Papillomavirus Type Research Articles

The association between insulin-like growth factors I, II and bovine papillomavirus type-1 expressions in naturally occuring bovine fibropapilloma cases

In this study, we hypothesized that insulin-like growth factors (IGFs) may have a combine effect together with BPV-1 in the etiopathogenesis of fibropapilloma. With this aim, macroscopic and histopathological findings of the fibropapillomatous changes were described in masses collected from the skin of neck, hindlimbs and abdominal region of 15 cattle, ranging from 14 to 23 months old. In several cases, hyperkeratosis (n=7) and/or parakeratosis (n=8), acanthosis (n=15), degenerative changes (n=15) and inflammatory cell infiltrations (n=9), and also vascularization (n=15) were accompanied to the neoplastic cells comprising paranchyme and stroma. In terms of virus entity in collected samples, L1 and L2 genes of BPV-1 were found to be positive by PCR. Immunohistochemically, BPV-1, IGF-I and IGF II expressions were found parallel. IGF-I positivities were stronger and more common in the epidermal cells and connective tissue components when compared with IGF-II positivity. In general, immunolocalization of both IGF-I and IGF-II were seen in the cytoplasm and membranes of all cell layers in the epidermis and only in the fibrocytes and fibroblasts in addition to collagen bundles. We concluded that IGF-I and IGF-II could have an effect as much as BPV-1 in pathogenesis of fibropapillomatous changes in the epidermis and dermis

A Solanum incanum extract (SR-T100) regresses vulvar condyloma acuminatum and induces distinct autophagic and apoptotic responses in different types of HPV-infected cells

BackgroundThe Solanum species have been used for the treatment of warts, tumor and cancer in folk medicine. The S. incanum extract is an important traditional Chinese medicine in Taiwan since 1973. The purpose of the present study was to evaluate the efficacy and safety of Solanum incanum (synonym: Solanum undatum) extract (SR-T100), a water-soluble product primarily composed of alkaloid solamargine, for the treatment of human condyloma and to study the possible underlying anti-condyloma mechanisms.MethodsWe conducted a pilot study to test the effectiveness and side effects of SR-T100 gel (2.3% solamargine in Solanum incanum plant extract) for the treatment of external genital warts. We produced different types of human papillomavirus (HPV) E6/E7-infected cells by lentiviral technology and studied the differences in apoptosis and autophagy between these cells under the treatment of SR-T100.ResultsNineteen (73%) of 26 patients using the SR-T100 gel exhibited a response, and 16 (61.5%) patients achieved total clearance. Only one patient showed severe (grade 3-4) skin-related side effects. SR-T100 induced mitochondria-dependent apoptosis in HPV-infected cells. Cells expressing the high-risk HPV E6/E7 type were resistant to SR-T100-induced apoptosis. SR-T100 induced a greater autophagic response in HPV 16, 18-E6/E7 cells than in HPV 6b, 11-E6/E7 cells. Autophagy inhibition enhanced SR-T100-induced apoptosis in HPV 16, 18-E6/E7 cells, whereas apoptosis inhibition enhanced SR-T100-induced autophagy in HPV 6b, 11-E6/E7 cells.ConclusionsSR-T100 is effective for the treatment of human vulva condyloma, with few side effects. Compared with those with high-risk HPVs, cells with low-risk HPVs were more sensitive to SR-T100 treatment. Autophagy played a protective role in SR-T100-induced apoptosis in HPV-infected cells.Trial registrationNCT01676792; Registered: August 29, 2012 (retrospectively registered).

A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program.

Recurrent respiratory papillomatosis is a rare but morbid disease caused by human papillomavirus (HPV) types 6 and 11. Infection is preventable through HPV vaccination. Following an extensive quadrivalent HPV vaccination program (females 12-26 years in 2007-2009) in Australia, we established a method to monitor incidence and demographics of juvenile-onset recurrent respiratory papillomatosis (JORRP) cases. The Australian Paediatric Surveillance Unit undertakes surveillance of rare pediatric diseases by contacting practitioners monthly. We enrolled pediatric otorhinolaryngologists and offered HPV typing. We report findings for 5 years to end 2016. The average annual incidence rate was 0.07 per 100000. The largest number of cases was reported in the first year, with decreasing annual frequency thereafter. Rates declined from 0.16 per 100000 in 2012 to 0.02 per 100000 in 2016 (P = .034). Among the 15 incident cases (60% male), no mothers were vaccinated prepregnancy, 20% had maternal history of genital warts, and 60% were first born; 13/15 were born vaginally. Genotyped cases were HPV-6 (n = 4) or HPV-11 (n = 3). To our knowledge, this is the first report internationally documenting decline in JORRP incidence in children following a quadrivalent HPV vaccination program.

