Presence Of Papillomavirus Research Articles

Spontaneous and post-interventional regression of cervical HPV infection.

Recent literature sources suggest that 15-20% of all malignant diseases have a viral aetiology. About 5% of these are caused by the human papillomavirus. The presence of papillomavirus is one of the strongest risk factors for development of a cervical pre-cancerous lesion and subsequent cervical cancer. The presented review provides a brief summary and characterisation of risk factors that influence spontaneous and post-interventional regression and persistence of papillomavirus in the cervical area.

Molecular detection of transcriptionally active ovine papillomaviruses in commercial equine semen.

Virological evaluation was performed on equine semen to detect the presence of papillomaviruses (PVs) using droplet digital polymerase chain reaction (ddPCR) as the aim of this study was to investigate whether the sperm from asymptomatic stallions harbors ovine papillomaviruses (OaPVs). Twenty-seven semen samples were analyzed, 18 of which were commercially acquired. The remaining nine samples comprising semen and peripheral blood, were collected from nine stallions with no apparent signs of PV-related diseases during clinical examination at the Didactic Veterinary University Hospital (DVUH) of Naples. OaPV was detected in 26 semen samples. OaPV1 was the most prevalent virus infecting equine semen. OaPV1 infected 21 semen samples (~80.8%) and showed a high number of DNA and RNA copies per microliter. qPCR was used to detect OaPV1 DNA in the 18 semen samples. ddPCR was used to detect and quantify the expression of OaPV2, OaPV3, and OaPV4. qPCR failed to detect DNA for these genotypes. Additionally, ddPCR was used to detect the transcriptionally active OaPV1 in six blood and semen samples from the same stallion. ddPCR failed to detect any nucleic acids in OaPVs in peripheral blood samples from the three stallions. In one semen sample, ddPCR detected OaPV1 DNA but failed to detect any nucleic acid in the remaining two semen samples, and peripheral blood from the same animals of the remaining 18 semen samples was not available, OaPV1 and OaPV4 were responsible for nine and five single infections, respectively. No single infections with either OaPV3 or OaPV4 were seen.

Clinical errors in the diagnostic of cervical dysplasia. Clinical cases

Introduction: The cervical screening goal is to detect and treat precancers before cancer. We wanted to understand why errors in the clinical diagnostic and management of patients with persistence of human papillomavirus (HPV); infection occur in gynecological practice. Aim: Aim of the study was to evaluate 3 clinically important complications of situations for women aged 18-45 years. The study aimed to assess the diagnostic accuracy by colposcopy visualization, cytology and biopsy results, and presence of HPV infection. We aimed to analyze the false-negative (FN) cytology diagnoses inpatients with presence of HPV, colposcopy visualization, histologically proven cervical intraepithelial neoplasia (CIN) 2-3. Material and Methods: A retrospective analysis of errors in the management of patients was carried out, in treatment methods, especially with the use of cryodestruction, colposcopy pictures, results of cytological and histological conclusion, results of examination for oncogenic types of papillomavirus were presented. Discussion: After analyzing all errors in the management of patients with persistence of papillomavirus and preliminary cryotherapy of the cervix, the main reasons that led to the progression of the disease up to cervical cancer were noted. Conclusion: In the presence of papillomavirus, cryodestruction of the cervix is not advisable, even if no cervical dysplasia was detected by histological conclusions.

The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.

The role of the vulvar microbiome in the development of (pre)malignant vulvar disease is scarcely investigated. The aim of this exploratory study was to analyze vulvar microbiome composition in lichen sclerosus (LS) and vulvar high-grade squamous intraepithelial lesions (HSIL) compared to healthy controls. Women with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements. Healthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043). This study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.

Low presence of papillomavirus and its lack of correlation with clinicopathological factors in breast cancer: a case control study.

