Identification Of Papillomavirus Research Articles

Genomic Profiles and Clinical Outcomes of Penile Squamous Cell Carcinoma With Elevated Tumor Mutational Burden.

Tumor mutational burden (TMB) is a putative biomarker of efficacy for immune checkpoint inhibitor (ICI) therapies of solid tumors, but not specifically for penile squamous cell carcinoma (PSCC). To characterize biomarker features and ICI therapy outcomes associated with high TMB in PSCC in the routine clinical practice setting. In this cohort study, 397 PSCC cases were analyzed to identify genomic alterations in more than 300 cancer-associated genes and genomic signatures, including TMB, using a hybrid capture-based comprehensive genomic profiling assay. Tumor mutational burden was categorized as low (<10 mutations per megabase [mut/Mb]), high (10-19 mut/Mb), or very high (≥20 mut/Mb). Germline status of genetic alterations was predicted using a validated somatic-germline computational method. Clinical outcomes of patients with metastatic PSCC receiving first-line ICI were abstracted using the deidentified nationwide Clinico-Genomic Database (CGDB) from January 1, 2011, through December 31, 2022. Comprehensive genomic profiling was performed using FoundationOne and FoundationOne CDx assays from Foundation Medicine Inc. The spectrum of genetic alterations by TMB level in PSCC, the percentage of germline genetic alterations, and the outcome (overall survival with routine clinical treatment) by TMB of chemotherapy-naive patients with PSCC who received ICI treatment up front were assessed in this descriptive study. Among 397 patients (median [IQR] age, 65 [54-73] years; 266 [67.0%] of European, 83 [20.9%] of admixed American, and 34 [8.5%] of African or other genomic ancestry), the median (IQR) age (eg, 65 [53-73] years for low TMB vs 68 [61-78] years for TMB ≥10 mut/Mb) and genomic ancestry distribution (eg, European 228 of 339 [67.3%] for low TMB vs 38 of 58 [65.5%] for TMB ≥10 mut/Mb) were similar between TMB subgroups. There were 339 PSCC cases (85.4%) with low TMB, 40 cases (10.1%) with high TMB, and 18 cases (4.5%) with very high TMB. Comparisons of TMB of 10 mut/Mb or higher vs low TMB showed an enrichment of genetic alterations in PIK3CA (48.3% vs 18.3%; P < .001) and KMT2D (29.3% vs 7.7%; P < .001) and less frequent genetic alterations in CDKN2A (25.9% vs 45.7%; P = .05). Most genetic alterations did not co-occur. Human papillomavirus identification was more frequent as TMB increased: 28.3% for low TMB, 50.0% for high, and 72.2% for very high. In total, 95 of 1377 genetic alterations (6.9%) were germline. Of 10 patients identified from the CGDB receiving frontline ICIs, median (IQR) follow-up was 9.9 months. Four patients had overall survival with clinical treatment of more than 12 months, including 2 of 3 patients with TMB of 10 mut/Mb or higher. In this cohort study of advanced metastatic PSCC based on TMB levels, significant differences were observed for biomarkers in nearly 15% of patients with a TMB of 10 mut/Mb or higher. Germline testing and ICI-based therapy should be integrated into the management of selected PSCC cases.

Virus papiloma humano y factores asociados en pacientes con citología desconocida atendidas en el norte de Perú

Introducción. El virus papiloma humano es el causante del cáncer de cuello uterino, uno de los cánceres más comunes en las mujeres. Objetivo. Determinar la prevalencia del virus papiloma humano y los factores asociados en mujeres con citología desconocida. Métodos. En pacientes de ginecoobstetricia con citología desconocida atendidas en el Hospital Regional Lambayeque, en la costa norte del Perú, entre abril y junio 2019, se realizó la extracción de ADN para identificar el virus del papiloma humano basada en el método de salting out. Se procesaron las muestras mediante reacción en cadena de la polimerasa y se amplificaron para los primers MY09 y MY11, y PC04/GH20. Se empleó el análisis bivariado mediante la prueba de chi cuadrado y t-student. Resultados. Se encontró que 29,9% de las pacientes atendidas en el área de gineco-obstetricia con citología desconocida tuvieron el virus del papiloma humano. No se encontró diferencia estadística significativa entre la infección por virus del papiloma humano con la edad, edad de primera relación sexual, promiscuidad, número de partos vaginales, lesión de cuello uterino, antecedente de ITS, uso de anticonceptivo hormonal, uso del condón y tabaquismo.