Cross-reactivity of antigens and antibodies belonging to different pathogenic types of human papillomaviruses.

The analysis of the properties of a quadrivalent peroral vaccine against the cervical cancer, which was created in a plant expression system on the base of transgenic tomato fruits, by immunoassay and Western blot hybridization showed that the antibodies against human papilloma virus 16 L1 (HPV16 L1) actively interacted not only with the antigenic proteins HPV18 L1, HPV31 L1, and HPV45 L1, but also with the antigenic protein HPV6 L1, which belongs to another HPV family. Thus, new data on the possibility of crossreactivity between antibodies and antigens belonging to remote HPV families were obtained.

Infections with Multiple High-risk Human Papillomavirus (HPV) Types are Associated with More High-grade Squamous Intraepithelial Lesions (HSIL) on Follow-up Cervical Biopsy

Infections with Multiple High-risk Human Papillomavirus (HPV) Types are Associated with More High-grade Squamous Intraepithelial Lesions (HSIL) on Follow-up Cervical Biopsy

Prevalence of human papillomavirus infection in squamous cell carcinoma of the anal canal in a Northeast City in Brazil: viral genotyping and clinical aspects

BackgroundAnal cancer malignancies comprise about 1.5 to 3% of cancers from the gastrointestinal in which high-risk types of human papillomavirus (HR-HPV) is responsible for >80% of cases. The aim of this work was to detect and perform human papillomavirus (HPV) genotyping in squamous cell carcinoma specimens from the anal canal and to investigate the association between viral infection and histopathological and clinical aspects.MethodsThe presence of genotype-specific HPV DNA in formalin-fixed paraffin embedded tissue from 27 anal SCC samples from a reference cancer hospital of São Luís, State of Maranhão, Brazil was performed by Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay. Fisher’s Exact test and Chi-square test were performed in order to evaluate the association between HPV type and clinical and morphological variables. P values less than 0.05 were considered statistically significant.ResultsAverage age of patients at the time of diagnosis was 54.96 years ± 15.81; 74.07% of patients were female. Vegetative ulcers represented the most common type of lesion (22.22%). The lesions ranged in size from 2.1 cm to 5.0 cm and mostly were well-differentiated (70.38%). Lymph node involvement was observed in 26% of the patients. Molecular evaluation revealed that HPV infection was detected in 81.48% of the lesions, and the most common type found was the oncogenic HPV 16. Statistical analysis indicated that the clinical and histopathological variables were not associated with HPV infection.ConclusionsOur results indicate that anal SCC rarely occurs in the absence of HPV and emphasize the predominant role of HPV16. The evaluation about genotype-specific prevalence of HPV in anal SCC is important to assess the potential benefit of HPV vaccination.

Human papillomavirus (HPV) type and prevalence in Pacific Islander cervical cancer patients

Human papillomavirus (HPV) type and prevalence in Pacific Islander cervical cancer patients

Host cell tropism, genome characterization, and evolutionary features of OaPV4, a novel Deltapapillomavirus identified in sheep fibropapilloma

Investigating papillomavirus (PV) diversity is crucial to fully comprehend pathogenicity, genetic features, and evolution of taxa hosted by domestic and wild animal species. This study reports the identification of OaPV4, a novel ovine PV type within Deltapapillomaviruses 3. The study of OaPV4 genomic features combined to in situ hybridization and immunohistochemistry investigations allowed extrapolating several general biological features of ovine PVs, such as their cellular tropism, pathogenicity, and evolutionary history. Based on results, ovine PVs can be grouped into a polyphyletic ancient group of viruses, which splits in two main subgroups having peculiar cellular tropism and pathogenicity. Results add up to animal PV diversity and are crucial to future studies aimed to investigate the correlation between animal PV and cutaneous benign and malign proliferations.

Efficient Production of Papillomavirus Gene Delivery Vectors in Defined In Vitro Reactions

Papillomavirus capsids can package a wide variety of nonviral DNA plasmids and deliver the packaged genetic material to cells, making them attractive candidates for targeted gene delivery vehicles. However, the papillomavirus vectors generated by current methods are unlikely to be suitable for clinical applications. We have developed a chemically defined, cell-free, papillomavirus-based vector production system that allows the incorporation of purified plasmid DNA (pseudogenome) into high-titer papillomavirus L1/L2 capsids. We investigated the incorporation of several DNA forms into a variety of different papillomavirus types, including human and animal types. Our results show that papillomavirus capsids can package and transduce linear or circular DNA under defined conditions. Packaging and transduction efficiencies were surprisingly variable across capsid types, DNA forms, and assembly reaction conditions. The pseudoviruses produced by these methods are sensitive to the same entry inhibitors as cell-derived pseudovirions, including neutralizing antibodies and heparin. The papillomavirus vector production systems developed in this study generated as high as 1011 infectious units/mg of L1. The pseudoviruses were infectious both in vitro and in vivo and should be compatible with good manufacturing practice (GMP) requirements.