Breast cancer is currently the most commonly diagnosed neoplasm in women worldwide. There is evidence that human papillomavirus (HPV) infection may play a key role in breast cancer aggressiveness, but results are conflicting across studies. The aim of this study was to investigate the presence of the HPV viral genome in benign and malignant breast tissue samples and its clinicopathological characteristics of cancer. In this case-control study, 100 formalin-fixed paraffin-embedded (FFPE) of breast cancer and 100 blocks of non-cancerous breast tissue were selected as a control group from the pathology department of Imam Khomeini Hospital in Ahvaz from 2020-2022. The presence of HPV was detected using nested PCR including MY09/11 primers and sequencing were performed for virus genotyping. The present study enrolled 100 subjects each in two cancer and control groups with a mean age of 52.81±13.23 and 35.77±11.65, respectively. The risk of cancer in HPV-infected patients is almost 5 times higher than in HPV-negative individuals, it is not statistically significant (OR =4.99, 95% CI 0.35 to 72.15, p=0.238). The prevalence of HPV in the cancer and control groups was 7% and 1%, respectively and HPVs detected in two groups were of the HPV 16 genotype. Although the chance of ER and PR expression, lymphvascular involvement, perineural invasion, and higher tumor grade was higher in HPV-positive subjects than in HPV-negative subjects, this was not statistically significant (OR>1, p>0.05). Based on studies reporting the existence of sequences of different high-risk HPV types (oncogenes) in breast cancer tissues, this study confirmed the hypothesis of a possible infectious cause in the development of breast cancer. So far, however, the results have been controversial and inconclusive. Further studies with large sample sizes are needed to demonstrate the link between HPV and breast cancer.

Novel equid papillomavirus from domestic donkey.

Papillomaviruses can be of great medical importance as they infect humans and animals such as Equus species, other livestock and pets. They are responsible for several papillomas and benign tumours in their host. To describe a novel equid papillomavirus detected in oral swab samples collected from donkeys (Equus asinus) found on the Northwest plateau of China. Cross-sectional. Swab samples collected from the oral mucosa of 32 donkeys in the Gansu Province of China, were subjected to viral metagenomic analysis to detect the presence of Papillomavirus. After de novo assembly, a novel papillomavirus genome designated as Equus asinus papillomavirus 3 (EaPV3) was identified in the studied samples. Additional bioinformatic analysis of the assembled genome was done using the Geneious prime software (version 2022.0.2). The complete circular genome of EaPV3 is 7430 bp in length with a GC content of 50.8%. The genome was predicted to contain five ORFs coding for three early proteins (E7, E1, and E2) and two late proteins (L1 and L2). Phylogenic analysis of the nucleotide sequences of the concatenated amino acid sequences of the E1E2L1L2 genes revealed that EaPV3 is most closely related to Equus asinus papillomavirus 1 (EaPV1). The genome analysis of EaPV3 revealed similar genome organisation with other equine papillomavirus and the presence of E7 papillomavirus oncoprotein. Since there were no warts in the oral cavity of the donkeys in this study, and no biopsy samples taken, we are unable to conclusively link the novel virus to any clinical condition in the donkeys. The Comparative characterisation of EaPV3 and its closest relatives, as well as phylogenetic analysis demonstrated that it is a novel virus specie that clusters within the Dyochipapilloma PV genus.

Human papilloma virus presence and its physical status in primary pterygium

Pterygium is one of the most frequent pathologies in ophthalmology, and is a benign, overgrowth of fibrovascular tissue, often with a wing-like appearance, from the conjunctiva over the cornea. It is composed of an epithelium and highly vascular, sub-epithelial, loose connective tissue. There is much debate surround the pathogenesis of pterygium and a number of theories have been put forward including genetic instability, cellular proliferation, inflammatory influence, and degeneration of connective tissue, angiogenesis, aberrant apoptosis and viral infection. At present, the involvement of human papillomavirus (HPV) in the genesis of pterygium is controversial, as have reported that HPV is present in 58% of cases, while others have failed to detect HPV in pterygium. In this study, we evaluated the presence and viral genotype of HPV DNA in pterygia and healthy conjunctiva sample, and virus integration into the cellular genome.Forty primary pterygia samples and 12 healthy conjunctiva samples were analyzed to HPV DNA presence by polymerase chain reaction, using MY09/MY11 primers of HPV-L1 gene. Viral genotype was identified by DNA sequence analysis of this amplicon. HPV integration into the cellular genome was analyzed by western blot detecting HPV-L1 capsid protein.Presence of HPV was observed in 19 of the 40 pterygia samples. In contrast, healthy conjunctiva samples were negative. To determine virus type, sequence analyses were performed. Interestingly, 11 out of the 19-pterygium samples were identified as HPV-11 type, meanwhile, the remaining 8 pterygium samples were identified as HPV-18. HPV-L1 capsid protein were found only in 3 out of the 10 samples studied.In conclusion, our study identified the presence of HPV DNA exclusively in pterygium samples and described HPV-11 and -18 genotypes. Our results suggest that HPV may be involved in the pathogenesis of pterygium. On the other hand, the expression of the L1-HPV protein suggests viral integration into the cellular genome.

