine among the general population of Bangladesh is very low. Age, residence, occupation, monthly income, and routine medical check-ups were associated with HPV vaccine awareness. A nationwide awareness campaign would increase this awareness level among the Bangladeshi population, especially among the parents of daughters.

Abstract Background Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy. Methods We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis. Results Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes. Conclusions Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity.

Background: Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy. Methods: We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis. Results: Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes. Conclusions: Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity. [ABSTRACT FROM AUTHOR]

Objective: Laryngeal human papillomavirus (HPV) infection causes recurrent respiratory papillomatosis (RRP) and accounts for up to 25% of laryngeal cancers. Lack of satisfactory preclinical models is one reason that treatments for these diseases are limited. We sought to assess the literature describing preclinical models of laryngeal papillomavirus infection. Data Sources: PubMed, Web of Science, and Scopus were searched from the inception of database through October 2022. Review Methods: Studies searched were screened by two investigators. Eligible studies were peer‐reviewed, published in English, presented original data, and described attempted models of laryngeal papillomavirus infection. Data examined included type of papillomavirus, infection model, and results including success rate, disease phenotype, and viral retention. Results: After screening 440 citations and 138 full‐text studies, 77 studies published between 1923 and 2022 were included. Models used low‐risk HPV or RRP (n = 51 studies), high‐risk HPV or laryngeal cancer (n = 16), both low‐ and high‐risk HPV (n = 1), and animal papillomaviruses (n = 9). For RRP, 2D and 3D cell culture models and xenografts retained disease phenotypes and HPV DNA in the short term. Two laryngeal cancer cell lines were consistently HPV‐positive in multiple studies. Animal laryngeal infections with animal papillomaviruses resulted in disease and long‐term retention of viral DNA. Conclusions: Laryngeal papillomavirus infection models have been researched for 100 years and primarily involve low‐risk HPV. Most models lose viral DNA after a short duration. Future work is needed to model persistent and recurrent diseases, consistent with RRP and HPV‐positive laryngeal cancer. Level of Evidence: NA Laryngoscope, 133:3256–3268, 2023 [ABSTRACT FROM AUTHOR]

The virome of the skin, defined as all viruses detected in the skin, represents a significant part of the microbiota. A much more recent discovery than the bacterial flora, the existence of the cutaneous virome has been revealed by recent metagenomic studies. The normal human skin virome is dominated by bacteriophages, Papillomaviridae , whose genomic diversity has proved extraordinary, and Polyomaviridae. Many yet unknown viral genomes within this virome await identification. The composition of the virome of the skin has been shown to be strictly individual and relatively stable over time, resulting from adaptation to everyone's genetics, lifestyle and mechanisms of immunological tolerance finely selected over the course of evolution. Yet little studied, the virome of the skin and all its interactions with other microbiota and the host are attracting growing interest. Indeed, constitutional or acquired alterations in the homeostasis between the commensal virome and the skin, ranging from sub-clinical viral dysbiosis to severe transformation of keratinocytes or adnexal cells, have been observed. These recent observations are stimulating the search for innovative solutions aimed at measuring or even modulating its pathological expression, with a view to personalized medicine. [ABSTRACT FROM AUTHOR]

Copyright of Cirugía y Cirujanos is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Canine pigmented viral plaques (PVPs) are proliferative epidermal lesions caused by canine papillomaviruses (CPVs). Although the lesions are benign, neoplastic transformation has been reported. Cases reported in the literature are few and mainly focused on genome sequencing. The aim of this study was to collect data on the epidemiology, clinicopathological features, and genotyping of PVPs. Fifty-five canine PVPs were retrospectively retrieved and histologically evaluated. Follow-up was available for 33 cases. The median age was 6.5 years and pugs were the most represented breed (25%). There were 4 clinical presentations: a single lesion (24%), multiple lesions (75%) in one (41%) or different sites (34%), and generalized lesions all over the body (24%). The abdomen and axillae were the most common sites. In single lesions, no recurrence was observed after conventional surgery, whereas different medical treatments reported for multiple lesions were not successful. Spontaneous regression was reported in 3 cases. Neoplasia in contiguity with PVPs was seen in 5 of 55 lesions (9%), and 1 dog was euthanized due to invasive squamous cell carcinoma (SCC). The most useful histopathological features for diagnosis were scalloped profile, epidermal spikes, hypergranulosis, and hyperpigmentation. L1 immunolabeling was present in 14 of 16 cases (87%). Sequencing revealed that 10 of 16 cases were associated with CPV-9 (71%), 2 cases were associated with CPV-4 (14%), and 2 cases were associated with CPV-8 (14%). In conclusion, this represents a large cohort study on canine PVPs reporting data on clinicopathological features, therapy, outcome, and the type of CPV involved for the first time in Italy. [ABSTRACT FROM AUTHOR]

