Table 1 - uploaded by Irene M Leigh
Content may be subject to copyright.
Source publication
A total of 118 biopsies from skin lesions of 46 renal allograft patients was analyzed for human papillomavirus (HPV) DNA by polymerase chain reaction with degenerate primers and also partially by subsequent se quencing of the amplified fragment. Sixty-two % of the benign prolifer ations (31 of 50) contained DNA of known HPV types as well as HPV seq...
Similar publications
Unlabelled:
Verruca vulgaris (common warts) is a benign lesion of skin and mucous membranes caused by human papillomavirus (HPV). The lesions are typically self-limited but may vary in size and number. The occurrence on the tongue is extremely rare. To the best of our knowledge, only one verruca vulgaris existing in the tongue had been reported in...
Citations
... The close association of viral gene expression with at least some actinic keratoses is consistent with an early causal role for BetaPV in the development of such lesions in OTR. It is apparent, however, that not all studies have observed marked differences in DNA copy number between normal skin/benign lesions and (pre-)cancerous skin [117,118], which leads us to suspect that actinic keratoses may in fact be a heterogeneous group with regard to BetaPV copy number and gene expression patterns. Occasionally, an association between BetaPV infection and BCC has been observed, and in particular this is noticeable when HPV20 serological responses and BCC are compared119120121. ...
Although the role of oncogenic Alpha human papillomaviruses (HPV) in the development of mucosal carcinomas at different body sites (e.g., cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KC, basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC.
... Chen et al, unpublished data). A BLAST search against GenBank revealed that most types have been previously reported as partial FAP sequences obtained from skin lesions and samples [12,161718192021. Novel types accounted for 28 infections in the oral samples. ...
Human papillomaviruses (HPVs) primarily sort into 3 genera: Alphapapillomavirus (α-HPV), predominantly isolated from mucosa, and Betapapillomavirus (β-HPV) and Gammapapillomavirus (γ-HPV), predominantly isolated from skin. HPV types might infect body sites that are different from those from which they were originally isolated.
We investigated the spectrum of HPV type distribution in oral rinse samples from 2 populations: 52 human immunodeficiency virus (HIV)-positive men and women and 317 men who provided a sample for genomic DNA for a prostate cancer study. HPV types were detected with the MY09/MY11 and FAP59/64 primer systems and identified by dot blot hybridization and/or direct sequencing.
Oral rinse specimens from 35 (67%) of 52 HIV-positive individuals and 117 (37%) of 317 older male participants tested positive for HPV DNA. We found 117 type-specific HPV infections from the HIV-positive individuals, including 73 α-HPV, 33 β-HPV, and 11 γ-HPV infections; whereas, the distribution was 46 α-HPV, 108 β-HPV, and 14 γ-HPV infections from 168 type-specific infections from the 317 male participants.
The oral cavity contains a wide spectrum of HPV types predominantly from the β-HPV and γ-HPV genera, which were previously considered to be cutaneous types. These results could have significant implications for understanding the biology of HPV and the epidemiological associations of HPV with oral and skin neoplasia.
... In hosts with primary immuno-deficiency or with a genetic predisposition, cutaneous HPVs -especially Betapapilloma-viruses -can cause serious clinical manifestations, such as numerous benign and malignant tumors in patients with the hereditary disease epidermodysplasia verruciformis [9]. In immuno-suppressed patients, such as renal transplant recipients, infection with cutaneous HPVs can similarly lead to the development of various benign and malignant skin tumors1011121314. Additionally, several Betapapillomavirus HPVs, such as HPV-22, HPV-38, HPV-92 or HPV-96, have been etiologically linked with the development of squamous cell carcinoma of the skin15161718. ...