High-Risk Human Papillomavirus Identification in Precancerous Cervical Intraepithelial Lesions.

This review aims to summarize the currently available human papillomavirus (HPV) testing methods for precancerous cervical intraepithelial lesions. A literature search of PubMed using key words "high-risk HPV, precancerous cervical intraepithelial lesions, FDA-approved HPV tests, p16 IHC, Ki 67 IHC, fluorescent in situ hybridization for HPV, Pap smear, HPV vaccines, HPV tests using self-collected samples, and next-generation sequencing" was performed between January 1 and June 14, 2019. The package inserts of the Food and Drug Administration-approved HPV tests were obtained from the companies' Web sites. Multiple morphology-based, immunohistochemical staining and nucleic acid HPV tests were reviewed, including the material required, methodologies, result interpretations, as well as their advantages, limitations, and futures. The structure of HPV and its natural history of infection and transmission were touched on as well for a better understanding of these testing methods. Human papillomavirus tests are a critical component for cervical cancer screening, and understanding of these tests helps test results interpretation and patients' triage.

Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test: A strobe-compliant article.

The aim of this study was to identify the association between human papilloma virus (HPV) infection and ocular surface squamous neoplasia (OSSN) using p16 immunohistochemistry (IHC) and deoxyribonucleic acid (DNA) chip test.Thirty-eight patients who underwent surgical excision of OSSN were retrospectively studied using tissue samples. The IHC was performed to assess the expression of p16 and DNA chip test was used to detect 24 HPV serotypes.Among the 38 OSSN samples, 32 cases (84.2%) were histopathologically categorized as pre-invasive type and 6 cases (15.8%) as invasive type. The IHC for p16 showed strong positivity in 12 cases (31.6%), whereas it was negative in 26 cases (68.4%). On the other hand, only one case (2.6%) of invasive OSSN was positive for the HPV16 serotype, as assessed by DNA chip test.In OSSN, p16 expression was positive in approximately 1/3rd of the cases, whereas the majority of the 24 HPV serotypes were negative for p16. Our findings suggest that only a weak association exists between HPV infection and OSSN.

Molecular identification of papillomavirus in ducks

Papillomaviruses infect many vertebrates, including birds. Persistent infections by some strains can cause malignant proliferation of cells (i.e. cancer), though more typically infections cause benign tumours, or may be completely subclinical. Sometimes extensive, persistent tumours are recorded–notably in chaffinches and humans. In 2016, a novel papillomavirus genotype was characterized from a duck faecal microbiome, in Bhopal, India; the sixth papillomavirus genotype from birds. Prompted by this finding, we screened 160 cloacal swabs and 968 faecal samples collected from 299 ducks sampled at Ottenby Bird Observatory, Sweden in 2015, using a newly designed real-time PCR. Twenty one samples (1.9%) from six individuals (2%) were positive. Eighteen sequences were identical to the published genotype, duck papillomavirus 1. One additional novel genotype was recovered from three samples. Both genotypes were recovered from a wild strain domestic mallard that was infected for more than 60 days with each genotype. All positive individuals were adult (P = 0.004). Significantly more positive samples were detected from swabs than faecal samples (P < 0.0001). Sample type data suggests transmission may be via direct contact, and only infrequently, via the oral-faecal route. Infection in only adult birds supports the hypothesis that this virus is sexually transmitted, though more work is required to verify this.

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins.

