Prevalence of human papillomavirus DNA in cutaneous neoplasms from renal allograft recipients supports a possible viral role in tumour promotion

Stark, Lesley A.; Arends, Mark J.; McLaren, K M; Benton, E. C.; Shahidullah, Hossain; Hunter, John; Bird, C. C.

doi:10.1038/bjc.1994.43

Cited by 86 publications

(59 citation statements)

References 49 publications

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“…Resolving this question is difficult because of the large number of human papillomaviruses, ignorance of their potential pathogenic mechanisms and the problem of providing evidence for other as yet uncharacterized viruses (Stark et al, 1994;Tieben et al, 1994). The results presented, while compatible with a role for viral pathogenesis, are puzzling in at least one respect.…”

Section: Resultsmentioning

confidence: 96%

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

Rehman

Quinn²,

Takata³

et al. 1997

Br J Cancer

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Summary Organ transplant recipients receiving immunosuppression show a dramatically increased risk of non-melanoma skin cancer. The cause of this increase is not known. We report that the rate of loss of heterozygosity (at all the loci we examined) was significantly lower in tumours from immunosuppressed individuals than in tumours from immunocompetent subjects [20 out of 148 (14%) vs 157 out of 428 (37%); P < 0.0001]. These results suggest that tumours in immunosuppressed individuals have a different molecular pathogenesis.Keywords: loss of heterozygosity; non-melanoma skin cancer; immunosuppression; tumour suppressor; human papilloma virus; squamous cell carcinoma Patients receiving immunosuppressive therapy after organ transplantation show up to a 250-fold increase in the incidence of nonmelanoma skin cancers (NMSCs) and their precursor lesions (Abel, 1989; Hartevelt et al, 1990; Espana et al, 1995; Glover et al, 1997). In such patients the high prevalence of infection by a spectrum of human papilloma virus (HPV) types together with a high incidence of other neoplasms associated with a viral pathogenesis has suggested a role for virus during NMSC development (Barr et al, 1989). However, in skin, unlike cervical carcinoma, compelling evidence that HPVs play a causative role, rather than being mere passengers, is lacking. It is also possible that other viruses such as the recently described Kaposi's sarcoma herpes-like virus (KSHV) (Boshoff et al, 1996) or as yet unidentified viruses may be important. We therefore sought indirect evidence for a different molecular pathogenesis in these tumours that would provide support for a causal role for one or more types of virus, including viruses that had not yet been identified.Tumour-suppressor gene inactivation commonly occurs by mutation of one allele accompanied by chromosome loss of the wild-type allele (Knudson, 1991). Other mechanisms of tumoursuppressor gene activation can occur, including binding of the products of virally encoded oncogenes or changes in methylation status of tumour-suppressor genes (Vousden, 1993;Kinzler and Vogelstein, 1996). If, in tumours from immunosuppressed individuals, tumour-suppressor genes are being inactivated by alternative means, then the rate or pattern of loss of heterozygosity might be expected to differ from those in immunocompetent individuals. We examined this hypothesis. Ten-micrometre tissue sections were carefully microdissected to separate tumour from adjacent normal epithelium, and the DNA was extracted using phenol-chloroform (Jackson et al, 1995). In all cases, control DNA from either adjacent normal skin or blood was used. Tumour and control DNA was subject to polymerase chain reaction (PCR) amplification using one [y-32P]ATP (Life Sciences, Amersham, UK) end-labelled primer as previously described (Rehman et al, 1996), using microsatellite markers 3p (D3S1293), 9p (D9S162, D9S171), 9q (D9S197), 13q (D13S170), 17p (D17S796) and 17q (D17S785) (Research Genetics, Huntsville, AL, USA). PCR products were resolved on a ...