DNA from two novel HPV genotypes, HPV-150 and HPV-151, isolated from hair follicles of immuno-competent individuals, was fully cloned, sequenced and characterized. The complete genomes of HPV-150 and HPV-151 are 7,436-bp and 7,386-bp in length, respectively. Both contain genes for at least six proteins, namely E6, E7, E1, E2, L2, L1, as well as a non-coding upstream regulatory region located between the L1 and E6 genes: spanning 416-bp in HPV-150 (genomic positions 7,371 to 350) and 322-bp in HPV-151 (genomic positions 7,213 to 148). HPV-150 and HPV-151 are phylogenetically placed within the Betapapillomavirus genus and are most closely related to HPV-96 and HPV-22, respectively. As in other members of this genus, the intergenic E2-L2 region is very short and does not encode for an E5 gene. Both genotypes contain typical zinc binding domains in their E6 and E7 proteins, but HPV-151 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of the novel genotypes, quantitative type-specific real-time PCR assays were developed. The 95% detection limits of the HPV-150 and HPV-151 assays were 7.3 copies/reaction (range 5.6 to 11.4) and 3.4 copies/reaction (range 2.5 to 6.0), respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (total of 540 samples) revealed that HPV-150 and HPV-151 are relatively rare genotypes with a cutaneous tropism. Both genotypes were found in sporadic cases of common warts and SCC and BCC of the skin as single or multiple infections usually with low viral loads. HPV-150 can establish persistent infection of hair follicles in immuno-competent individuals. A partial L1 sequence of a putative novel HPV genotype, related to HPV-150, was identified in a squamous cell carcinoma of the skin obtained from a 64-year old immuno- compromised male patient.
... Members of Alphapapillomavirus species 2 were first found in patients with the hereditary disorder epidermodysplasia verruciformis [8] and are most frequently associated with flat or plane and intermediate skin warts in immunocompetent individuals91011. In immuno-suppressed patients, such as solid-organ recipients, these genotypes are also associated or can co-localize with dysplastic warts and non-melanoma skin cancer12131415. In this study, a novel HPV genotype, isolated originally from a hand wart (isolate SIBX9) and initially characterized by our group in 2004 [16], was characterized fully and deposited in the Reference Centre for Papillomaviruses in Heidelberg, Germany, where it was assigned its official name, HPV-125. In addition, a quantitative type-specific real-time PCR (RT-PCR) was developed and a representative collection of HPV-associated benign and malignant neoplasms and hair follicles was tested in order to assess the tissue predilection and clinical significance of HPV-125. ...
... The initial 474-bp sequence of the HPV-125 L1 gene (GenBank Acc. No: AJ810860, corresponding to nucleotide positions 5,994–6,468 of the HPV-125 complete genome) was obtained by the use of primers HVP2 (59-TCNMGNGGNCANCCNYTNGG-39 [14]) and B5 (59-AYNCCRTTRTTRTGNCCYTG -39 [13]) and FastStart Taq DNA polymerase kit (Roche Applied Science) on a PE9700 Thermo Cycler (Applied Biosystems, Foster City, CA). PCR was carried out in a 25 ml reaction volume containing 5 ml (100 ng) of extracted DNA, 2.5 ml of 106 PCR Reaction Buffer, 200 mM (each) of dATP, dCTP, dGTP, and dTTP, 1.5 mM of MgCl 2 , 1.25 U of FastStart Taq DNA Polymerase, and 25 pmol of each primer. ...
... HPV-125 was detected in 2004 in the biopsy specimen of a hand wart obtained from a 19 year-old immuno-competent male patient at the Department of Dermatovenereology, University Medical Centre, Ljubljana, Slovenia. It was initially identified as a putative novel HPV genotype by the use of HVP2/B5 primers [13,14], designed to detect various cutaneous HPVs, with which a 474-bp sequence of the L1 gene was amplified and sequenced. This partial L1 sequence was deposited in GenBank as strain SIBX9 (Acc. ...
The DNA genome of a novel HPV genotype, HPV-125, isolated from a hand wart of an immuno-competent 19-year old male was fully cloned, sequenced and characterized. The full genome of HPV-125 is 7,809-bp in length with a GC content of 46.4%. By comparing the nucleotide sequence of the complete L1 gene, HPV-125 is phylogenetically placed within cutaneotrophic species 2 of Alphapapillomaviruses, and is most closely related to HPV-3 and HPV-28. HPV-125 has a typical genomic organization of Alphapapillomaviruses and contains genes coding for five early proteins, E6, E7, E1, E2 and E4 and two late capsid proteins, L1 and L2. The genome contains two non-coding regions: the first located between the L1 and E6 genes (nucleotide positions 7,137-7,809, length 673-bp) and the second between genes E2 and L2 (nucleotide positions 3,757-4,216, length 460-bp). The E6 protein of HPV-125 contains two regular zinc-binding domains at amino acid positions 29 and 102, whereas the E7 protein exhibits one such domain at position 50. HPV-125 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of HPV-125, a quantitative type-specific real-time PCR was developed. The 95% limit-of-detection of the assay was 2.5 copies per reaction (range 1.7-5.7) and the intra- and inter-assay coefficients of variation were 0.47 and 2.00 for 100 copies per reaction, and 1.15 and 2.15 for 10 copies per reaction, respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (a total of 601 samples) showed that HPV-125 is a relatively rare HPV genotype, with cutaneous tropism etiologically linked with sporadic cases of common warts.