Searching bovine papillomavirus presence in lesions seen on teats of cows

The samples were taken from 106 cows with various-looking lesions on their teats and ranged in age from 2 to 8 years. Enzyme-linked immunosorbent assay (ELISA) antigen (Ag) positive for the bovine papillomavirus (BPV) was found in 59 (55.7%) blood serum samples. PCR using FAP59/64 primers was positive for 24 (22.6%) samples. BPV-2 (40, 37.7%), BPV-6 (28, 26.4%), BPV-8 (30, 28.3%), BPV-9 (36, 34%), BPV-10 (32, 30.3%), and BPV-12 (22, 20.8%) were found in a PCR type-specific analysis of single and mixed type teat warts. The highest positivity was observed in BPV-2, BPV-9 and BPV-10 in flat and round forms, BPV-6, BPV-10, BPV-12, and mixed types in rice grain-cauliflower forms, BPV-9 and mixed types in filiform in the distribution of types based on the macroscopic appearance of teat lesions. As for the distribution of BPV types according to age, the most BPV-2 types were found in the age group of two years, the most BPV-10 types in the age group of three years, the most BPV-9 types in the age group of four years, the most BPV-8+BPV-12 types in the age group of five years, and the most mixed types between the ages of six and eight years. The existence of the virus was then checked using electron microscopy on the chosen samples (at least one investigation was conducted), and it was positively identified using BPV type-specific primers. The authors concluded that BPV detection using an ELISA (Ag) test from blood serum samples was shown to be less sensitive than BPV type-specific PCR from wart samples.

Unraveling the Risk Factors and Etiology of the Canine Oral Mucosal Melanoma: Results of an Epidemiological Questionnaire, Oral Microbiome Analysis and Investigation of Papillomavirus Infection

Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study was conducted in 15 dogs with OMM and 15 paired controls whose owners answered an epidemiological questionnaire. Oral swabs from the same dogs were subjected to 16S rRNA sequencing for microbiome analyses. In addition, DNA fragments of OMM had their DNA extracted and amplified by polymerase chain reaction in an attempt to detect canine papillomaviruses. The gingiva was the most frequent anatomical site (47%) of OMM, and most tumors were stage III when diagnosed. Most dogs bearing OMM and the controls had grade 3 periodontal disease, and this factor, along with tartar treatment and tooth brushing, did not differ between cases and controls. Most dogs with OMM and most controls had contact with smokers; there was no statistically significant difference. Canine papillomaviruses were not detected among OMM cases. Tannerella forsythia and Porphyromonas gingivalis were significantly increased in case dogs compared to the controls. As these bacteria are reportedly involved in the pathogenesis of periodontal disease and esophageal cancer in humans, we suggest that they might be risk factors for the development of canine OMM. The limitations of this study include the low number of dogs, and therefore, further studies on canine OMM with larger numbers of animals are encouraged.

Coinfection of torque teno virus (TTV) and human papillomavirus (HPV) in cervical samples of women living in Tehran, Iran.

Background and Objectives:Torque Teno virus or transfusion-transmitted virus (TTV) is a non-enveloped virus with a single strand circular DNA genome that currently is classified in the Alphatorquevirus genus and the family of Anelloviridae. Unlike other DNA viruses, TTV has an extremely wide genomic diversity. This virus, based on previous studies, infects both healthy people, as well as those who have HCV and human papillomavirus (HPV). This study aimed to evaluate the coinfection of torque teno virus (TTV) and HPV in cervical samples from Iranian women.Materials and Methods:In this case-control study, the fresh cervical cytobrush specimens were collected from 150 women referred to Dena laboratory in Tehran. Viral DNA was extracted from samples. The HPV-DNA was detected and genotyped. Then, nested polymerase chain reaction (Nested PCR) was performed for TTV using specific primers.Results:Among 50 cervical specimens without HPV, 14 were TTV positive (28%); among 50 low-risk HPV cervical specimen, 23 were TTV positive (46%), and from 50 high-risk HPV cervical specimen, 48 were TTV positive (96%). There is a significantly higher prevalence of TTV virus in low-risk and high-risk papillomavirus-infected specimens than in healthy specimens (p 0.0001). Additionally, TTV is more prevalent in samples containing high-risk papillomaviruses than in samples with low-risk papillomaviruses (P = 0.048).Conclusion:The higher prevalence of TTV among people infected with papillomavirus than in non-infected people indicates that both viruses are transmitted by the same mechanism (sexual route). In addition, the prevalence of TTV in samples containing high-risk papillomavirus is significantly higher than that in samples containing low-risk papillomavirus. The presence of papillomaviruses, particularly high-risk types, may be associated with TTV proliferation, which requires further research in the future.