Impact of HPV typing and p53 expression on radiosensitivity in patients with cervical cancer

Objective To investigate the association of human papilloma virus (HPV) typing and p53 expression with radiosensitivity in patients with cervical cancer. Methods A total of 80 patients with cervical cancer from 2014 to 2016 were enrolled, and among these patients, 40 had stage ⅠB+ ⅡA disease and 40 had stage ⅡB+ ⅢA disease. HPV genotype was identified and p53 expression was measured. All the patients underwent external and internal pelvic irradiation alone, and the correlation between short-term therapeutic effect and HPV typing/p53 expression was analyzed. The chi-square test or the Fisher′s exact test was used for statistical analysis, and Spearman rank correlation analysis was also performed. Results The radiotherapy-insensitive (stable disease+ progressive disease) group had higher p53 positive rates than the radiotherapy-sensitive (complete response+ partial response) group (stage ⅠB+ Ⅱ: 100% vs. 80.0%, P=0.044; stage ⅡB+ ⅢA: 100% vs. 90.0%, P=0.013). The expression of p53 was negatively correlated with radiosensitivity (r=-0.427, P=0.000). In the radiotherapy-insensitive group of patients with stage ⅠB+ Ⅱ and ⅡB+ ⅢA, the rate of HPV multiple infections was higher than that of single subtype infection (65.0%/95.0% vs. 35.0%/5.0%, P=0.004 and 0.003), while in the radiotherapy-sensitive group, the rate of single subtype infection was higher than that of multiple infections (85.0%/60.0% vs. 15.0%/40.0%, P=0.004 and 0.003). The highest detection rate of HPV16 was 66.3% in all patients, and the highest detection rate of HPV18 was 60.0% in the radiotherapy-insensitive group. Conclusions High expression of p53 is associated with radioresistance in patients with cervical cancer. Patients with HPV multiple infections have poor radiosensitivity, and HPV16 is the most common subtype in dual infection. Among patients who do not achieve remission after radiotherapy, HPV multiple infections with HPV18 as the main pathogen has the highest detection rate. Key words: Human papilloma virus; p53 gene; Cervical neopalsms/radiotherapy

CURRENT RECOMMENDATIONS REGARDING VACCINATION OF PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES

Background. Patients suffering from autoimmune inflammatory rheumatic diseases (AIIRD) are exposed to a higher risk of infections due to both their background and the immunosuppressant and immunomodulatory medications. This brings us to the question of what we can do to ensure the protection of our patients. And one of the answers should be vaccination. Methods. We performed a literature search in electronic database (PubMed) using keywords related to vaccination and rheumatic diseases. Also, relevant information concerning vaccination recommendations were collected form a website search of specific organizations dealing with management of autoimmune rheumatic disease in various countries. Results. Patients with AIIRD are at increased risk of infections and even if some of them could be prevented in part by vaccines, the rates of vaccination in this category of patients remains low. The 2015 American College of Rheumatology (ACR) guideline for the treatment of rheumatoid arthritis recommends the administration of influenza, pneumococcal, hepatitis B, human papilloma and shingles vaccines in patients requiring disease modifying antirheumatic drugs (DMARDs) or biologics, the first three being strongly recommended in patients with rheumatoid arthritis. The guideline does not recommend the administration of life attenuated vaccines, such as shingles vaccine, in patients under biologics. These are consistent with the recommendations from the Centers for Disease Control and Prevention (CDC) for vaccination of immunocompromised patients. In cases where live attenuated vaccines need to be used, the immunosuppressive therapy should be delayed by at least 4 weeks following vaccination. Conclusions. Despite important differences between different countries, there is a general consensus on the importance of immunizing AIIRD patients through vaccination. The most widely recommended vaccination regimens refer to influenza and pneumococcal vaccines, but other specific vaccines such as hepatitis B, human papilloma virus, herpes zoster, meningococcal, and Haemophilus influenzae type b should also be considered.

