Human Papillomavirus Infections in Nonmelanoma Skin Cancers From Renal Transplant Recipients and Nonimmunosuppressed Patients (original) (raw)
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Cancer research, 1994
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 sequences related to a number of epidermodysplasia verruciformis-associated HPV types. HPV DNA sequences were found in 14 (56%) of 25 biopsies from squamous cell and basal cell carcinomas. One squamous cell carcinoma contained HPV 41 DNA. A novel 640-base pair fragment sharing homology with HPV 29 (82.7%) was found in 15% (3 of 20) of squamous cell carcinomas, in 9.4% (3 of 32) of dysplastic warts and in 8.5% (4 of 47) common warts. The remaining positive carcinoma biopsies contained HPV-related DNA in such a low copy number that additional analysis is required. The identification of new HPV types in skin cancers of immunosuppressed patients (other than epidermodysplasia verruciforniis patients) further expands the spectrum of HPV-linked human malig nancies and permits new approaches to study the pathogenesis of skin cancers.
2006
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 sequences related to a number of epidermodysplasia verruciformis-associated HPV types. HPV DNA sequences were found in 14 (56% ) of 25 biopsies from squamous cell and basal cell carcinomas. One squamous cell carcinoma contained HPV 41 DNA. A novel 640-base pair fragment sharing homology with HPV 29 (82.7%) was found in 15% (3 of 20) of squamous cell carcinomas, in 9.4% (3 of 32) of dysplastic warts and in 8.5% (4 of 47) common warts. The remaining positive carcinoma biopsies contained HPV-related DNA in such a low copy number that additional analysis is required. The identification of new HPV types in skin cancers of immunosuppressed patients...
Journal of Investigative Dermatology, 2008
The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and nonsun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from β-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio = 4.0, confidence interval = 1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV βpapillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.
Journal of Clinical Virology, 2002
Background and objecti6es: A persistent infection by high-risk HPV is now considered as the major cause of cervical carcinoma. The use of a single cytological specimen for HPV DNA testing by two different molecular methods was analyzed and validated. Study design: HPV DNA testing by PCR-ELISA and hybrid capture II HPV test (HC-II), was investigated on 317 cytological samples obtained from Italian women. Two hundred twenty-seven women were referred to virological lab for HPV DNA testing during cytological routine screening and 90 during a cytological and virological follow-up after a conization or hysterectomy. Results: Overall, the concordance between the two assays was high (K =0.87). Compared with PCR-ELISA, the HC-II showed a sensitivity of 91.7% and a specificity of 95.4%. Although the analytical sensitivity of the PCR-ELISA was higher, the performance of the two tests did not differ in recognizing HPV DNA positive patients with either low or high-grade squamous intraepithelial lesions (LSIL or HSIL). HPV DNA positivity was directly correlated with the severity of cytological diagnosis (PB 0.005). Conclusions: In view of the comparable results obtained with the two assays and of the ease of use, and higher throughput of HC-II, it seems advisable, with a single cytological specimen, to employ the HC-II test as a first-line assay, either for screening or diagnosis, and to perform reflex PCR on positive samples, if typing of prevalent high risk HPVs is needed.
British Journal of Cancer, 2011
BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16 INK4a , a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16 INK4a expression in most SCC (Po0.001) and basal cell cancers (P ¼ 0.02), while almost all SCC in situ were p16 INK4a positive irrespective of HR-HPV presence (P ¼ 0.66). Diffuse p16 INK4a expression was associated with lack of pRB expression (P ¼ 0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16 INK4a expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and-negative lesions.