... However, different HPV types have site-specific tropism for mucosal or cutaneous epithelium; the high-risk mucosal a-HPVs are not found in cuSCCs, with the exception of genital and periungual tumors (Moy et al., 1989; Alam et al., 2003; Dubina and Goldenberg, 2009). Thus, many studies focus on detection of the cutaneous b-genus HPV types (b-HPV) in cuSCCs (Shamanin et al., 1994Shamanin et al., , 1996 Surentheran et al., 1998; Berkhout et al., 2000; Harwood et al., 2000; Forslund et al., 2003b; Asgari et al., 2008). The association of b-HPV with cuSCC is clearly defined for a specific group of patients with epidermodysplasia verruciformis , an autosomal recessive genodermatosis associated with susceptibility to b-HPV. ...
... However , the b-HPV types have not been firmly associated with cuSCC in the general population (IARC, 2007). b-HPV DNA is detected in 27–54% of SCCs from immunocompetent patients and 55–84% of SCCs from immunosuppressed patients (Shamanin et al., 1994Shamanin et al., , 1996 Berkhout et al., 1995 Berkhout et al., , 2000 Harwood et al., 2000; Forslund et al., 2003a Forslund et al., , 2007 Asgari et al., 2008). Indeed, in other studies, b-HPV has been detected with comparable frequency in normal skin, eyebrow hairs, and premalignant actinic keratoses (Boxman et al., 1997; Antonsson et al., 2000; Forslund et al., 2003b; Hazard et al., 2007; de Koning et al., 2007 de Koning et al., , 2009 Asgari et al., 2008). ...
... Taken together, this control specimen supports our impression of a-HPV as the driver and b-HPV as a mere passenger in periungual SCC. As in previous studies (Shamanin et al., 1994Shamanin et al., , 1996 Berkhout et al., 1995 Berkhout et al., , 2000 Boxman et al., 1997; Antonsson et al., 2000; Harwood et al., 2000; Forslund et al., 2003a Forslund et al., , b, 2007 Hazard et al., 2007; de Koning et al., 2007 de Koning et al., , 2009 Asgari et al., 2008), b-HPV DNA was detectable by nested PCR in 30% of SCCs, but was also found in a comparable proportion (28%) of normal skin samples. Moreover, we found extremely low viral loads in tumors that were positive for the viral genome. ...
β-Human papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCCs), but no mechanism of carcinogenesis has been determined. We used ultra-high-throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. In all, 67 cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific quantitative PCR. A total of 31 SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18-positive HeLa cervical cancer cell line and HPV16-positive primary cervical and periungual SCCs. Of the tumors, 30% (20/67) were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (P=0.310). Immunosuppression and age were significantly associated with higher viral load (P=0.016 for immunosuppression; P=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV16 and HPV18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCCs.
... HPV 3 and 10 are associated with plane, HPV 2 and 57 with common, and HPV 27 with intermediate warts [6]. HPV 77 has been found in tumours and warts of immunosuppressed but not in lesions of immunocompetent individuals [98]. HPV 2-associated warts have been most frequently found in the 20–40 years age group [53,54,99] , and in another study the prevalence of HPV 2/27/57- induced warts peaked at the age of 21–25 years [55]. ...
The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life.
... Multiplex Serology. The serum samples were tested for antibodies to the major capsid protein L1 of HPV 1, 5, 6, 8, 9, 10, 15, 16, 20, 24, 32, 36, 38, and 57 and to the early proteins E6 and E7 of HPV 8 and 38. We used multiplex serology, an antibody detection method based on a glutathione S-transferase capture ELISA, in combination with fluorescent technology (34-36).Table 2. Prevalence of antibodies against the major capsid protein L1 of 14 individual HPV types from A, B, and M papillomaviruses HPV type (species) SCC (n = 72), n (%) BCC (n = 160), n (%) Actinic keratosis (n = 81), n (%) Benign (n = 121), n (%) Total (N = 434), n (% DNA Analysis. ...