Association of human papillomavirus (HPV) infection and potentially pathogenic vaginal microorganisms in women attending at primary care nursing gynecological consultation

To identify the incidence of human papillomavirus (HPV) with the presence of other microorganisms. This is a cross-sectional study composed of 128 women who were attended in the basic health units, between 2014 and 2018, to perform the Pap smear. The presence of papillomavirus was investigated using conventional PCR with primers MY09/11 and GP5 +/6+ (echo and endocervix cells) and the smear bacterioscopy of vaginal secretions was performed to identify the microorganisms. Statistical was performed using the square test, including a risk ratio or 95% confidence interval. HPV infection was identified in 48.4% (n = 62) women. Corynebacterium sp (39.8%) was the most prevalent microorganism, followed by Escherichia coli (21.1%), Staphylococcus aureus (14.0%), Gardnerella vaginalis (13.2%) and Candida albicans (7%), respectively. According to statistical analysis or HPV and the group of potentially pathogenic microorganisms had a significant association p <0.02. Corynebacterium sp showed an effective protection (0.356 [0.170-0.744] <0.05) in relation to sociodemographic, gynecological and obstetric factors. Only vaginal discharge and pH had p <0.05 when comparing the presence of infection. The other variables showed no statistical differences. This study revealed an association between the presence of pathogenic microorganisms with HPV virus infection, confirming a need for a better understanding of the female genitals’ microbiota. Thus, research involving the vaginal infectious agents, methods of protection and rapid diagnosis to contribute to the reduction of the number of lesions in the cervix and cervical cancer are needed.

PD-L1 expression in sebaceous carcinomas.

Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

Papillomavirus DNA not detected in canine lobular orbital adenoma and normal conjunctival tissue

BackgroundCanine lobular orbital adenomas are benign tumors that arise from orbital glandular tissue and extend into the orbit, conjunctiva, and third eyelid. Surgical excision is challenging and recurrence rates are high following excision alone. Enucleation and exenteration reduces the likelihood of recurrence, but is a radical therapeutic option for an otherwise visual and comfortable eye. Human papillomavirus causes 4.5% of worldwide cancers in people and has been identified in up to 23% of benign salivary gland tumors. To date, the etiology of canine lobular orbital adenomas has not been established and it is reasonable to consider canine papillomaviruses as an associative agent with benign glandular tumors in dogs. Identification of the underlying etiology of these tumors may help establish treatment or preventative measures. The purpose of this study was to evaluate conjunctival and orbital tissue of phenotypically normal dogs and tissue from canine lobular orbital adenomas for the presence of papillomavirus DNA.ResultsThirty seven canine lobular orbital adenoma samples (36 formalin fixed paraffin embedded (FFPE) tissue samples from 33 dogs and one freshly collected sample) were evaluated via polymerase chain reaction for the presence of papillomavirus DNA. Conjunctival tissue samples, from 10 dogs with normal ocular examinations, excised immediately following euthanasia, were used as phenotypically normal controls. Three FFPE and one freshly collected tissue samples previously confirmed to be positive for papillomavirus DNA were used as positive controls. PCR products verified positive controls. Papillomavirus DNA was not detected in fresh conjunctival tissue of the phenotypically normal control dogs or in samples of fresh or FFPE canine lobular orbital adenoma tissue.ConclusionsAn association between papillomavirus and the development of canine lobular orbital adenomas is unlikely. Further research is needed to evaluate if other viruses play a role in the pathogenesis of canine lobular orbital adenomas.

Incidence trends for upper aerodigestive tract cancers in rural United States counties.