The EMBO journal, 1984
DNA of a new papillomavirus type was cloned from a cervical carcinoma biopsy. Two EcoRI clones of 7.8 and 6.9 kb in length were obtained, the latter contained a 900-bp deletion. The BamHI fragments of both clones were used to characterize the DNA. It represents a distinct type of papillomavirus as determined by its size, its cross-hybridization with DNA of other papillomavirus types under conditions of low stringency only, the co-linear alignment of its genome with HPV 6 and HPV 16 prototypes and its occasional occurrence as oligomeric episomes. We tentatively propose to designate it as HPV 18. DNA hybridizing with HPV 18 under stringent conditions was detected in 9/36 cervical carcinomas from Africa and Brazil, in 2/13 cervical tumors from Germany and 1/10 penile carcinomas. Benign tumors (17 cervical dysplasias, 29 genital warts), eight carcinomata in situ and 15 biopsies of normal cervical tissue were devoid of detectable HPV 18 DNA. HPV 18-related DNA was found, however, in cell...
British Journal of Dermatology, 2006
Background DNA of cutaneous human papillomavirus (HPV) types is frequently found in nonmelanoma skin cancer, and their E6 and E7 proteins can have transforming properties. Objectives To assess the biological activity of HPV types found in tumour tissues we examined HPV E6/E7 RNA expression and the antibody response to E6, E7 and L1 proteins. Methods Thirty-one snap-frozen biopsies from six immunosuppressed organ transplant recipients representing seven squamous cell carcinomas (SCCs), one basal cell carcinoma, four actinic keratoses (AKs), seven normal skin and 12 verrucae vulgaris (Vv) were analysed for 24 cutaneous HPV types by an L1 DNA polymerase chain reaction (PCR)-based method. The presence of E6/E7 transcripts of HPV 5, 8, 9, 15 and 20 was investigated by real-time reverse transcription-PCR. HPV DNA load was determined for HPV 8, 9 and 15 in 11 biopsies. Antibody response was measured by enzyme-linked immunosorbent assay using affinity-purified, bacterially expressed complete viral proteins fused to glutathione S-transferase as antigens. Results HPV DNA was detected in 25 of 31 tissue samples, indicating eight single and 17 multiple HPV infections. E6/E7 transcripts of HPV 8, 9 and 15 were found in low copy numbers in one SCC and three AKs, but not in normal skin or Vv. All four patients examined showed antibodies to cutaneous HPV antigens, but the antibody response did not correlate with E6/E7 expression detected in the tumour. Conclusions Transcriptional activity of the E6/E7 oncogenes in AK and SCC suggests an active role of HPV in the lesion.
Journal of Clinical Microbiology, 2001
We assessed the value of a new digoxigenin (DIG)-labeled generic probe mix in a PCR-enzyme-linked immunosorbent assay format to screen for the presence of human papillomavirus (HPV) DNA amplified from clinical specimens. After screening with this new generic assay is performed, HPV DNA-positive samples can be directly genotyped using a reverse blotting method with product from the same PCR amplification. DNA from 287 genital specimens was amplified via PCR using biotin-labeled consensus primers directed to the L1 gene. HPV amplicons were captured on a streptavidin-coated microwell plate (MWP) and detected with a DIG-labeled HPV generic probe mix consisting of nested L1 fragments from types 11, 16, 18, and 51. Coamplification and detection of human DNA with biotinylated -globin primers served as a control for both sample adequacy and PCR amplification. All specimens were genotyped using a reverse line blot assay (13). Results for the generic assay using MWPs and a DIG-labeled HPV generic probe mix (DIG-MWP generic probe assay) were compared with results from a previous analysis using dot blots with a radiolabeled nested generic probe mix and type-specific probes for genotyping. The DIG-MWP generic probe assay resulted in high intralaboratory concordance in genotyping results (88% versus 73% agreement using traditional methods). There were 207 HPV-positive results using the DIG-MWP method and 196 positives using the radiolabeled generic probe technique, suggesting slightly improved sensitivity. Only one sample failed to test positive with the DIG-MWP generic probe assay in spite of a positive genotyping result. Concordance between the two laboratories was nearly 87%. Approximately 6% of samples that were positive or borderline when tested with the DIG-MWP generic probe assay were not detected with the HPV type-specific panel, perhaps representing very rare or novel HPV types. This new method is easier to perform than traditional generic probe techniques and uses more objective interpretation criteria, making it useful in studies of HPV natural history.