The family Papillomaviridae contains more than 320 papillomavirus types, with most having been identified as infecting skin and mucosal epithelium in mammalian hosts. To date, only nine non-mammalian papillomaviruses have been described from birds (n = 5), a fish (n = 1), a snake (n = 1), and turtles (n = 2). The identification of papillomaviruses in sauropsids and a sparid fish suggests that early ancestors of papillomaviruses were already infecting the earliest Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living vertebrate species, and progeny virus could have been passed on to all members of this clade, inhabiting virtually every habitat on the planet. As part of this study, we isolated a novel papillomavirus from a 16-year-old female Adélie penguin (Pygoscelis adeliae) from Cape Crozier, Ross Island (Antarctica). The new papillomavirus shares ∼64 per cent genome-wide identity to a previously described Adélie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian viruses (expect the python, Morelia spilota, associated papillomavirus) cluster near the base of the papillomavirus evolutionary tree. A papillomavirus isolated from an avian host (Northern fulmar; Fulmarus glacialis), like the two turtle papillomaviruses, lacks a putative E9 protein that is found in all other avian papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more similar to the mammalian viruses than the other avian papillomaviruses. Typical E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas the sauropsid papillomaviruses only have one such motif. Furthermore, this motif is absent in the fish papillomavirus. Thus, it is highly likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6. It appears that a motif duplication resulted in mammalian papillomaviruses having a double Zinc finger motif in E6. We estimated the divergence time between Northern fulmar-associated papillomavirus and the other Sauropsid papillomaviruses be to around 250 million years ago, during the Paleozoic-Mesozoic transition and our analysis dates the root of the papillomavirus tree between 400 and 600 million years ago. Our analysis shows evidence for niche adaptation and that these non-mammalian viruses have highly divergent E6 and E7 proteins, providing insights into the evolution of the early viral (onco-)proteins.

Human Papilloma Virus Identification in Breast Cancer Patients with Previous Cervical Neoplasia.

Women with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active. A range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. The same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001). These findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

High-throughput and automatic typing via human papillomavirus identification map for cervical cancer screening and prognosis

A novel human papillomavirus (HPV) typing assay for cervical cancer screening and prognosis was developed by the combination of restriction fragment length polymorphism (RFLP) and microchip electrophoresis (MCE) to achieve higher levels of sensitivity and throughput. The detection limit of 2 × 10(2) copies, high sensitivity and typing accuracy on the account of PCR-RFLP-MCE method guarantee the successful diagnosis results of 4-fold higher infection rate over cytologic tests. From clinical samples, eleven kinds of HPV types were identified with a good compatibility degree of over 90%. The described method showed good reliability in clinical samples and provided a promising alternative for pathological studies at the molecular level.

Assessment of the efficacy of a new formulation for plantar wart mummification: new experimental design and human papillomavirus identification

Cutaneous warts are caused by infection of the epidermis with human papillomavirus (HPV). Cryotherapy using liquid nitrogen is one of the most common local treatments. In this study, we used a novel ex vivo approach to compare the efficacy of a new product with conventional liquid-nitrogen cryotherapy by studying epidermal histology and assessing the presence of HPV types 1 and 2 DNA in plantar warts. The studied formulation, which acts by tissues mummification, is a combination of nitric acid, organic acids and metallic salts. We found that, similar to liquid nitrogen, the studied product induced alterations in the wart structure. In addition, unlike liquid nitrogen, this product also reduced the amount of HPV DNA. The results suggest that there is a poor correlation between the histological response and the antiviral efficacy of standard wart treatment.

Sensitivity and specificity of the human papillomavirus identification test

When the sensitivity of a test such as the Pap smear is determined, both positive and negative results should be submitted to the gold standard of histology. If this is not done, the sensitivity will be unrealistically high. The human papillomavirus (HPV) test has not been adequately investigated in this way. In this letter I report a preliminary study in which the HPV test was evaluated against histology in all cases.

