Presence of human papillomavirus DNA in voriconazole-associated cutaneous squamous cell carcinoma.

BACKGROUND: Voriconazole and genus beta human papillomavirus (HPV) are independently associated with the development of photo-exposed cutaneous squamous cell carcinoma (SCC) but have not been evaluated concurrently. The objective of this study is to determine the prevalence and type of detectable HPV DNA in voriconazole-associated SCC. METHODS: SCCs from immunosuppressed patients, in those with and without voriconazole exposure, were evaluated by PCR analysis for HPV DNA and compared to SCC from non-immunosuppressed patients. An additional expanded PCR analysis of all SCC that developed in the voriconazole group was also performed. RESULTS: HPV DNA was detected by PCR in all groups regardless of the immunosuppression status (80.5%) with beta HPV most prevalent (64.3-78.6%). However, immunosuppressed patients were significantly more likely to be infected by beta HPV types 5, 8, 14, 20, and 21 (P-value 0.014), and represented the majority of beta HPV types found in the voriconazole group. CONCLUSIONS: In this retrospective study, beta HPV 5, 8, 14, 20, and 21 were commonly detected in voriconazole-associated SCC. The results indicate a possible role of beta HPV in the pathogenesis of cutaneous SCC in photo-exposed areas. Further studies are needed to establish the role of HPV and voriconazole in the pathogenesis of the lesion.

High Ambient Solar UV Correlates with Greater Beta HPV Seropositivity in New South Wales, Australia.

BACKGROUND: Human papillomavirus (HPV) infection is highly prevalent worldwide and may have a role, with sun exposure, in causing cutaneous squamous cell carcinoma. Little is known about the relationship of UV exposure and seroprevalence of cutaneous HPVs in the general population. METHODS: Using multiplex serology, we estimated the seroprevalence of 23 beta and 7 gamma HPVs and 7 other antigens (mu HPV1, HPV63, nu HPV41, alpha HPV16; polyomaviruses HPyV7 and MCV; p53) in a population-based sample of 1,161 Australian 45 and Up Study participants with valid data from blood specimens collected from 2010 to 2012. We calculated prevalence ratios (PR) for the association of each antigen with residential ambient solar UV and other UV-related variables. RESULTS: Seropositivity for at least one beta or gamma HPV was high at 88% (beta HPVs 74%, gamma HPVs 70%), and less in women than men [e.g., PR beta-2 HPV38 = 0.70; 95% confidence interval (CI), 0.56-0.87; any gamma = 0.90; 95% CI, 0.84-0.97]. A high ambient UV level in the 10 years before study enrollment was associated with elevated seroprevalence for genus beta (PRtertile3vs1 any beta = 1.17; 95% CI, 1.07-1.28), and beta-1 to beta-3 species, but not for gamma HPVs. Other UV-related measures had less or no evidence of an association. CONCLUSIONS: Seroprevalence of cutaneous beta HPVs is higher with higher ambient UV exposure in the past 10 years. IMPACT: The observed association between ambient UV in the past 10 years and cutaneous HPVs supports further study of the possible joint role of solar UV and HPV in causing skin cancer.

Prevalence and Epidemiologic Profile of Oral Infection with Alpha, Beta, and Gamma Papillomaviruses in an Asian Chinese Population.

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Characterization of a new genotype of Betapapillomavirus HPV 17 through L1, E7, E7 and LCR sequences.

Human papillomavirus (HPV) exhibits epithelial and mucosal tropism. HPV type 17 belongs to the Betapapillomavirus genus and molecular cloning experiments have identified two subtypes (17a and 17b) isolated from epidermodysplasia verruciformis (EV). HPV subtypes are characterized by dissimilarities from 2 to 10% at the nucleotide level from their referenced HPV. The aim of this study was to characterize the L1, E6, E7 and LCR sequences from an isolate, which was recovered from the oral mucosa of an asymptomatic 63 year-old woman. The whole late gene 1 (L1) was amplified using several sets of primers. The complete early genes 6 and 7 (E6, E7) and the long control region (LCR) were amplified using specific primers. Potential binding sites for transcriptional factors within the LCR were also investigated. Within these sets, the DNA sequence was altered at 91 positions (68 in L1, 13 in E6, 8 in E7, and 2 in LCR sequences). L1 analysis showed high dissimilarity compared with the HPV 17 prototype, reaching 4% of nucleotide substitutions and leading to a probable third 17 subtype. The E6 oncoprotein presented the highest modification among the sequences studied, with four amino acid changes in comparison with the prototype isolate. One amino acid was modified at a position 62 (S-T), a zinc-binding domain (CxxC(C)29 CxxC). Our findings provide data on genetic variations seen in this genotype, reaching to dichotomic branching and pointing to an evolutionary process.

Prevalence and correlates of beta human papillomavirus detection in fingernail samples from mid-adult women.

