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Approximately 40% of vulvar squamous cell carcinoma (vSCC) cases are etiologically associated with high-risk human papillomaviruses (HPVs) of the alpha genera (α-HPV) that cause other anogenital cancers; however, the etiology of α-HPV-negative vSCC is poorly understood. HPVs of the beta genera (β-HPV) are risk factors for cutaneous squamous cell carcinoma (cSCC) and may be related to carcinomas originating in other cutaneous sites such as the vulva. In this study, we investigate the presence of β-HPVs, with an emphasis on p16-negative squamous lesions adjacent to vSCC. We subjected 28 vulvar squamous intraepithelial lesions adjacent to vSCC for comprehensive HPV genotyping, p16 and p53 immunohistochemistry, and consensus morphology review. Selected cases were subjected to qPCR and RNA in situ hybridization. Clinical data were obtained from medical records. β-HPV DNA was detected in eight of ten p16-negative lesions and three of fourteen p16-positive high-grade squamous intraepithelial lesions. The HPV DNA loads in vulvar squamous intraepithelial lesions ranged between less than 1 HPV DNA copy per cell to more than 100 HPV DNA copies per cell. This is, to the best of our knowledge, the first report of the association of p16-negative vulvar intraepithelial squamous lesions with detection of β-HPVs. These findings expand possible etiologic mechanisms that may contribute to p16-negative lesions of the vulva.

Background: Three genera of human papillomavirus (HPV) infect the oral cavity and oropharynx- alpha (α), beta (β) and gamma (γ). While α-HPV infection is an established risk factor for head and neck cancers (HNC), the role of other genera remains unclear. We aimed to estimate the effect of α-, β-, γ-HPV on HNC using a hospital-based case-control study., Methods: We recruited incident HNC cases (396) and controls (439), frequency-matched by age and sex from four main referral hospitals in Montreal, Canada. We collected information on sociodemographic and behavior characteristics using in-person interviews, and tested rinse, brush and tumor specimens for HPV genotypes. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the effect of HPV on HNC using logistic regression, adjusting for confounding. We conducted probabilistic bias analysis to account for potential exposure misclassification, selection bias, and residual confounding., Results: α-HPV genus had a strong effect on HNC, particularly HPV16 (aOR=22.6; 95% CI: 10.8, 47.2). β-HPV was more common among controls (aOR=0.80; 95% 0.57, 1.11). After adjustment for HPV16, we found weaker evidence for γ-HPV (aOR= 1.29; 95% CI: 0.80, 2.08). Combined bias analyses for HPV16 increased the strength of the point estimate, but added imprecision (aOR=54.2, 95% CI: 10.7, 385.9)., Conclusions: α-HPV, especially HPV16, appears to increase the risk for HNC, while there is little evidence for an effect of β- or γ-HPV. β-HPV may have a preventive effect, while γ-HPV may increase the risk of HNC, although to a lesser extent than that of α-HPV. Results for cutaneous HPV were imprecise and less conclusive. Due to possible epidemiologic biases, the true relation between HPV and HNC could be underestimated in the literature. Further improvement in current methods and more studies of the biologic mechanisms of the three genera in HNC development are warranted., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oral infection by Human Papillomavirus (HPV) has recently gained great attention because of its involvement in the development of a subset of head and neck squamous cell carcinoma. The role of specific Alpha-HPVs in this regard has been well established, whereas the contribution of other genera is under investigation. Despite their traditional classification as "cutaneous" types, Beta and Gamma HPVs are frequently detected in oral samples. Due to the lack of a standardized protocol, a large variety of methodologies have been used for oral sample collection, DNA extraction, HPV detection and genotyping. Laboratory procedures influence the evaluation of oral HPV prevalence, which largely varies also according to the population characteristics, e.g., age, gender, sexual behavior, Human Immunodeficiency Virus (HIV) status. Nevertheless, oral infection by Beta and Gamma HPVs seems to be even more common than Alpha-HPVs. The latter is 5-7% in the general population, and increases up to 30% approximately in HIV-infected men who have sex with men. Despite major advances in the evaluation of oral HPV prevalence, its natural history is still little understood, especially for Beta and Gamma HPVs. The latest technologies, such as Next Generation Sequencing (NGS), can be exploited to gain new insights into oral HPV, and to improve the identification of novel HPV types.