Erethizon dorsatum papillomavirus 1 (EdPV1) and Erethizon dorsatum papillomavirus 2 (EdPV2) are associated with cutaneous papillomas in North American porcupines (Erethizon dorsatum). This study defined gross, histopathologic, and molecular characteristics of viral papillomas in 10 North American porcupines submitted to the New York State Animal Health Diagnostic Center. Investigation for the presence of EdPV1 and EdPV2 DNA via polymerase chain reaction (PCR) was performed in 9 of the 10 (90.0%) porcupines, and all porcupines were investigated for the detection and localization of EdPV1 and EdPV2 E6 and E7 nucleic acid via chromogenic in situ hybridization (CISH). Next-generation sequencing (NGS) was performed in 2 porcupines. Papillomas were diagnosed on the muzzle (n = 4), caudal dorsum (n = 1), upper lip (n = 1), chin (n = 1), gingiva (n = 2), and nasal planum (n = 1). Histologically, the lesions consisted of hyperplastic epidermis or epithelium with orthokeratotic keratin, prominent keratohyalin granules, and intranuclear inclusion bodies. PCR identified EdPV1 in 6 of 9 samples and EdPV2 in the remaining 3 samples. NGS resulted in 100% genome coverage of EdPV1 and 76.20% genome coverage of EdPV2 compared with GenBank reference sequences, with 99.8% sequence identity to the complete EdPV2 L1 gene of a novel subtype recently identified in France. Hybridization patterns in 9 of the 10 (90.0%) porcupines were characterized by strong nuclear signals in the superficial epidermis, with strong nuclear and punctate cytoplasmic signals in the stratum spinosum and basale. In one animal, CISH suggested dual EdPV1 and EdPV2 infection. [ABSTRACT FROM AUTHOR]

The activity of proteins is thought to be invariably determined by their amino acid sequence or composition, but we show that a long segment of a viral protein can support infection independent of its sequence or composition. During virus entry, the papillomavirus L2 capsid protein protrudes through the endosome membrane into the cytoplasm to bind cellular factors such as retromer required for intracellular virus trafficking. Here, we show that an ~110 amino acid segment of L2 is predicted to be disordered and that large deletions in this segment abolish infectivity of HPV16 pseudoviruses by inhibiting cytoplasmic protrusion of L2, association with retromer, and proper virus trafficking. The activity of these mutants can be restored by insertion of protein segments with diverse sequences, compositions, and chemical properties, including scrambled amino acid sequences, a tandem array of a short sequence, and the intrinsically disordered region of an unrelated cellular protein. The infectivity of mutants with small in-frame deletions in this segment directly correlates with the size of the segment. These results indicate that the length of the disordered segment, not its sequence or composition, determines its activity during HPV16 pseudovirus infection. We propose that a minimal length of L2 is required for it to protrude far enough into the cytoplasm to bind cytoplasmic trafficking factors, but the sequence of this segment is largely irrelevant. Thus, protein segments can carry out complex biological functions such as Human papillomavirus pseudovirus infection in a sequence-independent manner. This finding has important implications for protein function and evolution. [ABSTRACT FROM AUTHOR]