An age-structured model of the human papillomavirus dynamics and optimal vaccine control

We formulate an age-structured model based on a system of nonlinear partial differential equations to assist the early and catch up female vaccination programs for human papillomavirus (HPV) types 6 and 11. Since these HPV types do not induce permanent immunity, the model, which stratifies the population based on age and gender, has a susceptible-infectious-susceptible (SIS) structure. We calculate the effective reproduction number [Formula: see text] for the model and describe the local-asymptotic stability of the disease-free equilibrium using [Formula: see text]. We prove the existence of an endemic equilibrium for [Formula: see text] for the no vaccine case. However, analysis of the model for the vaccine case reveals that it undergoes the phenomenon of backward bifurcation. To support our theoretical results, we estimate the age and time solution with the given data for Toronto population, when an early and catch up female vaccine program is adopted, and when there is no vaccine. We show that early and catch up female vaccine program eliminates the infection in both male and female populations over a period of 30 years. Finally, we introduce the optimal control to an age-dependent model based on ordinary differential equations and solve it numerically to obtain the most cost-effective method for introducing the catch up vaccine into the population.

Complete Genome Sequence of a Novel Human Betapapillomavirus Isolated from a Skin Sample.

ABSTRACTWe report the genetic characterization of a new papillomavirus (HPV_MTS1) isolated and fully cloned from a skin swab. The L1 open reading frame of HPV_MTS1 was 85% identical to its closest human papillomavirus (HPV) type 80, which belongs to the species beta-2 of the genus Betapapillomavirus, hence qualifying it as a new HPV type.

Breadth of T Cell Responses After Immunization with Adenovirus Vectors Encoding Ancestral Antigens or Polyvalent Papillomavirus Antigens.

Oncogenic human papillomaviruses (HPVs) are in most cases eliminated by intervention of T cells. As many other pathogens, these oncogenic HPVs belong to an ancient and diverse virus family. Therefore, we found it relevant to investigate the potential and limitations of inducing a broad response-either by inducing cross-reactive T cells or by administering a polyvalent vaccine. To test these strategies, we designed three ancestral and two circulating sequences based on the two domains of the E1 and E2 proteins of papillomaviruses (PVs) that exhibit the highest degree of conservation in comparison with the other PV proteins. The PV sequences were fused to a T cell adjuvant, the murine invariant chain and encoded in a recombinant adenoviral vector which was administered to naïve outbred mice. By measuring T cell responses induced by these different vaccines and towards peptide pools representing three circulating strains and a putative ancestor of oncogenic HPVs, we showed that the ancestral vaccine antigen has to be approximately 90% identical to the circulating PVs before a marked drop of ~90% mean CD8+ T cell responses ensues. Interestingly, the combination of two or three type-specific PV vaccines did not induce a significant decrease in the CD8+ T cell response to the individual-targeted PV types. Polyvalent HPV vaccine based on the E1 and E2 proteins seem to be capable of triggering responses towards more than one type of PV while the cross-reactivity of ancestral vaccine seems insufficient in consideration of the sequence diversity between HPV types.

Multiplex Polymerase Chain Reaction for the Detection of High-risk-Human Papillomavirus Types in Formalin-fixed Paraffin-embedded Cervical Tissues

Detecting high-risk-human papillomavirus (HPV) types has become an integral part of the cervical cancer screening programmes. This study aimed to develop a multiplex polymerase chain reaction (PCR) for identification of HPV types 16 and 18 along with the beta globin gene in formalin-fixed and paraffin-embedded cervical biopsy specimens. A total of 59 samples from patients with cervical abnormalities were tested. HPV 16 positivity was 50% in cervical cancers and 52.9% in cervical intraepithelial neoplasia. Our multiplex PCR protocol can be used as a simple and cost-effective tool for high-risk-HPV detection in cervical cancer screening programmes.

Unusually high incidence of multifocal epithelial hyperplasia in children of the Nahuatl population of Mexico.

Multifocal epithelial hyperplasia is an uncommon disease of the oral mucosa caused by the human papilloma virus. To study the clinical and pathological findings of multifocal epithelial hyperplasia detected during an oral examination of 343 Mexican Nahuatl children from a single primary school in El Paso de Cupilco, Mexico. A thorough oral examination was performed in all children and clinical data (age, gender, location and number of lesions) were documented and analyzed. Multifocal epithelial hyperplasia was diagnosed in 110 of the 343 children (32.3%). The ages of the children varied from 5 to 15 years, and of these, 56.3% were girls. The lesions were asymptomatic, 0.2 to 3.0 cm in diameter, soft, round to oval, smooth surfaced, sessile papulonodules, similar in colour to that of the surrounding mucosa. The lesions were commonly seen on the buccal mucosa and tongue, and most affected children (85%) had less than 5 lesions. Children in the 7 to 10 years age group were most often affected. Human papillomavirus typing was not done owing to a lack of facilities. There is a high incidence of multifocal epithelial hyperplasia in Nahuatl children with a predilection for females.

