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

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of species 2 from skin lesions designated HPV-107, -110 and -111 and FA75[KI88-03], an isolate of an unpublished HPV type, and analysed their prevalence and viral loads in biopsies from SCC, actinic keratosis (AK), basal cell carcinoma, seborrhoeic keratosis and the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 HPV-107, -110 and -111 and FA75[KI88-03] 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.

Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96.

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 papillomavirus subtypes are not uncommon.

While both variants and types of human papillomavirus (HPV) are common, subtypes (2-10% sequence divergence in the L1 gene) have been considered to be rare. We searched GenBank and in-house databases using a 440 nt L1 fragment and identified 7, 30 and 10 subtypes/putative subtypes in the HPV genera Alpha, Beta and Gamma, respectively. The number of types/putative types in each genus was 54, 58 and 103. Thus, there appears to exist at least 47 different subtypes/putative subtypes of HPV and they seem to be particularly common in the genus Beta-papillomavirus.

Cutaneous human papillomaviruses persist on healthy skin.

Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.

Subtype HPV38b[FA125] demonstrates heterogeneity of human papillomavirus type 38.

The human papillomaviruses (HPVs) exist as more than 100 distinct types. While variants of HPV are common, only few HPV subtypes have been reported. HPV type 38 has been proposed to be associated with nonmelanoma skin cancer (NMSC), with reported prevalences of up to 55%. A subtype of HPV38 was cloned, completely sequenced and found to have a 96% sequence similarity to prototype HPV38 in the L1 open reading frame. The presence of prototype HPV38 and HPV38b[FA125] was examined in paired biopsies of tape-stripped skin lesions and healthy skin from 269 immunocompetent patients by real-time PCR. Prototype HPV38 and HPV38b[FA125] were present in seven (3%) and five (2%) lesions, respectively, in viral loads ranging from one copy per 150 cells to one copy per 70,000 cells. In summary, we found that HPV38 is heterogeneous and is one of so far only few HPVs that contain subtypes. The heterogeneity needs to be considered in studies of the biology of this virus.

Prevalence and type spectrum of human papillomaviruses in healthy skin samples collected in three continents.

In order to investigate whether previous findings of ubiquitous skin papillomavirus infection in Caucasians apply to populations from other parts of the world, skin swab samples from Bangladesh, Japan, Ethiopia and Zambia were analysed in parallel with Swedish samples. The prevalence of HPV DNA in the material from Bangladesh was 68 %, Japan 54 %, Ethiopia 52 %, Zambia 42 % and Sweden 70 %. A great multiplicity of genotypes was demonstrated by the finding of 88 HPV types or putative types in 142 HPV DNA-positive samples in total. Double or multiple genotypes were frequently found in the same sample. The most prevalent HPV type was HPV-5, with an overall prevalence of 6.5 %. This was also the only type that was found in samples from all of the countries in the study. The results presented show that commensal skin HPV infections have a worldwide distribution with a very broad spectrum of genotypes.