Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96

Abstract

Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The L1 open reading frame of HPV93 showed highest identity to HPV24 (79 %) and that of HPV96 had highest identity to HPV92 (71 %). Real-time PCR for HPV92, 93 and 96 on stripped biopsies from tumours and healthy skin from 269 immunocompetent patients found HPV DNA in 2.6 % of tumours and in 0.4 % of healthy skin samples. Double infections were observed in two tumours. HPV92 was detected in four, HPV93 in two and HPV96 in three tumours. The range of viral loads spanned from one copy per 45 cells to one copy per 10 000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study.Human papillomaviruses (HPVs) are epitheliotropic agents infecting both the genital tract and cutaneous tissue. High-risk types infecting the genital tract, e.g. HPV16, are recognized as important carcinogens (zur Hausen, 1996). HPV types infecting cutaneous tissue are the focus of investigation as possible carcinogenic agents of nonmelanoma skin cancer (NMSC). The NMSCs basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently occurring malignancies in Caucasian populations (Kiviat, 1999). Exposure to UV radiation is the major risk factor for development of NMSC, but increased risk is also observed among those with immunosuppressive treatment and fair skin type (Alam & Ratner, 2001). Cutaneous HPV infection is associated with NMSC in patients with the rare, hereditary disease epidermodysplasia verruciformis (EV) (Majewski & Jablonska, 1995;Orth, 1986) and about 20 distinct HPV types are found in lesions of these patients (Pfister & Ter Schegget, 1997). These HPV types can also be detected in lesions of immunocompetent patients as well as in healthy skin, making it difficult to assess the pathological significance of these viruses (Antonsson et al., 2000). However, HPV has been proposed as a co-factor for UV radiation in the development of NMSC (Akgul et al., 2006;Harwood et al., 1999).To date, over 100 HPV types have been characterized, but recently, a sensitive method, FAP PCR (Forslund et al., 1999), has detected about 130 additional putative cutaneous HPV types (Antonsson et al., 2000(Antonsson et al., , 2003aAntonsson & Hansson, 2002; Forslund et al., 1999 Forslund et al., , 2003bForslund et al., , 2004. Except for HPV92 (Forslund et al., 2003a), only subgenomic sequences are known of these putative HPV types. In this study, the complete genome sequences of two novel types, HPV93 and HPV96, were obtained by generating overlapping amplicons. HPV93 was described previously as FAIMVS6, originally identified in an actinic keratosis (AK) on the dorsum of the hand of an immunocompetent 82-year-old male (Forslund et al., 2003b). HPV96 was described previously as FA47 (Antonsson et al., 2003b) and was, in the current study, detected in a SCC in situ on...

Staphylococcus aureusand Squamous Cell Carcinoma of the Skin

“…HPV is known to be very commonly present in SCC but usually in very low amounts of virus (38)(39)(40). This is in line with our findings that MDA commonly amplifies S. aureus but only occasionally (a single tumor) amplifies HPV in SCC specimens.…”

Newly‐isolated HPV97, related to HPV18 and 45 is frequently detected in HIV‐positive men from the montreal area

“…Recently cloned types 92, 93, 94, 95 and 96 were isolated from skin lesions and belong to the cutaneous Beta Papillomavirus genus which has a less important influence on human health. [2][3][4][5] It was thus unusual that 2 independent research teams nearly simultaneously cloned and sequenced a novel HPV type that infects the anogenital mucosa, results that were presented by both groups at the 23rd International Papillomavirus Conference and Clinical Workshop 2006 in Prague. 6,7 We were greatly interested in the following article by Chen et al which was published on line March 9, 2007 in this journal 8 , on molecular characterization of HPV97 isolate cloned from a healthy Costa Rican women.…”

Characterization of seven novel human papillomavirus types isolated from cutaneous tissue, but also present in mucosal lesions

“…Several subsequent studies attempted to associate specific HPV types with the aetiology of non-melanoma skin cancer in immunosuppressed and immunocompetent patients (Shamanin et al, 1994(Shamanin et al, , 1996 Berkhout et al, 1995Berkhout et al, , 2000de Villiers et al, 1997;Forslund et al, 1999Forslund et al, , 2003bForslund et al, , 2007Asgari et al, 2008;Harwood et al, 2000Harwood et al, , 2004, whereas others demonstrated the presence of HPV in and on normal skin (Astori et al, 1998;Antonsson et al, 2000;Hazard et al, 2007;Chen et al, 2008). These studies all resulted in the identification of a vast spectrum of additional putative novel HPV types in the form of PCRamplified partial open reading frame (ORF) L1 sequences (Shamanin et al, 1996;de Villiers et al, 1997; Astori et al, 1998;Antonsson et al, 2000;Forslund et al, 2003a;.Full-length genomes of a relatively small number of these HPV isolates have been cloned and characterized (Delius et al, 1998;Forslund et al, 2003a;Vasiljevic et al, 2007Vasiljevic et al, , 2008. Definition of a papillomavirus type requires the isolation and characterization of a full-length genome in order to verify the genome organization characteristic of papillomaviruses (de Villiers et al, 2004a).…”

“…Full-length genomes of a relatively small number of these HPV isolates have been cloned and characterized (Delius et al, 1998;Forslund et al, 2003a;Vasiljevic et al, 2007Vasiljevic et al, , 2008. Definition of a papillomavirus type requires the isolation and characterization of a full-length genome in order to verify the genome organization characteristic of papillomaviruses (de Villiers et al, 2004a).…”