Cutaneous human papillomaviruses (HPVs) have not been evaluated in fingernails from healthy individuals. To determine prevalence and correlates of ß-HPVs in fingernails from healthy mid-adult women, we tested archived samples collected from 2011 to 2012 using a multiplex PCR combined with Luminex technology for 46 ß-HPV genotypes. One hundred thirteen (61.1%) of 185 fingernail samples were positive for ß-HPV, and the median number of types detected in positive samples was 2 (interquartile range: 1-4). The most common genotypes detected were HPV-23 (ß-2) (13.5%), HPV-38 (ß-2) (13.0%), HPV-5 (ß-1) (9.2%), HPV-107 (ß-2) (8.7%), and HPV-120 (ß-2) (8.7%). In multivariate analysis, ß-HPV detection was associated with age (prevalence ratio [PR] for women 40-51 years versus 30-39 years = 1.30, 95% CI: 1.05-1.62) and race (PR for non-white versus white race = 0.65, 95% CI: 0.45-0.94). The prevalence of ß-HPV in fingernail samples from healthy mid-adult women was similar to the prevalence of ß-HPV reported at other cutaneous sites in prior studies. We did not identify any significant health or sexual behavior predictors of ß-HPV detection in fingernails. Our results support the hypothesis that fingers may serve as a source of transmission or autoinoculation of cutaneous HPVs to other anatomic sites.

Detection of novel Betapapillomaviruses and Gammapapillomaviruses in eyebrow hair follicles using a single-tube 'hanging droplet' PCR assay with modified pan-PV CODEHOP primers.

A modified pan-PV consensus-degenerate hybrid oligonucleotide primer (CODEHOP) PCR was developed for generic and sensitive detection of a broad-spectrum of human papillomaviruses (HPVs) infecting the cutaneous epithelium. To test the analytical sensitivity of the assay we examined 149 eyebrow hair follicle specimens from immunocompetent male patients. HPV DNA was detected in 60 % (89/149) of analysed eyebrow samples with a total of 48 different HPV sequences, representing 21 previously described HPVs and 27 putative novel HPV types. Evidence for ten novel HPV subtypes and seven viral variants, clustering to three out of five genera containing cutaneous HPVs, was also obtained. Thus, we have shown that the modified pan-PV CODEHOP PCR assay is able to identify multiple HPV types, even from different genera, in the same clinical sample. Overall, these results demonstrate that the pan-PV CODEHOP PCR is an excellent tool for screening and identification of novel cutaneous HPVs, even in samples with low viral loads.

Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations.

Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood. We examined the association between seropositivity to cutaneous HPV and 9-valent HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens were tested for antibodies against 9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14 cutaneous types, including ß-types 5/8/12/14/17/22/23/24/38/47, α-type-27, γ-type-4, µ-type-1, and ν-type-41, using a GST L1-based multiplex serology assay. Risk factor data were collected through questionnaires. Logistic regression was used to evaluate associations between mucosal and cutaneous HPV types. Approximately 21% of men were positive for ≥ 1 cutaneous HPV type, and ≥ 1 nine-valent HPV vaccine type at the same time. Men who were seropositive for any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30-2.99), high-risk (AOR = 1.83; 95% CI: 1.04-3.20), low-risk (AOR = 1.92; 95% CI: 1.16-3.18), and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25-3.21). Type-specific cutaneous HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated with seropositivity to 9vHPV, high-risk, and low-risk categories. These data indicate that exposure to cutaneous HPV and 9vHPV types is common. Future longitudinal studies are needed to assess the temporality of these associations.

Concordance of Beta-papillomavirus across anogenital and oral anatomic sites of men: The HIM Study.

We evaluated the concordance between ß-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for agreement. Overall, concordance of ß-HPVs across sites was low and mainly observed among paired genital/anal canal samples. When grouped by species, solely ß-4 HPVs showed moderate concordance in genital/anal pairs (κ = 0.457), which could be attributed to the substantial concordance of HPV-92 in men from Brazil and Mexico (κ > 0.610). ß-HPV type concordance was higher in Mexico, where HPV-19 was consistently concordant in all anatomic site combinations. Our analysis indicates that type-specific concordance across sites is limited to few viral types; however, these infections seem to occur more often than would be expected by chance, suggesting that although rare, there is agreement among sites.

Natural history of human papillomavirus infection of sun-exposed healthy skin of immunocompetent individuals over three climatic seasons and identification of HPV209, a novel betapapillomavirus.

