Detection of human papillomavirus in skin and genital lesions of renal allograft recipients by in situ hybridization.

Renal allograft recipients have an increased incidence of malignancy including squamous carcinoma of cervix and skin. There is growing evidence that human papillomavirus (HPV) has a part to play in malignant transformation at these sites. We have previously identified HPV DNA in the skin and genital lesions of such patients by dot and Southern blotting. In situ hybridization studies, using biotinylated DNA probes for HPV 4, 5 and 8 in skin lesions and 6, 11, 16 and 18 in genital lesions, were performed on tissues derived from the same group of patients. In the cutaneous lesions, only 25% of the specimens probed were found to contain virus by in situ hybridization; 60% of these specimens were found to harbour virus by dot and Southern blotting. In situ hybridization revealed HPV 16 and/or 18 in 86% of the genital lesions probed.

The prevalence of skin disorders in renal allograft recipients receiving cyclosporin A compared with those receiving azathioprine.

Ninety-four renal allograft recipients receiving cyclosporin A (CsA) immunosuppression for up to 4 years were examined for the presence of viral warts, keratoses, and skin cancers. They were compared with a group of 68 recipients on azathioprine who had been matched for duration of immunosuppression and other factors that might influence the occurrence of these lesions. No difference in prevalence of these tumours was found. Viral, bacterial, and fungal infections and other disorders of the skin related to immunosuppression were also noted. Apart from hypertrichosis, which occurred more frequently in the CsA group, no differences were observed. In view of the importance of duration of immunosuppression, the relative effects on the skin of the two drugs will not become apparent until CsA has been in general use for a much longer period of time. In the early stages, however, there appear to be no differences in the dermatological side-effects between CsA- and azathioprine-treated patients.

Histopathology of skin lesions in renal allograft recipients--an assessment of viral features and dysplasia.

We report the pathology of benign and malignant skin lesions from 13 renal allograft recipients. The 59 lesions included 18 squamous carcinomas, 16 verrucous keratoses, 19 warts with varying dysplasia, three plaque lesions resembling those found in epidermodysplasia verruciformis, two non-specific keratoses and one basal cell carcinoma. We delineate criteria for histological assessment of the presence of human papilloma virus (HPV) and use the term verrucous keratosis for lesions in which there is a putative viral contribution. Our findings emphasize the lack of correlation between clinical and histological assessment of the lesions. We note the variable and significant dysplasia within otherwise typical viral warts and the architectural features suggestive of HPV presence in the dysplastic lesions and in in situ and invasive squamous carcinomas. Parallel virological studies have revealed the presence of HPV 5/8 in over 60% of the invasive and in situ carcinomas probed. These HPV types have previously been isolated from squamous carcinomas of epidermodysplasia verruciformis, a condition whose defective cell-mediated immunity may be compared with that of the immunosuppression in our patients.

Human papilloma virus infection and skin cancer in renal allograft recipients.

202 renal allograft recipients in south-east Scotland, who had received transplants between 1965 and 1986, were monitored over 3 years (1984-87) for the presence of warts, keratoses, and skin cancers. 77% of 69 patients with graft survival of more than 5 years had viral warts, 38% had keratoses, and 12% had skin cancers, whereas of the 133 with graft survival of less than 5 years 20% had warts, 17% had keratoses, and 1.5% had skin cancers. The ratio of squamous cell carcinoma to basal cell carcinoma was 15:1. Most viral warts showed significant epidermal dysplasia, and keratoses and squamous cell carcinomas had signs of human papilloma virus infection. 15 (60%) of 25 squamous cell carcinomas contained HPV5/8 DNA and 1 contained HPV4 DNA--HPV5/8 DNA was detected in skin lesions of recipients with cancers significantly more often than in those matched for duration and type of immunosuppression with nonmalignant skin lesions. The findings suggest a role for HPV5/8 in the aetiology of squamous cell carcinoma in renal allograft recipients.

Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts.

An increased prevalence of cervical cancer has been observed in immunosuppressed women, but controlled studies are rare. Biopsy specimens from 49 women with renal allografts and 69 non-immunosuppressed controls (with no history of cervical intraepithelial neoplasia, vulval warts, or abnormal results of cervical smear tests) were assessed for colposcopic appearance, cytological and histological diagnosis, and the presence of human papillomavirus types 6/11 and 16/18 DNA sequences. At colposcopy 26 (53%) of the women with allografts had cervical abnormalities compared with 20 (29%) of the controls. The prevalence of cervical intraepithelial neoplasia was significantly higher in the women with allografts (24 (49%) compared with 7 (10%]. The overall rate of detection of human papillomavirus DNA did not differ significantly between the two groups. There was however, a significant difference in the rate of detection of human papillomavirus type 16/18 DNA (27% in the women with allografts and 6% in the controls). These data confirm that pathological and virological changes affecting the cervix are significantly increased in immunosuppressed women and emphasise the need for regular colposcopic examination.

Determination of glycosylated adult and foetal haemoglobins by affinity chromatography.

Estimation of adult glycosylated haemoglobin by affinity chromatography was found to be quick and less dependent on ionic strength, pH and temperature than ion-exchange chromatography. Results obtained by both procedures correlated strongly (r = 0.96) but the range for normal subjects was smaller with the affinity assay. The affinity method correlated equally well with the colorimetric assay (r = 0.95). However, the method did not measure all the glycosylated forms, and only half of the glycosylated species isolated by ion-exchange chromatography was bound to the affinity resin. It also showed that the amount of glycosylated haemoglobin in cord blood is less than in adult blood.