Recent declines in cancer incidence and mortality have not been distributed equally across the United States. Factors such as tobacco cessation and human papillomavirus presence might differentially affect urban and rural portions of the country. We used the Surveillance, Epidemiology, and End Results database to assess cancer incidence rates and trends from 1973 to 2015. We compared incidence rates for oral cavity, oropharynx, and larynx cancer in urban and rural counties and identified trends using Joinpoint software. Incidence of larynx and oral cavity cancer are decreasing faster in urban areas than in rural areas, while incidence of oropharynx cancer is increasing faster in rural areas than urban areas. Relative trends in incidence of larynx, oral cavity, and oropharynx cancer over the past 40 years are unfavorable for rural United States counties compared with urban areas. Cancer control programs should take this into account.

Loss of ZNF516 protein expression is related with HR-HPV infection and cervical preneoplastic lesions.

Cervical cancer is an important health issue among women worldwide. Cervical smear and human papillomavirus detection are the most used screening methods to detect preneoplastic and neoplastic lesions. However, as neither can predict cervical development, new markers are needed for this disease. ZNF516, a potential tumor suppressor gene, has been found altered in cervical cancer. The objective of this study was to determine ZNF516 immunohistochemistry frequency in cervical biopsies and its association with clinicopathological parameters, to evaluate its potential as marker in cervical lesions. A retrospective series of 452 formalin-fixed, paraffin-embedded (FFPE) cervical biopsies, obtained between 2002 and 2007, were selected for immunohistochemistry of ZNF516, p16 and Ki-67 markers. Human papillomavirus genotyping was performed on 272 of these samples through reverse line blot assay. An inverse relation between ZNF516 expression and cervical lesions grade (P < 0.001) was observed, given this protein was found mainly expressed in normal tissues, while was decreased in cervical lesions. As expected, the proliferation markers p16 and Ki-67 were found highly expressed in cervical cancer compared to normal tissues, and inversely correlated to ZNF516 expression (P < 0.01). High oncogenic risk-Human papillomavirus presence also was related to the lack of ZNF516 expression in cervical lesions (P < 0.05), and the detection of these two parameters showed a high sensitivity (70.9%) for preneoplastic lesions detection. The loss of ZNF516 expression was found in cervical lesions, and its detection potentially could be used as a complementary marker of early diagnosis in cervical lesions.

Erratum: The association between human papillomavirus presence and epidermal growth factor receptor mutations in Asian patients with non-small cell lung cancer.

[This corrects the article DOI: 10.21037/tlcr.2018.03.16.].

The association between human papillomavirus presence and epidermal growth factor receptor mutations in Asian patients with non-small cell lung cancer.

The etiology of non-small cell lung cancer (NSCLC) in non-smoker patients remains largely unknown. It has been widely proved that human papillomavirus (HPV) participates in the development of various cancers. Epidermal growth factor receptor (EGFR) mutation patients represent a large portion of non-smokers with NSCLC. We performed this meta-analysis to determine whether HPV infection in NSCLC tissue is associated with EGFR mutations compared with HPV negative controls. Online databases were searched up to June 30th 2017. We included studies in which HPV detection was based on polymerase chain reaction (PCR) methods. Random effects model was used in data synthesis and the relative effects were presented as odds ratio (OR) with 95% confidence intervals (CIs). Finally, four eligible studies with a total of 498 patients from Asian countries were identified and included. The general EFGR mutation positive rate was 38.2% among all patients, and the HPV DNA detection rate (HPV subtype being involved: 16, 18, 33 and 58) was 35.3%. The presence of EGFR mutation was significantly higher in HPV-positive patients compared with HPV-negative controls (52% vs. 31%; OR =2.41, 95% CI: 1.21 to 4.77; P=0.012), with moderate heterogeneity among studies (I2=59%; P=0.062). Our results suggest that HPV infection is associated with EGFR mutations in NSCLC, at least in Asian populations. Further efforts should be made on exploring the potential mechanism and the prognostic character of HPV/EGFR positive NSCLC patient.

Identification of Head and Neck Cancer Subtypes Based on Human Papillomavirus Presence and E2F-Regulated Gene Expression.

