Presence Of Papillomavirus DNA Research Articles

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.

Bovine upper alimentary squamous cell carcinoma associated with bracken fern poisoning: Clinical-pathological aspects and etiopathogenesis of 100 cases.

Upper digestive tract (UDT) cancer is rare in cattle, however in Southern Brazil, the UDT squamous cell carcinomas (SCCs) are relatively common and have been associated with bracken fern consumption and the presence of papillomas. Although a theory of pathogenesis considers bovine papillomavirus type 4 (BPV-4) as a cofactor in the development of these SCCs, some aspects of the etiopathogenesis of this disease need to be more investigated. In fact, detection of BPV-4 in UDT papillomas is scarce in other regions of the world and has not been performed in Brazil. Therefore, this study had two aims: 1) to analyze the epidemiological, clinical and pathological aspects of 100 natural cases of SCCs in the UDT of cattle grazing on bracken fern (Pteridium arachnoideum) highly contaminated areas, investigating the associations between these parameters; and 2) to investigate the presence of papillomavirus DNA by polymerase chain reaction (PCR) in the UDT papillomas (n = 47) from 30 cattle that also had UDT SCCs. There were statistically significant associations between clinical signs and tumor localization in the UDT; between histological grade of differentiation and tumor localization; and a trend towards significant association between histological grade of differentiation and presence of metastases. The average age of cattle with oropharyngeal SCCs was 7.39 years, with statistically significant difference comparing to cattle with esophageal SCCs (8.6 years). No statistical association was observed among other clinical-pathological parameters (growth pattern and primary site of the tumor) analyzed. No BPV DNA was detected in papillomas by PCR. Therefore, these results suggest the possibility that papillomas of the UDT are not necessarily associated with BPV infection.

Congenitale cutane fibropapillomatose bij een warmbloedveulen

In deze casuïstiek wordt een zeldzaam geval van een congenitaal fibropapilloma op het voorhoofd van een warmbloedveulen beschreven. Chirurgische excisie van de massa was succesvol en na negen maanden nog steeds zonder recidief. Er werden geen andere abnormaliteiten bij het veulen vastgesteld. Morfologisch gezien betreft het letsel een fibro-epitheliaal type hamartoma van de huid. De fibreuze component werd tot dusver enkel bij varkens beschreven. Alhoewel bij volwassen dieren fibropapilloma’s vaak voorkomen en geassocieerd zijn met papillomavirusinfecties, werd zowel bij veulens als biggen voor de congenitale fibropapilloma’s nog geen virale oorzaak aangetoond. Ook in deze casus waren geen histopathologische indicaties voor infectie met papillomavirus en kon evenmin de aanwezigheid van papillomavirus-DNA aangetoond worden met PCR.

Human Papillomavirus Prevalence in Invasive Penile Cancer and Association with Clinical Outcome

The incidence of penile cancer is increasing, and is suggested to be explained by changes in sexual practice and increased exposure of men to sexually transmitted high risk human papillomavirus infection. In penile cancers from a Dutch population treated in 1963 to 2001 we found a high risk human papillomavirus prevalence of about 30%. In this study we assessed the prevalence of high risk human papillomavirus-DNA in a more recent, contemporary penile cancer cohort and its association with patient survival. High risk human papillomavirus-DNA presence was assessed by GP5+6+ polymerase chain reaction in 212 formalin fixed, paraffin embedded invasive penile tumor specimens of patients treated between 2001 and 2009. The 5-year disease specific survival was calculated using the Kaplan-Meier method with the log rank test and Cox regression. High risk human papillomavirus-DNA was detected in a subset of penile cancer cases (25%, 95% CI 19-31). HPV16 was the predominant type, representing 79% (42 of 53) of all high risk human papillomavirus infections. The 5-year disease specific survival in the high risk human papillomavirus negative group and the high risk human papillomavirus positive group was 82% and 96%, respectively (log rank test p=0.016). Adjusted for stage, grade, lymphovascular invasion and age, human papillomavirus status was still prognostic for disease specific survival (p=0.030) with a hazard ratio of 0.2 (95% CI 0.1-0.9). High risk human papillomavirus-DNA was observed in a quarter of penile cancer cases. No relevant increase in high risk human papillomavirus prevalence in recent decades was observed. The presence of high risk human papillomavirus-DNA in penile cancer confers a survival advantage.