Cutaneous human papillomaviruses (HPV) are common in nonmelanoma skin cancers, benign skin lesions, and healthy skin. Increased seroprevalences for cutaneous HPV among nonmelanoma skin cancer patients have been described. To determine whether antibodies to cutaneous HPV are related to presence of the virus and/or to skin disease, we collected serum and biopsies from both lesions and healthy skin from 434 nonimmunosuppressed patients (72 squamous cell carcinomas, 160 basal cell carcinomas, 81 actinic keratoses, and 121 benign lesions). Biopsies were analyzed for HPV DNA by PCR, cloning, and sequencing. Serum antibodies to the major capsid protein L1 of HPV 1, 5, 6, 8, 9, 10, 15, 16, 20, 24, 32, 36, 38, and 57 as well as to the oncoproteins E6 and E7 of HPV 8 and 38 were detected using a multiplexed fluorescent bead-based assay. Type-specific seroprevalence among patients with the same type of HPV DNA (sensitivity of serology) varied from 0% to at most 28%. Presence of HPV DNA and antibodies to the same HPV type was not significantly correlated. However, seropositivity to any HPV type was significantly more common among patients positive for HPV DNA of any HPV type (odds ratio, 1.90; 95% confidence interval, 1.55-2.34). Seroprevalences were similar among the different patient groups but was, for most HPV types, somewhat higher among squamous cell carcinoma patients than among basal cell carcinoma patients (P < 0.01). In conclusion, additional studies are required to clarify the biological meaning of seropositivity as a marker of cutaneous HPV infection and skin disease.
... This method relies on detection of consensus primer PCR (GP5+/6+) products with type-specific oligonucleotide probes coupled to fluorescence-labelled polystyrene beads and allows detection of up to 100 different HPV types simul- taneously. Two non-hybridization typing methods following consensus PCR are sequence analysis of the PCR prod- uct [34,35] and restriction fragment length polymorphism (RFLP) analysis [36] . RFLP implies the digestion of consensus PCR products with restriction endonucleases , and comparison of the digestion pattern with those of known HPV types. ...
... The best known technique in this category is the commercially available, FDA-approved and clinically validated Hybrid Capture 2 (HC2) method [57]. This method uses a mixture of full-length RNA probes representing hrHPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Prior to the test, the clinical samples are heat-alkaline-denatured. ...
Given the causal relation between a persistent high-risk human papillomavirus (hrHPV) infection and the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer, hrHPV testing has been advocated in addition to cytology for the detection of clinically relevant cervical lesions. HrHPV testing is thought to improve cervical screening algorithms, the management of women with cytologically equivocal smears, and the management of women treated for high grade CIN. In this chapter we discuss different methods for HPV detection and genotyping and their respective applications.
... The risk of skin carcinoma increases with the duration of immunosuppression . However, currently it is not clear whether the risk is higher with some of these drugs, notably aziathioprime [9]. It seems that carcinogenic risk is more related to the degree of immunosuppression than to a specific immunosuppressive agent. ...
Renal transplantation has been performed for more than 35 years with a large success. However, the organ tolerance has to be associated with the induction and the maintenance of an immunosuppressive status in the patient which induces the development of skin cancers. Skin cancers are considered to be the most frequent tumours in transplant patients. The incidence of skin cancer is increased in transplant recipients as compared to the general population and varies according to the country concerned. Thus, Hartevelt et al. [1] found a cumulative incidence of skin cancer, ranging from 10 to 40% at 10 and 20 years after transplantation. This incidence is higher in Australians, 45 and 70% at 10 and 20 years, respectively, after the transplantation. This fact is related to more intense sun exposure at these latitudes. Among the skin cancers, cutaneous premalignant and malignant epithelial lesions (carcinoma) are the most frequent skin tumours in organ transplant recipients [2-4].
Skin cancers especially squamous cell carcinomas (SCC) are the most frequent malignancies in organ transplant recipients; they are often preceded by viral warts and solar keratoses and represent a model of viral carcinogenesis. They appear on sun-exposed areas, tend to be multiple and may have an aggressive course. Human papillomaviruses along with other co-carcinogenic factors such as ultraviolet radiation and immunosuppressive treatment seem to be involved in their development [1, 2].