Introduction: Basal cell carcinoma (BCC) is the most common skin cancer in the Caucasian population. It is believed that infections caused by viruses from the genus betapapillomavirus (β-HPV) might be associated with the risk of BCC, but the spread of data on the prevalence of the virus in biopsies is significant., Aim: To assess the presence and diversity of β-HPV in skin samples taken from the tumour and a fragment of healthy skin from the patients with BCC, as well as checking the correlation of factors listed below and presence of β-HPV infection in the studied patients., Material and Methods: The study was conducted on the skin biopsies from 73 patients with histopathologically confirmed BCC. The following data were collected from patients: sex, age, hair colour and tumour location. Using the polymerase chain reaction (PCR) test, the presence of β-HPV infection was detected in the tested samples. PCR and reverse hybridization assay were also used to genotype 25 types of β-HPV., Results: A statistically significant correlation was found between the sex and BCC type, BCC type and tumour location, BCC type and exposure to UV radiation, as well as between the hair colour and tumour location. The correlation between the BCC type and the number of tumours and HPV types detected was also noted., Conclusions: Preliminary studies suggest that one of the risk factors for development of infiltrating lesions is the presence of a single HPV 93 infection, but further research is needed to confirm these assumptions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia Sp. z o. o.)

Human papillomavirus type 8 (HPV8) is associated with the development of non-melanoma skin cancer. In the past we already delved into the mechanisms involved in keratinocyte invasion, showing that the viral E7 oncoprotein is a key player that drives invasion of basal keratinocytes controlled by the extracellular protein fibronectin. To unravel further downstream effects in E7 expressing keratinocytes we now aimed at characterizing gene and protein/phosphoprotein alterations to narrow down on key cellular targets of HPV8-E7. We now show that gene expression of GADD34 and GDF15 are strongly activated in the presence of E7 in primary human keratinocytes. Further analyses of fibronectin-associated factors led to the identification of the Src kinase family members Fyn and Lyn being aberrantly activated in the presence of HPV8-E7. Phospho-proteomics further revealed that E7 not only targets cell polarity and cytoskeletal organization, but also deregulates the phosphorylation status of nuclear proteins involved in DNA damage repair and replication. Many of these differentially phosphorylated proteins turned out to be targets of Fyn and Lyn. Taken together, by using unbiased experimental approaches we have now arrived at a deeper understanding on how fibronectin may affect the signaling cascades in HPV8 positive keratinocytes, which may be key for skin tumorigenesis and that may also aid in the development of novel therapeutic approaches for betaHPV-mediated cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kirschberg, Syed, Dönmez, Heuser, Wilbrand-Hennes, Alonso, Hufbauer and Akgül.)

Human papillomavirus type 159 (HPV159) was identified in an anal swab sample and preliminarily genetically characterized by our group in 2012. Here we present a detailed molecular in silico analysis that showed that the HPV159 viral genome is 7443 bp in length and divided into five early and two late genes, with conserved functional domains and motifs, and a non-coding long control region (LCR) with significant regulatory sequences that allow the virus to complete its life cycle and infect novel host cells. HPV159, clustering into the cutaneotropic Betapapillomavirus ( Beta -PV) genus, is phylogenetically most similar to HPV9, forming an individual phylogenetic group in the viral species Beta -2. After testing a large representative collection of clinical samples with HPV159 type-specific RT-PCR, in addition to the anal canal from which the first HPV159 isolate was obtained, HPV159 was further detected in other muco-cutaneous (4/181, 2.2%), mucosal (22/764, 2.9%), and cutaneous (14/554, 2.5%) clinical samples, suggesting its extensive tissue tropism. However, because very low HPV159 viral loads were estimated in the majority of positive samples, it seemed that HPV159 mainly caused clinically insignificant infections of the skin and mucosa. Using newly developed, highly sensitive HPV159-specific nested PCRs, two additional HPV159 LCR viral variants were identified. Nevertheless, all HPV159 mutations were demonstrated outside important functional domains of the LCR, suggesting that the HPV159 viral variants were most probably not pathogenically different. This complete molecular characterization of HPV159 enhances our knowledge of the genome characteristics, tissue tropism, and phylogenetic diversity of Beta -PVs that infect humans.