The cottontail rabbit papillomavirus (CRPV)-associated VX2 carcinoma of the New Zealand White rabbit serves as a model system for human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to evaluate the tumor-inhibiting effect of RNAi-mediated knockdown of the CRPV oncogenes, E6 and E7, using siRNA-loaded lipopolyplexes (LPPs). VX2-carcinoma-derived cells were cultured for up to 150 passages. In addition, CRPV E6 and E7 oncogenes were transiently expressed in COS-7 cells. Efficiency and safety of LPPs were evaluated in both VX2 cells and the COS-7 cell line. Both of these in vitro CRPV systems were validated and characterized by fluorescence microscopy, Western blot, and RT-qPCR. Efficient knockdown of CRPV E6 and E7 was achieved in VX2 cells and COS-7 cells pretransfected with CRPV E6 and E7 expression vectors. Knockdown of CRPV oncogenes in VX2 cells resulted in reduced viability, migration, and proliferation and led to a G0/G1 block in the cell cycle. CRPV E6 and E7 siRNA-loaded LPPs could represent promising therapeutic agents serving as a paradigm for the treatment of papillomavirus-positive cancers and could be of value for the treatment of CRPV-associated diseases in the rabbit such as papillomas and cancers of the skin. [ABSTRACT FROM AUTHOR]

Background/Aim: The prevalence of human papillomavirus (HPV) in non-malignant tonsils can vary according to geographical location, age group, and risk factors. Some studies have found a relatively low prevalence of HPV, while other studies have found higher rates in non-malignant tonsils. The presence of HPV in non-malignant tonsils may be associated with precursor lesions that have the potential to develop into cancer. The aim of the current study was to detect the prevalence of HPV and p16 (one of the HPV types) in non-malignant tonsils and determine the existence of HPV in tonsil tissue using molecular and histological techniques. Methods: One hundred-three samples from non-malignant tonsils and one sample from squamous cell carcinoma of the tonsils were analyzed for the prevalence of HPV using molecular and histological methods. Real-time polymerase chain reaction (qPCR) was performed to detect HPV in the tissue samples. Results: HPV was not found in any tissue specimens based on histopathological and p16 immunohistochemical evaluations. HPV was not detected in all tissue samples using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Conclusions: In our study of one hundred and four patients, HPV and p16 were not genetically detected in the tonsils that underwent surgery for reasons other than cancer. Hence, more comprehensive studies can contribute to evaluating the relationship between benign tonsil tissue and HPV infection, potentially leading to improved diagnostic and preventative measures. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer has been recognized as an important health problem in women. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. The present study was conducted with aim to estimate the prevalence of genital HPV in suburban women. Methods: In this systematic and meta-analysis study from February 20 to March 20, 2023, databases of Web of Science, Scopus, PubMed and Embase and Google scholar search engine were searched without time restrictions using the keywords such as "papillomavirus", "genital wart" and "suburban population" and relevant synonyms. In the selection criteria, observational studies on the prevalence of genital papillomavirus in suburban women were included. Heterogeneity of the studies was evaluated with I2 and Cochran's Q test. Funnel plot and Egger & Begg tests were used to assess the publication bias of the studies. Results: Finally, 10 studies with a sample size of 65,813 remained in accordance with the purpose of our study. The results of the meta-analysis showed that the overall prevalence of HPV in suburban women was 17% (95% CI: 13-21%) and HPV/16 genotype with a prevalence of 18% (95% CI: 13-23%) was the most common genotype in the affected people. Conclusion: In general, the prevalence of genital papilloma virus infection was relatively high in suburban women. This result can be useful for policy makers in planning preventive strategies for cervical cancer in poor and low-income environments.

A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases.

Domestic dogs are currently recognized as being infected by 25 different canine papillomavirus (CPV) types classified into three genera. A short sequence from a novel CPV type was amplified, along with CPV1, from a papilloma (wart) from the mouth of a dog. The entire 7499 bp genome was amplified, and CPV26 contained putative coding regions that were predicted to produce four early proteins and two late ones. The ORF L1 showed less than 62% similarity for all previously sequenced CPV types but over 69% similarity to multiple Omegapapillomavirus types from a variety of Caniform species including the giant panda, Weddel seal, and polar bear. Phylogenetic analysis confirmed CPV26 clusters within the Omegapapillomavirus genus. Specific primers were used to investigate the presence of CPV26 DNA within a series of 37 canine proliferative lesions. CPV26 DNA was amplified from one lesion, a cutaneous papilloma that also contained CPV6. This is the first time a PV type within the Omegapapillomavirus genus has been detected in a non-domestic species and this provides evidence that the omegapapillomaviruses infected a common ancestor of, and then co-evolved with, the Caniform species. Whether CPV26 causes disease is uncertain, but the absence of an E7 protein may suggest low pathogenicity.