The Presence of p16CDKN2A Protein Immunostaining Within Feline Nasal Planum Squamous Cell Carcinomas Is Associated With an Increased Survival Time and the Presence of Papillomaviral DNA

In humans, oral SCCs are either caused by papillomavirus (PV) infection or by other carcinogens such as tobacco. As these 2 groups of SCCs have different causes they also have different clinical behaviors. Immunostaining using anti-p16(CDKN2A) protein (p16) antibodies is used to indicate a PV etiology in human oral SCCs and p16-positive SCCs have a more favorable prognosis. The present study investigated whether p16 immunostaining within feline nasal planum SCCs was similarly associated with the presence of PV DNA and with a longer survival time. Intense p16 immunostaining was visible in 32 of 51 (63%) SCCs. In 30 cats with nonexcised SCCs, cats with p16-positive neoplasms had a longer estimated mean survival time (643 days) than cats with p16-negative SCCs (217 days, P = .013). Papillomavirus DNA was amplified more frequently from p16-positive nasal planum SCCs (28 of 32) than p16-negative SCCs (5 of 19, P < .001). The different survival times in cats with p16-positive and p16-negative SCCs suggests that p16 could be a useful prognostic indicator in these common feline cancers. As the clinical behavior of the SCCs can be subdivided using p16 immunostaining, the 2 groups of SCCs may be caused by different factors, supporting a PV etiology in a proportion of feline nasal planum SCCs.

Lymph node human papillomavirus DNA positivity in uterine cervical cancers and its relationship with prognostic factors.

Uterine cervical cancer is a major health care issue worldwide. Human papillomavirus (HPV) DNA positivity in regional lymph nodes has been proposed as a risk factor for recurrence in a number of studies. The aim of our study was to determine the correlation between well-known prognostic factors and HPV DNA positivity in regional lymph nodes of patients with cervical cancer who were treated surgically. Thirty-seven patients who underwent radical hysterectomy (Piver class III) with regional lymph node dissection for International Federation of Gynecology and Obstetrics stage IB uterine cervical cancer were assessed for nodal HPV DNA status using polymerase chain reaction. Human papillomavirus DNA presence and types were analyzed in paraffin-embedded tissues from all primary tumors and 746 regional lymph nodes. The correlation between HPV DNA positivity of the lymph nodes and prognostic factors (stage at the time of diagnosis, status of the regional nodes, status of parametrial and surgical margins, tumor size, histological type, cervical stromal invasion depth, and lymphovascular space invasion was investigated. Lymph node HPV DNA positivity increased in larger tumors (P < 0.05). In addition, lymph node metastasis and primary tumor HPV DNA status were closely correlated with the HPV DNA status of the lymph nodes (P < 0.05). Human papillomavirus DNA presence in the lymph nodes of patients with uterine cervical cancer may have an influence on disease survival and requires further research. Future studies with prospective design and large sample sizes using fresh operative specimens and quantitative HPV DNA detection methods are needed.

Human Papillomavirus DNA Presence in Pelvic Lymph Nodes in Cervical Cancer

This work intends to present a systematic overview of data that have been published so far with regard to methods used for tissue sampling and DNA testing and with regard to the prevalence of human papillomavirus (HPV) DNA in pelvic lymph nodes (LNs) and its prognostic significance. The HPV DNA status of LN in women with cervical cancer is being explored as a potential marker of "occult" metastases. Although the presence of HPV DNA in LN usually correlates with its metastatic involvement, there is always a subgroup of HPV-positive but histologically negative LNs. The significance of HPV in negative LNs remains uncertain, although several studies have concluded that HPV is a risk factor of recurrence. A small group size and a short follow-up are the main limitations for drawing any conclusion concerning prognostic significance of the presence of HPV DNA in LNs.

