Prevailing papillomavirus types in non‐melanoma carcinomas of the skin in renal allograft recipients

Abstract

The role of human papillomavirus (HPV) in the aetiology of in situ and invasive carcinoma of the genital tract is well established. In the rare disorder epidermodysplasia verrucifor-mis (EV), in which patients develop extensive warts of unusual types and multiple cutaneous squamous cancers on light-exposed skin, current evidence suggests a probable role for a specific group of EV HPVs in the carcinogenic process. Determination of the possible role of HPV in the aetiology of non-melanoma skin cancers (NMSCs), which occur frequently in immunosuppressed organ allograft recipients, has been limited, until recently, by the lack of availability of a sensitive detection system for a wide range of cutaneous HPV types. We have used a combination of 2 sets of PCR primers to examine 68 benign and malignant tumours collected over a 12-year period from 25 renal allograft recipients. Cloning and sequencing of the PCR products were carried out to distinguish HPV DNA from cellular sequences. A combination of these techniques revealed HPV DNA in all viral warts, 65% of keratoses, 91% of intra-epidermal cancers and 91% of invasive squamous cancers. Both cutaneous and EV HPV types were detected, including 18 novel types. In 4 patients with multiple cancers, the most prevalent types were in the EV group: HPV 20, 23, 38 and 2 novel types, DL40 and DL267 (related to HPV 10 and 38, respectively). These 5 HPV types were present in a total of 73% of all malignant lesions tested. The technique described represents a reliable method of HPV DNA detection in NMSC. The EV group of HPVs predominate in the cancers, but the multiplicity of HPV types detected with double infection in some lesions suggests virus/virus in addition to virus/host interaction in the carcinogenic process. Int. The most frequently occurring cancer in Caucasians is non-melanoma carcinoma of the skin (Preston and Stern, 1992). Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) develop mainly on sun-exposed sites (Frost and Green, 1994), BCC outnumbering SCC by a ratio of 5:1 in immunocompetent populations. Organ allograft recipients commonly develop multiple skin lesions, such as warts, keratoacanthomas and keratoses, with progression to in situ or invasive SCCs, which occur mainly on sun-exposed sites (Penn, 1991). Patients with epidermodysplasia verruciformis (EV) also have a predisposition for extensive viral warts and non-melanoma skin cancers (NMSCs), especially SCC (Orth, 1987). In these tumours, a specific group of closely related papillomaviruses, thus far not commonly found in the general population, has been identified (Jablonska and Majewski, 1994). Human papillomavirus (HPV) 5 and HPV 8 DNA usually are found in those sun-exposed lesions which progress to carcinomas (Orth et al., 1979). A possible role for EV and other HPV types in the carcinogenic process in organ allograft recipients has been investigated over the past 12 years, but results have shown an enormous variation in the frequency and type of HPV DNA detected depending on the method employ...

Epidermodysplasia verruciformis–associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn

“…DL285, accession number Z95968 (77% homology to HPV 9), and DL287, accession number Z95969 (74% homology to HPV 24), were previously described by De Villiers et al 38 This study was approved by our institutional review board.…”

Hauterkrankungen bei organtransplantierten Patienten

“…In den malignen und prämalignen Hautveränderungen organtransplantierter Patienten sind DNA-Sequenzen einer Vielzahl unterschiedlicher humaner Papillomaviren nachweisbar [85,86,87]. Unter Verwendung sensitiver "broad range nested PCR-Techniken" ist die Diagnoserate HPV-positiver Tumore deutlich erhöht worden [88].…”

“…Die direkte pathogenetische Relevanz potenziell onkogener Virusinfektionen ist bis heute nicht eindeutig geklärt. Für eine Beteiligung humaner Papillomaviren in der Entwicklung maligner Hauttumoren spricht vor allem der Nachweis viraler DNA in bis zu 90% der kutanen Plattenepithelkarzinome transplantierter Patienten [87,99] und die Persistenz der HPV Infektion in benignen, prämalignen und malignen Hautläsio-nen bei Patienten nach Nierentransplantation [89]. Aus der Arbeitsgruppe von Alan Storey wurde kürzlich die Unterdrückung apoptotischer Prozesse durch die E6-Proteine einiger EV-assoziierter HPV-Typen beschrieben [96].…”

“…Aus der Arbeitsgruppe von Alan Storey wurde kürzlich die Unterdrückung apoptotischer Prozesse durch die E6-Proteine einiger EV-assoziierter HPV-Typen beschrieben [96]. Darüber hinaus sind UV-responsive Elemente in den Promotoren einiger HPV-Typen identifiziert worden [86,87]. UV-induzierte onkogene virale Proteine könnten daher die Proliferation infizierter Zellen durch Hemmung der Apoptose fördern.…”

Arsenic exposure and human papillomavirus response in non-melanoma skin cancer Mexican patients: a pilot study

“…Although no particular HPV types have been defined as predominant, the HPV types found were novel, including HPV-16, or not yet completely characterized (Forslund et al 1997;De Villiers et al 1997). On the other hand, it has been suggested that the toxic effects of chronic As exposure on the skin might be associated with HPV infection, since the rare HPV-41 was present in As-induced malignant lesions, such as squamous cell carcinomas and arsenical keratoses (Grimmel et al 1988).…”