Human papillomaviruses (HPVs) of genus betapapillomavirus (betaHPV) are implicated in skin carcinogenesis, but their exact role in keratinocyte transformation is poorly understood. We show an interaction of HPV5 and HPV8 oncoproteins E6 and E7 with the nuclear mitotic apparatus protein 1 (NuMA). Binding of E6 or E7 to NuMA induces little aneuploidy, cell cycle alterations, or aberrant centrosomes. Intracellular localization of NuMA is not altered by E6 and E7 expression in 2D cultures. However, the localization profile is predominantly cytoplasmic in 3D organotypic skin models. Both viral proteins colocalize with NuMA in interphase cells, while only E7 colocalizes with NuMA in mitotic cells. Intriguingly, a small subset of cells shows E7 at only one spindle pole, whereas NuMA is present at both poles. This dissimilar distribution of E7 at the spindle poles may alter cell differentiation, which may in turn be relevant for betaHPV-induced skin carcinogenesis.

Human papillomavirus 8 (HPV8) is associated with the development of squamous cell carcinoma (SCC) of the skin. HPV-infected keratinocytes are able to override normal checkpoint control mechanisms and sustain cell cycle activity, allowing for synthesis of cellular proteins necessary for viral genome amplification. To study how HPV8 may disrupt cell cycle control, we analyzed the impact of HPV8 early gene expression on one of the key regulators of cell cycle and DNA damage response, checkpoint kinase-1 (CHK1). We found that expression of E1, E1̂E4, E2, E6 or E7 individually did not affect CHK1; however, keratinocytes expressing the complete early genome region (CER) of HPV8 showed a profound loss of CHK1 protein levels, that proved to be mediated by E6E7 co-expression. Neither CHK1 promoter regulation nor the ubiquitin-proteasome pathway are involved in HPV8-mediated CHK1 repression. However, CHK1 protein repression in organotypic skin cultures was paralleled by downregulation of the autophagy marker LC3B. Treatment of HPV8-CER expressing cells with the autophagy inhibitor Bafilomycin A1 rescued CHK1 expression and led to LC3B accumulation. Taken together, our data implicate that CHK1 autophagic degradation is enhanced by HPV8, which may contribute to the oncogenic potential of the virus., (© 2019 UICC.)

Background: Recent studies have shown a 13-fold increase of oropharyngeal cancer in the presence of HPV, while α-HPV detection seems to be rare in oral cavity in comparison to anal or cervical district, many novel β and γ types have been isolated in this anatomical site suggesting a wide tropism range. Currently, there are no guidelines recommending HPV oral cavity screening as a mandatory test, and it remains unknown which HPV types should be included in HPV screening programs. Our goal was to assess HPV prevalence in oropharyngeal, anal, and cervical swabs using different sets of primers,which are able to amplify α, β, γ HPV types., Methods: We analysed the presence of HPV DNA in oropharyngeal (n = 124), anal (n = 186), cervical specimens (n = 43) from HIV positive and negative patients using FAP59/64 and MY09/11 primers. All untyped strains were genetically characterized through PCR amplification and direct sequencing of partial L1 region, and the resulting sequences were classified through phylogenetic analysis., Results: HPV prevalence was 20.9% in 124 oropharyngeal swab samples, including infections with multiple HPV types (5.6%). HPV prevalence in this anatomical site was significantly associated with serostatus: 63.3%in HIV positive and 36.3% in HIV negative patients (p < 0.05). Unclassified types were detected in 6 specimens. In our analysis, we did not observe any difference in HPV (α, β, γ) prevalence between men and women. Overall, β species were the most frequently detected 69.7%. When using anal swabs, for HIV positive patients, β genus prevalence was 1% and γ genus was 3.7% including 6 unclassified types. In cervical samples from 43 HIV positive women (18 HPV negative and 25 positive by MY09/11 PCR), only one sample was positivite for β 1 species (2.4%) using FAP primers. Six of the untyped strains clustered with sequences from species 7, 9, 10, 8,12 of γ genus. Four sequences remained unclassified. Finally, β and γ HPV prevalence was significantly lower than their respective HPV prevalence as identified by the Luminex system in all anatomical sites that were analyzed in previous studies., Conclusion: This study provides new information about viral isolates present in oropharyngeal site and it will contribute to improve the monitoring of HPV infection.