Detection of Canine Oral Papillomavirus DNA in Conjunctival Epithelial Hyperplastic Lesions of Three Dogs

Papillomavirus infections are responsible for plaques and papillomas in various locations on the skin and in mucous membranes. The aim of this report was to describe morphologic features of a viral pigmented conjunctival plaque and 2 conjunctival squamous papillomas in 3 dogs, and to investigate these lesions for the presence of papillomavirus DNA by polymerase chain reaction (PCR), DNA sequence analysis, and in situ hydridization (ISH). Histopathology revealed in all neoplasms various degrees of epithelial hyperplasia, acanthosis, and hyperkeratosis with koilocytosis. In all lesions E6, E7, and L1 gene fragments of canine oral papillomavirus (COPV) DNA were detected by PCR and sequencing analysis. ISH revealed COPV DNA in a highly specific pattern within nuclei of the hyperplastic epithelium. The presence of canine papillomavirus in ocular conjunctival plaques and papillomas suggests these benign lesions may have the potential for malignant transformation. This is the first time that the lambdapapillomavirus COPV has been detected in ocular epithelial hyperplastic lesions.

Prognostic factors and survival analysis in a sample of oral squamous cell carcinoma patients

The aims of this report were to describe the 5-year overall survival (OS) in a group of oral squamous cell carcinoma (OSCC) patients and to investigate the effects of age, gender, anatomic localization, tumor evolution time, smoking and alcohol intake, nodal status, tumoral recurrences, histologic classification, p53 and p63 immunoexpression, human papillomavirus DNA presence, and treatment on the prognostic outcome. Survival curves were generated using Kaplan-Meier method, and univariate and multivariate analyses were made using the log rank test and Cox regression, respectively. The 5-year OS was 28.6%, and the univariate analysis showed significant results for p53 and p63 immunoexpression, age, and anatomic localization. The Cox regression demonstrated poor OS for tumors with p53 immunoexpression and for patients aged over 60 years. There were also significant differences in survival depending on the anatomic localizations. These results highlight the influence of p53 immunoexpression, age, and anatomic localization in OSCC evolution.

Prevalence and genotyping of human papillomavirus infection in women with vulvodynia

Evidence of vulvar human papillomavirus infection varies and the frequency of the different genotypes has not been adequately assessed. Fifty consecutive sexually active healthy patients with vulvodynia and suspected of human papillomavirus infection underwent a vulvoscopy and biopsy. Ten normal vulvar samples were also enrolled as control. Histological and vulvoscopic findings were compared in relation to human papillomavirus-DNA presence and genotyping by a broad-spectrum polymerase chain reaction and reverse hybridization line probe assay. Although the clinical and histological diagnoses did not always coincide, a good association was found (p<0.0001). Human papillomavirus-DNA was detected in 42% of all biopsies and in none of the controls, and less frequently in acetowhite-positive patients (33.3%, p<0.03). Squamous papillomatosis (74%) was the most frequent histological diagnosis, followed by condyloma (20%). Condyloma (90%) but not squamous papillomatosis (29.7%) was significantly associated with human papillomavirus-DNA presence. Out of the vulvoscopically normal patients, one (33%) was human papillomavirus-DNA positive. Out of the recorded microscopic features, only koilocytosis was associated with human papillomavirus-DNA presence. Eight different human papillomavirus genotypes were detected: high-risk 16 (43%), 31 (19%), 52 (14.3%), 68, and 59 (4.8% each), and low-risk types 6 (71.4%), 11, and 40 (4.8% each); 33.3% of infections were multiple, ranging from 2 to 4 genotypes. Out of the human papillomavirus-DNA positive squamous papillomatosis, 72.7% showed a high-risk type but the infection remained episomal. Our data confirm human papillomavirus as a frequent cause of vulvodynia and its frequent association with squamous papillomatosis or condyloma. The high-risk human papillomavirus in squamous papillomatosis suggests screening for possible undiagnosed cervical infection.

Papillomavirus in healthy skin of Australian animals

Papillomaviruses are a group of ubiquitous viruses that are often found in normal skin of humans, as well as a range of different vertebrates. In this study, swab samples collected from the healthy skin of 225 Australian animals from 54 species were analysed for the presence of papillomavirus DNA with the general skin papillomavirus primer pair FAP59/FAP64. A total of five putative and potential new animal papillomavirus types were identified from three different animal species. The papillomaviruses were detected in one monotreme and two marsupial species: three from koalas, and one each from an Eastern grey kangaroo and an echidna. The papillomavirus prevalence in the three species was 14 % (10/72) in koalas, 20 % (1/5) in echidnas and 4 % (1/23) in Eastern grey kangaroos. Phylogenetic analysis was performed on the putative koala papillomavirus type that could be cloned and it appears in the phylogenetic tree as a novel putative papillomavirus genus. The data extend the range of species infected by papillomaviruses to the most primitive mammals: the monotremes and the marsupials.