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Section: Resultsmentioning

confidence: 96%

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

Rehman

Quinn²,

Takata³

et al. 1997

Br J Cancer

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“…Papillomatosis of the skin (Gregory et al, 1986;Ruehl et al, 1987;Seibel et al, 1989a) and gingiva (Seibel et al, 1989b) was noted as one of several complications of cyclosporin-A therapy; however, no papillomaviral DNA or antigen was demonstrated (Seibel et al, 1989a). Prolonged or severe papillomavirus infections were reported in human patients immunosuppressed by either human immunodeficiency virus infection or iatrogenic means (Stark et al, 1994;Benton and Arends, 1996).…”

Section: Immunity To Papillomavirus Infectionsmentioning

confidence: 99%

Canine Papillomavirus—A Centenary Review

Nicholls

Stanley

1999

Journal of Comparative Pathology

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“…Renal transplant recipients given immunosuppressive therapy for long periods of time have an increased incidence of cutaneous neoplasia (2,10,29). Also, more than 90% of kidney recipients develop skin warts and 40% develop skin cancer within 15 years of transplantation, a 50-to 100-fold increase compared to the general population (7), and EV-associated HPV types have been found in skin tumors from such patients (5,12,16,21,28).…”

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confidence: 99%

The Ubiquity and Impressive Genomic Diversity of Human Skin Papillomaviruses Suggest a Commensalic Nature of These Viruses

Antonsson¹,

Forslund²,

Ekberg

et al. 2000

J Virol

362

389

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Human papillomaviruses (HPV) are epitheliotropic viruses, with some types suggested to be associated with skin cancer. In this study, swab samples collected from five different sites on the skin of renal transplant recipients, dialysis patients, and age-and sex-matched healthy controls were analyzed for HPV DNA by a newly designed PCR test. Most individuals were found to have asymptomatic HPV infections; more specifically, 94% of the renal transplant patients, 82% of the dialysis patients, and 80% of the healthy controls were positive for HPV DNA. The multiplicity of the HPVs detected was astounding: 20 previously described and 30 putatively new types were identified by cloning and sequencing of 33 samples from 13 individuals. These results demonstrate that normal human skin harbors an array of papillomaviruses, most of them previously unknown.To date, 85 different genotypes of the human papillomaviruses (HPV) have been fully characterized. In addition to being the causative agents of common skin warts, there is evidence that certain types of HPV play a role in the pathogenesis of skin cancer associated with the rare hereditary disease epidermodysplasia verruciformis (EV) (22, 27), and they are therefore designated EV-associated HPV.Renal transplant recipients given immunosuppressive therapy for long periods of time have an increased incidence of cutaneous neoplasia (2,10,29). Also, more than 90% of kidney recipients develop skin warts and 40% develop skin cancer within 15 years of transplantation, a 50-to 100-fold increase compared to the general population (7), and EV-associated HPV types have been found in skin tumors from such patients (5,12,16,21,28). Interestingly, EV HPV types have also been detected in hairs plucked from normal skin of 94% of renal transplant recipients (8) and 67% of healthy controls (9), and in another study (1), 35% of biopsy specimens of normal skin obtained during cosmetic surgery were positive for HPV DNA.In a recent report (20), we presented a PCR test that holds promise as a potent tool for exploring HPV both in skin tumors and in normal skin. In the present investigation, we used the test to study the presence of HPV at various sites on normal skin of both renal patients who were or were not on immunosuppression and matched healthy controls, and there is a serendipitous aspect to the results. MATERIALS AND METHODSSubjects. We studied 52 of about 130 renal transplant recipients being followed up at the outpatient clinic of nephrology of Malmö University Hospital, Malmö, Sweden. The median time since transplantation was 5 years and 2 months, and the range was 2 months to 26 years. Also included in the study were 28 of the 67 patients being treated at the Dialysis Unit; the median length of dialysis treatment was 2 years and 5 months (range, 1 month to 14 years). All of the transplant and dialysis patients were randomly selected, and a sex-and age-matched healthy control was recruited for each of the patients. The age range of the individuals in the three groups was 21 to 80 years,...

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Prevalence of human papillomavirus DNA in cutaneous neoplasms from renal allograft recipients supports a possible viral role in tumour promotion

Cited by 86 publications

References 49 publications

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

Low frequency of allelic loss in skin tumours from immunosuppressed individuals

Canine Papillomavirus—A Centenary Review

The Ubiquity and Impressive Genomic Diversity of Human Skin Papillomaviruses Suggest a Commensalic Nature of These Viruses

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