Molecular Identification of Bovine Papillomaviruses Associated with Cutaneous Warts in Southern Brazil

Bovine papillomaviruses (BPVs) are widespread pathogens mainly associated with benign, self-limiting, cutaneous lesions (warts). At least 8 viral types, defined by serology or nucleotide sequences of the L1 gene, have been identified to date. Different serotypes are associated with the specific type and morphology of the lesion and with particular geographical regions. This article describes the molecular identification of papillomaviruses from Brazilian cattle (n = 48) and horses (n = 1) through partial amplification and sequencing of the L1 gene. Bovine papillomavirus-1 (BPV-1) was identified in warts from 29 cattle (59%), BPV-6 from 9 cattle (18%), and BPV-2 in 8 lesions (16%). Warts of 2 cattle harbored L1 sequences of a new BPV type (BAA5), otherwise identified almost exclusively in healthy skin. The newly proposed BPV type "BR-UEL-4" was identified in a sarcoid tumor of a horse. Thus, the present report provides information on the main types of BPV involved in bovine papillomatosis in Brazil and reveals a new viral type associated with equine sarcoid, which to date has been attributed exclusively to BPV-1 and BPV-2.

Human papillomavirus expression and p53 gene mutations in squamous cell carcinoma.

To determine the incidence of human papillomavirus (HPV) infection and p53 gene mutation expression in squamous cell carcinomas (SCCs) of the oral cavity and tonsils, to correlate the presence of HPV and p53 gene mutation with known clinical and pathological features of SCC, and to determine whether infection with HPV or the presence of p53 gene mutations are independent prognosticators of patient survival. To accomplish this goal, 58 patients with SCCs of the oral cavity and 42 patients with SCCs of the tonsils were randomly examined. The cases examined met the criteria of 5-year clinical follow-up, availability of complete staging information and treatment history, and the presence of paraffin-embedded tumor specimens. Immunohistochemical tests were performed to identify the mutant p53 protein. Human papillomavirus identification was accomplished with polymerase chain reaction, with confirmation via restriction fragment length polymorphisms. The incidence of p53 gene mutation expression for this series was 66%. Human papillomavirus infection was found in 11 patients (11%). There was a trend toward increased p53 gene mutation expression with advancing stage of tumor in the oral cavity cancer group, although this was less evident in the tonsil cancer population. The p53 gene mutation status was found not to correlate with the histological grade of the tumor, patient age or sex, recurrence rates, or survival status. Like p53 expression, there were no correlations found between the presence of HPV and age, sex, histological grade, or recurrence rates. However, a correlation did exist between HPV and survival status in the tonsil cancer group, with improved survival noted among patients with tonsil cancers infected with HPV compared with those not infected with HPV. A significant correlation existed with both p53 gene mutation status and HPV status with respect to alcohol and tobacco use. The presence of the p53 gene mutation positively correlated with increased tobacco and alcohol use, whereas infection with HPV predicted a significantly lower rate of alcohol and tobacco consumption. Human papillomavirus infection is an independent risk factor for the development of oral cavity and tonsil SCCs in those patients with a relatively low alcohol and tobacco use history. Conversely, there is a strong association between heavy alcohol and tobacco use and mutation of the p53 gene. Neither p53 gene mutation nor HPV infection serve as prognosticators of tumor behavior in SCCs of the oral cavity or tonsils, with the exception of improved survival noted among patients with tonsil cancers infected with HPV.

Identification of papillomaviruses in scrapings from bovine warts by use of the polymerase chain reaction.

Bloch, N., Sutton, R.H., Breen, M. and Spradbrow, P.B., 1997. Identification of papillomaviruses in scrapings from bovine warts by use of the polymerase chain reaction. Veterinary Research Communications, 21 (1), 63-68.

Human Papillomavirus Identification and Typing of Both Sexual Partners

To investigate the efficacy of diagnostic methods for human papillomavirus (HPV) infection. The diagnostic methods were morphologic and immunohistochemical techniques and in situ hybridization. The first ones consisted of (1) a cytologic smear on the females, (2) cytologic examination of a urethral brushing on the males, (3) colposcopy on the females, and (4) histologic examination of the uterine cervix. A synchronous HPV infection was found in 50% of the sexual partners. HPV was detected also in 30% of cervical biopsies by immunohistochemistry. In situ hybridization was performed on both the cervical biopsies and urethral samples from the males. By this method the same subtype of the virus was observed in both sexes. The types of HPV were identified in 45% of 20 females and 80% of 20 males. Analytically, in men, 7 cases of HPV 6/11 types, 3 cases of 16/18, 5 cases of 31/33/35 and 1 case each of 16/18 and 31/33/35 were observed. In women, in 4 cases subtypes 6/11, in 2 cases types 16/18 and in 3 cases types 31/33/35 were identified. Male partners of women with HPV infection should be investigated in order to produce greater insight into HPV prevalence and the mechanisms of viral transmission.