Human papillomavirus (HPV) is present in a subset of head and neck squamous cell carcinomas (HNSCCs). The cell cycle regulatory Rb-E2F pathway is a major target of HPV and is perturbed by these viruses in cell culture and animal models, as well as in human tumors. In this study, we examined differences in the Rb-E2F pathway displayed by HPV-positive (HPV+) and HPV-negative (HPV-) HNSCC tumors. We created a computational approach that effectively categorizes gene expression as unchanged, downregulated, or upregulated by comparing the gene's mRNA levels in the tumor to the corresponding mRNA levels across normal tissue samples. Our findings suggest that there are three major HNSCC subtypes, defined by differences in the presence of HPV and in E2F-regulated gene expression. Most HPV+ HNSCC tumors show upregulation of E2F-regulated genes, which is consistent with inactivation of Rb by the virus-encoded E7 protein. In contrast, many HPV- HNSCCs show little or no change in the Rb-E2F pathway. However, we also identified a set of tumors that show alterations in the Rb-E2F pathway in the absence of HPV. Thus, one class of HPV- HNSCCs arise without significant alterations of the Rb-E2F pathway, while a second class of tumors appear to deregulate this pathway independently of the presence of HPV. IMPORTANCE Cancer is a complex disease that can be caused by a multitude of factors. HNSCC is complicated because some of these cancers are clearly associated with HPV, while others have no viral involvement. Determining the pathways that are commonly altered in both types of HNSCC, as well as those that are unique to viral and nonviral tumors, is important for a basic understanding of how these cancers arise and progress and critical to the development of targeted therapies. In this work, we show that all HPV-associated tumors have increased expression of E2F target genes, indicating that the tumor suppressor function of Rb is blocked. Importantly, Rb is also inhibited in a subset of nonviral tumors, suggesting that mutations present in these cancers mimic the action of the HPV E6 and E7 oncogenes.

Tongue Squamous Cell Carcinoma in a European Lynx (Lynx Lynx): Papillomavirus Infection and Histologic Analysis.

Oral squamous cell carcinoma (SCC) is a common finding in domestic and wild felids. Only two cases of oral SCC have been reported in Lynx species (Lynx rufus and Lynx canadensis), at mandibular and gingival sites. In this study, we describe the first report of tongue SCC in a 15 years old female European lynx (Lynx lynx), along with viral investigations. Necropsy and histological analysis were performed and the presence of papillomavirus (PV) infection was investigated by ultrastructural and molecular methods. The lardaceous mass at tongue level was histologically diagnosed as moderately differentiated SCC. Typical microscopical features of SCC were also found in the retropharyngeal lymph node and at the pulmonary level. Neither viral DNA by PCR, nor viral particles by transmission electron microscopy were found. Despite that PV infection is associated with Felidae, this work reports the first description of tongue SCC in Lynx species, but no evidence of PV infection, suggesting that PV may not be involved in development of SCC in bobcat species.

Detection of human papillomavirus in oral mucosa

Introduction: According to the National Cancer Institute (INCA) 2017, Brazil shows high prevalence rates in malignant neoplasms with primary localization in the oral cavity, since oral cancer affects the lips and oral cavity. It is a multifactorial disease, derived from genetic, environmental or infectious factors (viruses) isolated or in association, causing cytogenetic changes that proceed through a somatic mutation sequence, resulting in uncontrolled cell proliferation. Objective: To study the detection of human papillomavirus (HPV) in the oral mucosa, making it possible to trace possible risk factors associated with its development. Methods: This is a descriptive cross-sectional study of the bibliographic review on the subject, monographs, dissertations, theses and books, comparatively analyzing the information from these research sources, making a discussion about the results of this survey. Results and Discussion: There are more than 100 types of papillomavirus identified, 24 of these related to the oral cavity. Transmission of papillomavirus to oral mucosa occurs by self-inoculation and through the practice of oral sex. Papillomavirus infection begins when the virus contacts the basal epithelial cells by a slow process of endocytosis, from the binding to a specific receptor on the surface of basal cells. Viral tropism is caused in part by the binding of specific viral surface proteins to certain host cell surface receptor proteins. Studies to detect the presence of papillomavirus in the oral mucosa reveal that this virus appears to persistently or frequently infect the mouth, including in children and adolescents. Conclusion: Detection rates vary mainly according to the population studied and the sensitivity of the methods used, with the main types of papillomavirus being found, Papillomavirus 16 and 18.