Identification of canine papillomavirus by PCR in Greyhound dogs.

BackgroundCorns are hard protuberances that occur on the digital footpads of Greyhound dogs. The cause of these lesions is unknown and there is little information about them in the veterinary literature. We received anecdotal examples of dog to dog spread of corns suggesting an infectious cause. The aim of this study was to determine if papillomavirus (PV) is associated with Greyhound corns.MethodsWe examined four corns from two unrelated adult Greyhound dogs that resided in Florida and Washington, respectively, for PV by PCR. The samples were obtained by owner coring of two lesions from one dog and laser removal of two lesions from the other dog. Total nucleic acid was extracted and DNA was amplified using two PCR primer sets that have been shown to amplify a broad range of PVs from humans and animals: FAP59/ FAP64 and MY11/ MY09. The DNA sequences were compared with all sequences in GenBank. Formalin-fixed, paraffin-embedded tissue from the footpads of four dogs with other inflammatory dermatoses were also examined.ResultsPV DNA was amplified from all four corn lesions, while no PV DNA was amplified from other tissues. Comparison of the 444-bp sequences amplified by the MY11/ MY09 primers identified two different PVs. One showed 96% nucleotide sequence similarity with the L1 gene of canine PV type 12. The other showed 78% similarity to canine PV type 16 and, therefore, represents a novel PV. In one of the corns, infection by two of the identified PVs was found.DiscussionThese results suggest PV infection could be involved in the pathogenesis of corns in Greyhound dogs.

Correlation analysis of human papilloma virus variant intratumoral high-risk subtypes and cervical intraepithelial distribution

Objective To study the county high-risk women human papilloma virus (HPV) type distribution and subtypes of cervical intraepithelial neoplasia relevance, designed to provide a clinical risk assessment theoretical support. Methods 520 female patients with first visit high-risk HPV infection were selected.All subjects were HPV subtypes was measured and cervical intraepithelial neoplasia pathology, accounting analysis and correlation analysis and different subtypes of HPV accounting for patients with cervical lesions. Results 520 cases of HPV subtypes result patients showed that HPV infection subtypes, HPV16, HPV18, HPV31 and HPV58 infection higher proportion (44.8%, 19.2%, 11.5% and 16.7%), other types of infection was relatively low.520 cases of HPV infection in patients with CIN Ⅰ and CIN Ⅱ-Ⅲ and cervical squamous cell carcinoma was more, more than 15.0% of the total, a relatively small proportion of other types of cancer patients.In paragraph CIN Ⅱ-Ⅲ, HPV16 infection subtypes higher proportion of more than 60.0%, while the other was closer in cervical intraepithelial neoplasia, there was no difference between the written press and hold; in squamous cell carcinoma, accounting for HPV31 subtype only inferior HPV16(24.3%), which was significantly higher than the proportion of cervical adenocarcinoma(9.5%)(χ2=3.821, P=0.049). Conclusion HPV infection in patients with high-risk subtypes higher risk of cervical lesions, require special attention, neoplasia different risks in different subtypes of patients infected cervical epithelium, clinical research is worth attention. Key words: HPV subtypes; Cervical intraepithelial neoplasia; Correlation analysis

How many papillomavirus species can go undetected in papilloma lesions?

A co-infection comprising to at least seven papillomavirus (PV) types was detected by next generation sequencing (NGS) of randomly primed rolling circle amplification (RCA) products of a bovine (Bos taurus) papilloma lesion from the Brazilian Amazon region. Six putative new PV types that could not be detected by commonly used PCR protocols were identified. Their overall L1 nucleotide identities were less than 90% compared to described PV species and types. L1 nucleotide BLAST sequence hits showed that each new type was related to Beta, Gamma, Dyokappa, Dyoeta, and Xipapillomavirus, as well as two likely new unclassified genera. Our results show that the employment of NGS is relevant to the detection and characterization of distantly related PV and is of major importance in co-infection studies. This knowledge will help us understand the biology and pathogenesis of PV, as well as contribute to disease control. Moreover, we can also conclude that there are many unknown circulating PVs.

Dedicated researcher brings cancer care to rural communities

Dedicated researcher brings cancer care to rural communities