Prognostic significance of high-risk HPV status in advanced cervical cancers and pelvic lymph nodes

Objective. In this study, we investigated the presence of high-risk (HR) HPV types most prevalent in the Hungarian population in surgically removed cervical cancers and pelvic lymph nodes. The aim of our work was to determine the prognostic significance of HPV status in the lymph nodes draining the tumor. Methods. Primary tumor specimens from 150 patients and 900 lymph node samples (six per case) were studied. Fifty-six/150 were early (FIGO IA-IB) stage, while 94/150 were advanced (FIGO IIA-IIIB) stage cancers. Beside histopathological evaluation, DNA extracted from the tissue samples was subjected to nested PCR to detect characteristic type-specific sequences of HPVs 16, 18 and 33. Moreover, clinicopathological data were collected for an average 48-month postoperative follow-up period for the purposes of statistical analysis. Results. The presence of HR-HPV types in the lymph nodes shows no correlation with disease-free survival, whereas the presence of lymph node metastases significantly decreases life expectancy ( P = 0.002). Lymph nodes with metastases more frequently carry HR-HPV than nodes with no evidence of tumorous infiltration (65% versus 36%, P < 0.001); however, a high number of metastases surrounding HR-HPV-positive tumors were found negative for the viruses (42/120). Conclusions. HR-HPV status of pelvic lymph nodes draining cervical cancers has no noticeable influence on the life expectancy of the patients. HR-HPV-positive tumor cells do not necessarily have a selective advantage in forming metastases. Presumably, a number of alterations in cellular genes rather than the presence of papillomavirus DNA may have a decisive role in the progression of cervical cancers.

Antibodies against human papillomavirus (HPV) type 16 and 18 E2, E6 and E7 proteins in sera: Correlation with presence of papillomavirus DNA

Human papillomavirus (HPV) infection is associated with cervical cancer. The E2 and E1 papillomavirus proteins are expressed at the early stage of infection and regulate DNA replication. The E2 protein activates and represses transcription from different HPVs promoters. At some stage when viral DNA gets integrated into the cellular genome, the E2 gene is disrupted or inactivated. This event leads to a derepression of the E6 and E7 viral oncogenes. These viral proteins are required normally for the maintenance of the malignant phenotype. Therefore, the E2, E6, and E7 proteins are present in all patients infected by papillomavirus. In this study, the association of antibody levels against E2, E6, and E7 proteins of HPV types 16, 18, and 6 was determined in relation to the presence of HPV DNA at the initial stages of HPV infection. Serum samples from 172 women with HPV infection, determined by Papanicolau (Pap) smears and colposcopy, were tested. Elevated antibody titers against E2 protein from the HPV 6 and HPV 16 were detected in 46.42 and 66.96% of the patients, respectively. Antibodies against the E7 and E6 proteins of HPV 16 were found in 51.78 and 36.60% of the patients, respectively. Antibodies against the E6 and E7 proteins of HPV 18 were 35 and 45%, respectively. A statistical difference was found for antibody titers against the E2, E6, and E7 proteins between patients with papillomavirus DNA and controls cases who had no cytological abnormalities and no HPV DNA. Sera titers were 1/500 for patients HPV positive and 1/50 for control individuals. Antibodies titers against E6 and E7 proteins were also examined in patients at 6 and 24 months after cryosurgery. In these patients, a slight decrease in the antibody level against the E2, E6, and E7 proteins was found. No correlation was found between age and number of sexual partners, with serum positivity to the E2, E6, and E7 papillomavirus proteins. These data suggest that antibodies against the E2, E6, and E7 proteins are good candidates for use as markers for monitoring cervical HPV infections.

Age-dependence of human papillomavirus DNA presence in oral squamous cell carcinomas.

