Four novel human betapapillomaviruses of species 2 preferentially found in actinic keratosis

Abstract

Recent studies have suggested an association between human papillomaviruses (HPVs), particularly species 2 members of the genus Betapapillomavirus, and squamous cell carcinoma (SCC) of the skin. As most of these viruses are uncharacterized, molecular characterization and epidemiology are needed to advance our understanding of their significance in carcinogenesis. This study determined the complete genomes of four betapapillomaviruses of species 2 from skin lesions designated , an isolate of an unpublished HPV type, and analysed their prevalence and viral loads in biopsies from SCC, actinic keratosis (AK), basal cell carcinoma, seborrhoeic keratosis and the healthy skin of 263 immunocompetent patients by HPV type-specific real-time PCR assays. Seventeen patients (6.5 %) harboured at least one of the four HPV types in their lesion, whereas seven patients (2.7 %) harboured one or more of the HPV types in healthy skin. Overall, the four viruses were more common in AK than in healthy skin (odds ratio 5.0, 95 % confidence interval 1.4-17.5), but the prevalence and viral loads were low. This characterization of expands the heterogeneity of members of species 2 of the genus Betapapillomavirus. However, as these types were found in only a few samples and in low amounts, a possible role in carcinogenesis remains elusive.

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.…”

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

“…The sequence of HPV 100 L1 is 79 % identical to the L1 ORFs of both HPV 22 and HPV 23. The HPV 104 ORF L1 nucleotide sequence is 78 % identical to that of HPV 107, and the HPV 113 ORF L1 nucleotide sequence is 83 % identical to that of HPV 111 (Vasiljevic et al, 2008) and 78 % identical to that of HPV 9. (94) 82 (89) 79 (86) 79 (87) 78 (85) 80 (86) 83 (92) L2 88 (91) 79 (86) 82 (90) 74 (72) 71 (70) 77 (85) 77 (86) 83 (90) E1 91 (92) 83 (83) 87 (88) 83 (82) 83 (81) 80 (81) 85 (87) 86 (88) E2 91 (89) 75 (80) 80 (76) 75 (76) 78 (85) 74 (73) 72 (71) 88 (86) E6 90 (88) 85 (88) 81 (81) 76 (79) 79 (79) 75 (75) 78 (73) 84 (86) E7 95 (94) 87 (89) 85 (81) 84 (82) 79 (74) 79 (78) 83 (86) 90 (96) *E6 uses the second ATG.…”

“…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).…”

“…The seven types and the respective partial L1 sequences on which they were identified are as follows: HPV 94 (DL40), HPV 98 (GA1-3), HPV 99 (GA3-1), HPV 100 (DL267), HPV 104 (DL253), HPV 105 (DL294) and HPV 113 (DL250). An additional partial sequence, DL285 (de Villiers et al, 1997), forms part of the recently described HPV 107 (Vasiljevic et al, 2008). Patient samples that had, over the course of 20 years, been identified as harbouring the respective partial putative novel HPV type were used for rolling-circle amplification.…”

“…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).…”