Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients (original) (raw)
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The Journal of infectious diseases, 2018
Findings from previous studies of cutaneous human papillomavirus (cuHPV) infection and keratinocyte carcinomas (KC) have varied due to several factors, including use of different sample types for cuHPV DNA detection. Elucidating the relationship between cuHPV infection in eyebrow hairs (EBH) and skin swabs (SSW) is critical for advancing the design of future studies. DNA corresponding to 46 beta and 52 gamma cuHPV types was measured in EBH and SSW obtained from 370 individuals undergoing routine skin cancer screening exams. Prevalence of beta/gamma cuHPV was 92%/84% and 73%/43% in SSW and EBH, respectively, with 71%/39% of patients testing positive for beta/gamma cuHPV in both sample types. Number of cuHPV types detected and degree of infection were correlated across SSW and EBH. When the EBH was positive for a given beta/gamma HPV type, the SSW was positive for that same type 81%/72% of the time. Testing SSW captures more cuHPV infection than EBH, with EBH infections usually repres...
Transplant International, 2019
To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV) and Lyon IARC polyomavirus (LIPyV), were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant vs. benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.
Journal of The National Cancer Institute, 1996
Background: Nonmelanoma carcinomas of the skin represent the most frequent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. Purpose: We analyzed tumors obtained from both immunosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. Methods: Twenty-nine specimens of nonmelanoma carcinomas of the skin were obtained from 19 renal allograft recipient patients; these included 20 specimens of squamous cell carcinoma (SCC) from 11 patients, five specimens of basal cell carcinoma (BCC) from four patients, and four specimens of carcinoma in situ (CIS) from four patients. Forty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four keratoacanthoma (benign epithelial tumor) specimens from four patients. A polymerase chain reaction method involving use of degenerate oligonucleotide primers, in which the conserved region of the open reading frame of the HPV LI (major capsid protein) gene is amplified, was used to amplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions; different primer combinations were used in order to increase the sensitivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specific DNA was either sequenced directly after elution from the gel or amplified with semi-nested, degenerate primers, after which the products were cloned and sequenced. Sequences were compared with all known papillomavirus sequences. Results: Thirteen (65%) of the 20 SCC specimens and three of the five BCC specimens from immunosuppressed (renal allograft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malignant tumor specimens from this patient group revealed faint signals upon amplification and hybridization; the origin of these signals has not been identified in the present study. In nonimmunosuppressed
The aim of this study was to determine whether detection of b-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that b-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the b-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that b-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.
Modern Pathology, 2014
The aim of this study was to determine whether detection of b-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that b-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the b-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that b-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.
British Journal of Dermatology, 2009
Background Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).Objectives We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.Methods One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.Results In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples (P = 0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) (P < 0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.Conclusions A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.
Case-Control Study of Cutaneous Human Papillomaviruses in Squamous Cell Carcinoma of the Skin
Cancer Epidemiology Biomarkers & Prevention, 2012
Background: Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin. Methods: To investigate the association between cutaneous HPV and SCC, a case-control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons. Results: SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23-3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22-2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14-2.84), 17 (OR, 1.59; 95% CI, 1.02-2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04-4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (
Cutaneous Human Papillomaviruses and Squamous Cell Carcinoma of the Skin: Nested Case–Control Study
Cancer Epidemiology, Biomarkers & Prevention, 2016
Background: Cutaneous human papillomavirus (HPV) types have been associated with non-melanoma skin cancer (NMSC), including a previous nested case-control study using HPV serology with bacterially derived fusion proteins with the major HPV capsid protein L1 (GST-L1). However, HPV serology using conformationally intact pseudovirions has been shown to correlate better with natural infection. Prospective studies using a more valid marker of infection are therefore warranted. Methods: Cancer registry follow-up of large Nordic biobanks identified prediagnostic serum samples from 633 subjects who later developed SCC, 1,990 subjects who developed basal cell carcinoma (BCC). The samples from cases and matched controls were tested for IgG to pseudovirions to 16 different HPV types