Comparison of ViraPap, Southern hybridization, and polymerase chain reaction methods for human papillomavirus identification in an epidemiological investigation of cervical cancer.

In order to provide a reliable diagnosis for the presence and type of human papillomavirus (HPV) DNA in a case-control study of cervical cancer in Colombia and Spain, 926 cervical scrapes from female subjects were examined by ViraPap (VP) and Southern hybridization (SH), and 510 of these (263 cases and 247 controls) were also tested by polymerase chain reaction (PCR) using the HPV L1 consensus primers. HPV DNA prevalence was much higher in cases than in controls by each of the three tests. There was complete agreement between the results of the three tests for 64.9% of the 510 specimens; 53.5% were negative and 11.4% were positive (regardless of type) by all tests. An additional 29.0% of the specimens were positive by PCR: 19.4% by PCR alone, 6.7% by PCR and VP, and 2.9% by PCR and SH. SH and/or VP gave positive results for 6.0% of the specimens for which the PCR finding was negative: 2.7% by SH alone, 2.5% by VP alone, and 0.8% by both VP and SH. When specimens which were positive by VP alone or only by SH at low-stringency conditions were excluded, PCR confirmed all but four specimens which were positive by other tests. The concordance between type-specific diagnosis by SH and PCR was 86% when HPVs were typed in both tests. HPV-16 accounted for over 80% of the typed HPVs in each test. The presence of blood in case specimens did not appear to inhibit HPV positivity by VP or by PCR at the dilution tested. Low amounts of cellular DNA of specimens resulted in some underestimation of HPV positivity by VP and SH but not by PCR. Compared with that of PCR, the sensitivities for case specimens were 38% by SH and 50% by VP; the sensitivity for control specimens, although it could not be measured precisely because there were few positive specimens, appeared to be lower than for case specimens. It was concluded that PCR-based tests are best suited for epidemiological investigation of HPVs.

The L2 open reading frame of human papillomavirus type 1a encodes a minor structural protein carrying type-specific antigens

The proteins encoded by the open reading frames of papillomavirus genomes and the minor polypeptides detected in purified virions are still poorly defined. We show here by its expression in Escherichia coli that the open reading frame L2 of human papillomavirus type 1a codes for a minor structural protein of Mr 76,000. Antisera raised against a truncated L2-beta-galactosidase fusion protein in which the conserved N-terminal region of L2 is missing are type specific for human papillomavirus type 1 virions and are reactive at high dilutions. Expression of the L2-encoded type-specific antigens thus provides a powerful new tool for the identification of papillomaviruses.

Identification of Papillomaviruses in Butchers' Warts

We have studied the papillomaviruses found in the hand warts of 60 butchers, most of them from 2 distant slaughterhouses. Warts differing in morphology and location were studied separately. The viruses were identified by molecular hybridization, restriction enzyme analysis and immunofluorescence. Four known human papillomaviruses (HPV-1, HPV-2, HPV-3, HPV-4) were detected and one hitherto unknown papillomavirus was identified in 9 butchers. The DNA of the latter virus did not anneal with any of the RNAs complementary to either HPV-1 to HPV-5 or bovine papillomavirus type 1 (BPV-1) DNAs, and showed a Hind II + III restriction enzyme cleavage pattern distinct from those of known HPVs and BPVs. This virus showed distinct antigenic properties, as shown by immunofluorescence, using HPV-1, -2, -3, -5, and BPV-1 antisera. It may represent a new type of human papillomavirus (HPV-7) or a yet unidentified animal papillomavirus. In addition, 6 butchers were found to be infected with a papillomavirus, distinct from the known skin HPVs and from BPV-1, which could not be characterized by restriction enzyme analysis. Eleven butchers were found to be infected by 2 viruses. A characteristic histological pattern was found to be associated with the different papillomaviruses.