Human Papillomavirus Gene Expression in Cutaneous Squamous Cell Carcinomas from Immunosuppressed and Immunocompetent Individuals

Abstract

Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of 10 (40%) OTR warts. In mixed infections transcripts for both types were detected in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression in SCC; although only a proportion of tumors were positive, the similarly low transcriptional activity in warts suggests this is an underestimate. These observations, together with emerging epidemiological and functional data, provide further reason to focus on the contribution of EV-HPV types to the pathogenesis of cutaneous SCC.

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

“…22,[35][36][37][38][39][40][41][42][43] Despite these findings, a causal role of these viruses has been difficult to verify because of their ubiquitous prevalence in the general population and their absence in some cancers. 25,44 The major weakness of the available studies is that the proposed association is mostly based on the presence of viral DNA in tumor tissues or positive antibody responses. Very few studies have addressed whether the b-HPV detected in these cases are actually localized within the malignant cells or whether they are transcriptionally active, the confirmation of which would greatly strengthen the evidence for a carcinogenic role of these pathogens.…”

The EVER Proteins as a Natural Barrier against Papillomaviruses: a New Insight into the Pathogenesis of Human Papillomavirus Infections

“…Among the beta-HPVs, HPV5 and HPV8 are classified as high-risk genotypes since they are associated with skin carcinomas occurring in EV patients (151,152). It is worth stressing that beta-HPVs have been detected in trace amounts in a large proportion of nonmelanoma skin carcinomas (NMSCs) of non-EV patients, particularly those carcinomas that develop in immunocompromised individuals (57,153,165,171,202). Moreover, it has been suggested that these viruses may contribute to skin tumors in immunocompetent individuals (75), and a possible role of beta-HPV in skin carcinogenesis constitutes a hot research topic (35,76,153).…”

Genetics of Epidermodysplasia Verruciformis

“…In both immunocompetent and immunosuppressed non-EV patients these viruses are also frequently found; however, only very low copy numbers (usually below one copy per cell) were detected in actinic keratosis, SCC, basal cell carcinoma, and perilesional skin [48]. It has been shown that beta PV are transcriptionally active in benign and malignant lesions of EV patients [49,50] and also in 3 of 4 actinic keratosis and 5 of 18 SCC of immunosuppressed non-EV patients [51,52].…”