A Potentially Oncogenic Human Papillomavirus (HPV-5) Found in Two Renal Allograft Recipients

Abstract

We have observed 2 immunosuppressed renal allograft recipients with skin lesions induced by human papillomavirus type 5 (HPV-5). One recipient had multiple pityriasis versicolor-like (PV-like) skin lesions on his arms and trunk, and multiple Bowenoid in-situ skin cancers. The other had 2 warty lesions on the back of her fingers. Structural antigens of human papillomavirus type 5 (HPV-5) were identified in benign lesions from both patients by immunofluorescence. The histologic and ultrastructural features observed in lesions from both patients were similar to those previously seen in HPV-5-induced lesions occurring in patients with the rare disease epidermodysplasia verruciformis (EV). The severe form of EV is characterized by HPV-5-induced PV-like lesions, multiple skin cancers, and usually depressed cell-mediated immunity. The picture seen in one of our renal allograft recipients recalls this severe form of EV. HPV-5, until now, has been found only in EV patients. The role of this potentially oncogenic virus in skin cancers which are known to occur with increased frequency in immunosuppressed renal allograft recipients must be determined.

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

“…By contrast, investigation of the relationship between HPV and cutaneous cancers in RARs has been inconclusive with regard to both prevalence and type of HPV DNA detected. This may be the result of differences in sample size studied or differences in sensitivity and specificity of the detection (Lutzner et al, 1980(Lutzner et al, , 1983Rudlinger et al, 1986;Jablonska et al, 1987;Van der Leest, 1987;Blessing et al, 1989;Euvrard et al, 1991). An additional factor in some studies may be the inclusion of a large proportion of patients who seem to be at exceptionally high risk of developing multiple and widespread premalignant and malignant cutaneous lesions with increased HPV DNA content .…”

“…Moreover, all 15 positive specimens in that study came from four patients at exceptionally high risk of development of cutaneous lesions, each of whom had multiple SCCs. The balance of evidence now suggests that HPV 5 and 8 DNA is found relatively infrequently in tumours from RARs (Lutzner et al, 1980(Lutzner et al, , 1983Rudlinger et al, 1986;Van der Leest, 1987;Soler et al, 1992).…”

“…Histologically, viral warts and keratotic lesions in RARs often exhibit varying degrees of epidermal dysplasia, while SCCs develop on a background of verrucous keratoses and may retain HPVassociated features. However, the detection of HPV DNA in the cutaneous SCC of RARs has been somewhat controversial, with EV-associated types and a variety of common cutaneous and genital HPV types being identified in some, but not all, studies (Lutzner et al, 1980;Van der Leest et al, 1987;Barr et al, 1989;Dyall-Smith et al, 1991;Soler et al, 1992).…”

Molecular Mechanisms of Ultraviolet Radiation Carcinogenesis

“…These studies suggest a mechanism by which carcinogenesis may result from UV activation of the papilloma virus DNA sequences, or cooperation between the effects of the papilloma virus DNA gene products and a separate change induced by UV radiation to induce the neoplastic state. It is interesting to note that human papilloma viral DNA sequences have been detected in hyperkeratotic lesions from sun-damaged skin (Spradbrow et al, 1983), in KA and malignant melanoma (Scheurlen et al, 1986), in patients with epidermodysplasia verruciformis (Lutzner et al, 1984;Orth et al, 1979) and in immunosuppressed patients (Lutzner et al, 1980). Further, progression to malignancy in epidermodysplasia patients occurred only in the lesions on sun-exposed body sites.…”

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy

“…These studies reported the detection of HPV 5 and 8 in small numbers of cases that often included highly selected individuals, such as patients with multiple SCCs (Lutzner et al, 1980(Lutzner et al, , 1983Van der Leest et al, 1987;Barr et al, 1989;Blessing et al, 1990). Negative results were reported in a number of studies; many are explicable by the use of less than ideal substrates, such as DNA from formalin-fixed tissue or suboptimal techniques, such as reverse blotting or dot-blot hybridization (Rudlinger and Grob, 1989;Blessing et al, 1990;Dyall-Smith et al, 1991;Smith et al, 1993;McGregor et al, 1994), or the use of PCR with LI consensus primers that were designed primarily for detection of anogenital rather than cutaneous HPV types.…”