Background: Previous investigations studying the association of DNA viruses with salivary gland tumors (SGTs) have led to conflicting results. The aim of this study was to determine the prevalence of different DNA viruses by using a highly sensitive assay in a multi-center series of over 100 fresh frozen salivary gland samples., Methods: DNA was isolated from 84 SGTs (80 parotid tumors and 4 submandibular gland tumors) and 28 normal salivary tissue samples from 85 patients in Northeast Italy. Using a highly sensitive type-specific multiplex genotyping assay, we analyzed the samples for the presence of DNA from 62 different viruses including 47 papillomaviruses, 10 polyomaviruses, and 5 herpesviruses., Results: We observed a high prevalence of beta human papillomavirus DNA in malignant tumors. In contrast, polyomavirus DNA was present in benign, malignant, and non-tumor control samples. Most striking was the significant distribution of herpesvirus DNA in the SGT samples, in particular the high prevalence of Epstein-Barr type 1 and type 2 DNA in Warthin's tumor samples., Conclusion: Our data provides evidence for the presence of DNA viruses in SGTs. Mechanistic studies are needed to further attribute tumor formation to these viruses., (Copyright © 2017. Published by Elsevier Ltd.)

Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease associated with an unusual susceptibility to infections with ubiquitous β-human papillomaviruses (β-HPVs), and in some cases also skin-tropic α genotypes. In this case report, HPV infection patterns were correlated with pathology and clinical manifestations of skin lesions from a patient with EV, without loss-of-function mutations in the EVER genes. HPV infection was investigated by both polymerase chain reaction (PCR) and laser capture microdissection (LCM) PCR, alongside immunofluorescence for the viral proteins E4 and L1. Analysis of eyebrow hair bulbs revealed multiple β-genus HPV infections, including HPV20 and HPV24, which were consistently found in all 11 skin lesions on the patient. Six lesions were also positive for the skin tropic α-genotype, HPV27. Clear-cut differences between two wart-like lesions, one caused by a skin-tropic α-genotype and the other by β-genotypes (as detected by LCM PCR) are shown, including the high cellular proliferation rate in β-HPV-induced lesions. Widespread expression of the early protein E4 was also evident in skin lesions positive for HPV20 by LCM PCR in both tumours and nearby intraepidermal proliferative areas. L1 expression was restricted to areas of intraepidermal proliferation showing productive infection. The patient's inability to control HPV infections is conclusive to the uncontrolled replication of few genotypes from both α and β genera, which cause proliferative lesions with clear-cut clinical and histological features., (© 2014 British Association of Dermatologists.)

Background: Betapapillomaviruses (β-PV) are etiologically associated with epidermodysplasia verruciformis and a proportion of skin precancerous lesions and cancer, mainly in immunocompromised individuals., Objectives: The prevalence and persistence of anal β-PV infection and β-PV type distribution were determined in a cohort of men who have sex with men (MSM). A correlation with HIV-1 infection status and selected demographic and behavioral risk factors were additionally established., Study Design: A total of 181 anal swabs (135 initial and 46 follow-up swabs) obtained from 135 Slovenian MSMs (17.0% HIV-1 positive) were tested for the presence of 25 different β-PV types using Diassay RHA Kit Skin (beta) HPV assay and, if negative, with an in-house nested M(a)/H(a) PCR., Results: β-PVs were detected in 88/135 (65.2%) initial anal swabs. Infection with multiple β-PV types was found in 26 samples; the number of β-PVs ranged from 2 to 9. A total of 29 distinct β-PVs were detected: HPV-36 and HPV-38 were the most prevalent, followed by HPV-23, HPV-24, and HPV-93. HIV-1 positive status, promiscuity and use of alkyl nitrites were significantly associated with a higher prevalence of anal β-PV infection. Three partial DNA sequences suggesting putative new HPV types were identified., Conclusion: To the best of our knowledge, this is the first study to investigate and characterize β-PV infections in the anal region. We showed that anal β-PV infection is highly prevalent in the MSM population and that β-PVs can establish persistent infection in the anal region for up to 4.8 years., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background:  Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples., Methods:  Nasal samples and oral samples were obtained from 312 volunteer Danish healthcare staff (240 women and 72 men), among whom the mean age was 42 years. A total of 311 oral samples and 304 nasal samples were eligible for HPV DNA analysis. HPV types were detected by use of polymerase chain reactions with modified general primers (MGP) and Forslund-Antonsson primers (FAP) and identified by Luminex (for types detected by MGP PCR) or direct sequencing or cloning before sequencing (for types detected by FAP PCR)., Results:  HPV DNA was detected in 6% of the oral samples and 50% of the nasal samples. Seventy-five diverse HPV types or putative HPV types were identified. HPV types within the Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus genera were detected in 3%, 31%, and 23% of the nasal samples, respectively. A putative subtype of HPV76, originally isolated from a feline oral squamous cell carcinoma, was detected in 7 nasal samples., Conclusion:  A large spectrum of HPV types from Betapapillomavirus and Gammapapillomavirus have tropism for the nasal mucosa. The implication of the relatively high prevalence of these viruses in the nasal mucosa is unknown.