The aetiology of oral cancer is thought to be multifactorial. Apart from the two known major risk factors (tobacco and alcohol), a viral aetiology has been proposed, with special reference to human papillomavirus (HPV). 35 cases of oral squamous cell carcinoma (OSCC), seen at the Departments of Oral & Maxillofacial Surgery and Oral Pathology and Otolaryngology of the Free University of Amsterdam, were analysed as well as 12 biopsies of clinically and histologically normal gingival mucosa collected from healthy individuals after tooth extractions, using the polymerase chain reaction (PCR) and two different sets of primers that are able to detect a broad spectrum of HPV types. An overall HPV positivity of 54.3% in OSCC was found, the majority of positive cases (78.9%) harbouring HPV type 16. In contrast, no positivity for HPV was detected in the clinically normal oral mucosal samples analysed. Furthermore, a significant association between HPV presence and age was found: patients older than 60 years showed a lower prevalence of the virus (29.4%) compared with patients below this age (77.8%) (P < 0.05). The results from the present study suggest an association between HPV and OSCC, particularly in patients under the seventh decade.

Use of the Dot-Blot technique in the detection of human papillomavirus(HPV) deoxyribonucleic acid (DNA) in malignant tumors of the oropharynx

A total of 23 malignant oropharyngeal tumours (palate, tongue, tonsils, pharynx) and two lymph node metastases were analysed for presence of papilloma virus DNA. Thirteen (54.5%) of 22 squamous cell cancers of different koilocytosis and grading were found to contain HPV 16/18 DNA. Only 16.6% (4 cases) were positive for HPV 6/11 DNA. There was no detectable HPV-DNA in the lymph node metastases (Table 1). The control biopsies (19) were negative after hybridisation.

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: A clinical and molecular biological study

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis sufferers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at > 35 years developing tumours about four times more rapidly than patients ≤ 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.

Cloning and molecular characterization of an oral papillomavirus of domestic rabbits

DNA obtained from New Zealand white rabbit oral papillomas was analyzed for the presence of papillomavirus DNA. The viral genome was cloned as three separate subdones, which were each mapped and oriented with respect to one another. Comparisons with other papillomavirus DNAs by Southern blot hybridization under various conditions of stringency revealed a strong area of conservation among the DNAs of the rabbit oral papillomavirus (ROPV) and CRPV, HPV-1a, HPV-16, and BPV-5, but not with 12 other papillomavirus DNAs. This region, which spans the junction of the presumptive E2 and L2 open reading frames of ROPV, was sequenced and compared to other known papillomavirus sequences. These analyses revealed a high degree of DNA homology in the C-terminal E2 and N-terminal L2 regions between ROPY and both HPV-1 a and CRPV. The homology with HPV-16 was limited to the L2 open reading frame. The predicted amino acid sequences of each region were also compared and bore out the same conclusions. In addition, no E5 open reading frame was detected in the ROPY sequence.

Papillomviren in benignen und malignen Tumoren des Mundes und des oberen Respirationstraktes*

A total of 113 benign and malignant tumours of the mouth and upper respiratory tract have been analysed for the presence of papilloma virus DNA. Thirty-four (63%) of 54 papillomatous lesions were found to contain such DNA. Seventy-two percent of the laryngeal papillomas contained HPV 6 or HPV 11 DNA, whereas the oral papillomatoses harboured HPV 6 (15.6%), HPV 11 (9.4%), HPV 7 (9.4%), HPV 13 (12.5%) and HPV 32 (9.4%) DNAs. The high number of HPV 7 DNA-positive lesions was unexpected. In most of the malignant tumours no papilloma-viral DNA was found, with the exception of 3 tongue-base carcinomas, and in a metastasis from one of the tumours, which contained HPV 16 (3 biopsies) and HPV 2 related sequences (1 biopsy).

Human papillomavirus DNA in conjunctival papilloma.

A histologically proven conjunctival papilloma was examined for the presence of papillomavirus DNA by nucleic acid hybridization under relaxed conditions. It harbored papilloma-virus-specific DNA, which showed no detectable relationship with that of known virus types when tested under stringent conditions. This demonstrates that conjunctival papillomas are associated with more than one papillomavirus type. Viral diagnosis may turn out to be of prognostic value.