We present the first longitudinal study reporting the natural history of human papillomavirus (HPV) infection in sun-exposed skin of healthy individuals living in a geographical area in which solar UV radiation is influenced by the ozone content of the atmosphere. During three climatic seasons, skin swab samples were obtained from 78 healthy individuals and the prevalence of cutaneous HPVs was assessed with broad-spectrum FAP and CUT primers and determined at 54, 45 and 47 % in spring, summer and winter, respectively. Frequencies of mixed HPV infections were significantly higher in spring with respect to summer and winter (P=0.02). Seventy-one different HPV types/putative types were identified. While 62 volunteers were HPV-infected in at least one season, 23 had persistent infections. ß-PVs (ß-1) were the most prevalent and persistent. Age was associated with both the infection status (P=0.01) and the type of HPV infection (no infection, indeterminate/transient, persistent P=0.02). The molecular/phylogenetic analysis of the newly identified ß-PV, officially designated as HPV209, showed that the virus has a typical genomic organization of cutaneous HPVs with five early (E6, E7, E1, E2 and E4) and two late genes (L2 and L1), which clusters to the species ß-2. This provides useful data on cutaneous HPV infections in high UV-exposed regions.

Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

INTRODUCTION: The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. METHODS: A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. CONCLUSION: Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

Beta-HPV types in patients with head and neck pathology and in healthy subjects.

BACKGROUND: Human papillomaviruses (HPV) are a heterogeneous group of viruses classified into five genera. The beta-HPV type (beta-PV) infection is very common but mostly asymptomatic in immunocompetent individuals. However, beta-PVs play a role in Epidermodysplasia verruciformis and possibly in non-melanoma skin cancer. Head and neck cancer (HNC) is a common cancer type worldwide and high-risk alpha-PV involvement in HNC has been extensively studied but beta-PV types have rarely been the focus of such studies. OBJECTIVES: To evaluate the prevalence of beta-PV types in HNC, subjects with non-malignant or potentially pre-malignant oral lesions, and healthy controls. STUDY DESIGN: The frequency of different beta-PVs in samples from oral (n=35) and oropharyngeal (n=35) cancer patients, gender- and age-matched healthy controls (n=70), and subjects with various non-malignant or potentially pre-malignant oral lesions (n=102) was assessed by a highly sensitive, bead-based, multiplex genotyping assay. RESULTS: Overall, 54.8% of all tested samples contained at least one beta-PV type. Even though the correlation between types found in lavage and tissue specimens from cancer patients was low, there was a large statistically significant difference between oropharyngeal cancer patients and matched controls for HPV5 (P=0.003; OR=15.58) and between both oral (P=0.026; OR=5.7) and oropharyngeal cancer patients (P=0.002; OR=25.5) and controls for HPV122. In addition, there was no correlation between the prevalence of alpha and beta-PVs in the study patients. CONCLUSION: The study provides new data on the prevalence of beta-PVs in HNC. HPV5 was found significantly associated with HNC as already observed by other studies. Additionally, the significant association of HPV122 with HNC might warrant further study as this type has not been extensively studied so far.

Human papillomavirus infection and p16 expression in the immunocompetent patients with extragenital/extraungual Bowen's disease.

BACKGROUND: The role of human papillomaviruses (HPV) in the development of squamous cell carcinoma (SCC) has been established for anogenital lesions but still remains controversial for carcinomas in other sites. The aim of this study was to determine the α-HPV and ß-HPV prevalence and their association with p16 expression, sun exposure, and clinicopathological findings in patients with Bowen's disease (BD). METHODS: One hundred sixty nine skin biopsy specimens from 157 immunocompetent patients with extragenital/extraungual BD were examined for HPV status and p16 expression. The presence of koilocyte-like changes, solar elastosis and papillomatosis was recorded for each specimen. RESULTS: BD was diagnosed more often in potentially sun-exposed sites with prevalence 73.6 % and a remarkable predilection for the head and neck region. High risk α-HPV or ß-HPV were detected in 34.7 % of lesions and ß-HPV infections dominated over α-HPV. Higher prevalence of koilocyte-like changes and papillomatosis was found in HPV-positive specimens but it was not statistically significant. The expression of p16 was detected in 79.8 % of lesions and displayed no correlation with the HPV status. HPV-positivity tended to be detected more often in sun-protected sites. Dual infections by α-HPV/ß-HPV genera and mixed α-HPV infections were not detected, while 37.5 % of ß-HPV positive specimens were infected by two or more ß-HPV genotypes. HPV 9 was significantly associated with mixed ß-HPV infections. CONCLUSIONS: HPV may play an etiological role at least in some SCC in situ arising in extragenital sites. Sunprotected sites may be more dependent on HPV-mediated co-carcinogenesis than sun exposed areas. The presence of the p16-expression, papillomatosis or koilocyte-like change is not a reliable marker of HPV infection in SCC in situ.

Association Between ß-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals-A Meta-analysis.