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n = 1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20, 23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07-3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27-1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population., (© 2013 UICC.)

Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β7 integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β7-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.

Background: Epidermodysplasia verruciformis Lewandowsky-Lutz (EV) is a rare genodermatosis, characterised by development of numerous verrucous skin lesions caused by specific genotypes of human papillomaviruses belonging to the β-papillomavirus genus. The EV loci were mapped to chromosome 2p21-p24 (EV2) and 17q25 (EV1). On chromosome 17, 2 adjacent related genes--EVER1/TMC6 and EVER2/TMC8--were identified. We reinvestigated 2 patients originally described by Wilhelm Lutz in 1946 with the aim to document the natural course of the disease and confirm his diagnosis., Methods: PCR fragments specific for exons with short flanking intron sequences of EVER1/TMC6 and EVER2/TMC8 genes from patients' DNA were amplified using sequence information. The single-nucleotide polymorphism (SNP) rs7208422 was studied, using restriction fragment length polymorphism analysis., Results: In the index patient, we identified a homozygous TT genotype in exon 8 of the EVER2/TMC8 gene (c.917A→T, p.N306I). The same mutation could thereafter be detected in her sister from paraffin-embedded skin., Conclusion: We have followed one of the first patients described with EV in Basel, Switzerland, in 1930 until today and demonstrated the TT genotype (SNP rs7208422) in the EVER2/TMC8 gene in this index patient and her sister. The results underline the possible relevance of SNP rs7208422 by influencing the susceptibility to β-papillomaviruses and their oncogenic potential., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To investigate the association between genus beta human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population., Design: Population based case-control study., Setting: New Hampshire, USA., Participants: 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus beta human papillomaviruses by multiplex serology., Main Outcome Measures: Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to beta human papillomaviruses., Results: Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual beta human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of beta types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous)=0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55)., Conclusions: These findings support a relation between genus beta human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression.

Background: Human papillomaviruses (HPVs) of the beta genus (beta-PV), especially HPV5 and HPV36, are proposed to play a pathogenic role in psoriasis, but many previous studies have failed to control for potential confounders, including treatment., Objectives: To re-examine the relationship between beta-PV and psoriasis addressing limitations present in previous studies and analyse intra-patient concordance for carriage of HPV., Methods: Plucked eyebrow hairs and forearm skin scrapes were collected from 20 newly diagnosed, previously untreated adult patients with psoriasis and 23 normal controls. A combination of type-specific and degenerate polymerase chain reaction methods was used to achieve comprehensive HPV DNA detection., Results: The prevalence of HPV in hair and skin from psoriasis patients was higher than in controls (83.3% vs. 46.7%, respectively, P < 0.03 corrected for age and clustering). HPV5 or HPV36 were not over-represented. The profile of diverse beta-PV types was comparable in the two groups. Intra-patient concordance for HPV DNA at separate sites was high (P < 0.00001)., Conclusions: Our data do not support a specific causal role for HPV5 or HPV36 in psoriasis, but suggest that psoriatic skin may be more permissive for viral presence than normal skin. High intra-patient concordance for specific HPV types at separate sites, together with the ubiquity of HPV DNA in normal human skin, suggests that an individual becomes colonized with a particular beta-PV profile presumably to the exclusion of other types. To what extent this HPV profile is then causal in the subsequent development of hyperproliferative skin disease is unknown.