Importance: Existing epidemiological evidence remains controversial regarding the association between ß-genus human papillomavirus (ß-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals. Objective: We aimed to clarify this association and evaluate type-specific ß-HPV involvement. Data Sources: We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: "human papillomavirus" and "cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms." Study Selection: Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific ß-HPV. Data Extraction and Synthesis: We first assessed the heterogeneity among study-specific ORs using the Q statistic and I2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot-based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. Main Outcomes and Measures: Pooled ORs and 95% CIs for overall ß-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. Results: Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between ß-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall ß-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development. Conclusions and Relevance: This study serves as added evidence supporting ß-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts.

Betapapillomavirus in multiple non-melanoma skin cancers of Netherton syndrome: Case report and published work review.

Netherton syndrome (NS) is a rare genetic disease presenting with ichthyosiform erythroderma, hair alterations and atopy. NS is due to SPINK5 gene mutations, which cause absent or decreased expression of the encoded protein lymphoepithelial Kazal-type-related inhibitor (LEKTI) in all stratified epithelia. We report a 43-year-old man affected with NS, who developed several squamous and basal cell carcinomas on the face, ears and scalp and papillomatous lesions of hips, groin and genitoanal area. Molecular analysis of the SPINK5 gene revealed homozygosity for the recurrent mutation c.238dupG. Human papillomavirus (HPV) DNA detection and genotyping on patient skin carcinomas and hyperplastic lesions found betapapillomavirus DNA in 10 of 12 (83%) carcinomas and in a hip papilloma, with multiple betapapillomavirus types being identified. Immunohistochemistry showed upregulated expression of p16(INK4a) protein in nine of 12 (75%) patient carcinomas, in line with findings reported in HPV-related cancers. LEKTI and filaggrin immunostaining was strongly decreased in patient skin. A published work search for NS cases with skin cancers and HPV infection identified 15 NS patients, five of them showing mucosal or cutaneous HPV infection. Overall, our results confirm the increased susceptibility to skin carcinomas of some NS patients and provide further evidence of an association between HPV and non-melanoma skin cancers in NS. The highly impaired skin barrier function, hallmark of NS, could facilitate HPV infection, in turn increasing the risk for cancer development.

A large spectrum of alpha and beta papillomaviruses are detected in human stool samples.

Human papillomaviruses (HPVs) have been detected in urban wastewaters, demonstrating that epitheliotropic viruses can find their way into sewage through the washing of skin and mucous membranes. Papillomavirus shedding through faeces is still an unexplored issue. The objective of the present study was to investigate the presence of HPVs in stool samples. We analysed 103 faecal specimens collected from hospitalized patients with diarrhoea using validated primers able to detect α, ß and γ HPVs. PCR products underwent sequencing analysis and sequences were aligned to reference genomes from the Papillomavirus Episteme database. A total of 15 sequences were characterized from the faecal samples. Thirteen samples (12.6 %) were positive for nine genotypes belonging to the α and ß genera: HPV32 (LR, α1), HPV39 (HR, α7), HPV44 (LR, α10), HPV8 (ß1), HPV9, HPV23, HPV37, HPV38 and HPV120 (ß2). Two putative novel genotypes of the ß genus, species 1 and 2, were also detected. The tissue(s) of origin is unknown, since faeces can collect HPVs originating from or passing through the entire digestive system. To our knowledge, this is the first investigation on the occurrence and diversity of HPVs in faecal samples. Results from this study demonstrate that HPVs can find their way into sewage as a consequence of shedding in the faeces. This highlights the need for further studies aimed at understanding the prevalence of HPV in different water environments and the potential for waterborne transmission.

Frequency of Betapapillomavirus infections among HIV infected and uninfected Black Zimbabweans with cutaneous lesions.

Human papillomavirus (HPV) types from the Betapapillomavirus (ß-HPV) genus are plentiful in non-melanoma skin cancers and warts among Caucasians, but there is paucity of information among black Africans. To determine the frequency of ß-HPV genotypes in cutaneous infections among Black Zimbabweans, a cross-sectional study was carried out in which blood samples and skin biopsies were collected from patients infected and uninfected with HIV attending a referral hospital. We included 144 participants (72 infected and 72 uninfected with HIV) with clinically apparent cutaneous warts (n = 34), suspected non-melanoma skin cancers (n = 98) and Kaposi sarcoma (KS) (n = 18). The skin biopsies were analyzed for HPV DNA presence and type. ß-HPV DNA was identified among 70% (101/144) and was significantly higher among patients infected with HIV, 79% (57/72) compared to the HIV uninfected 61% (44/72) [OR = 2.42, 95% CI (1.09-5.47), P = 0.018]. All patients with warts, 89% of those with KS and 58% of those with non-melanoma skin cancers were HPV DNA positive and ß-HPV type 14 was identified in nearly half of the study participants 49.3% (71/144). Single HPV infections were observed in 33.7% (34/101) of the participants that were HPV DNA positive, 66.3% (67/101) had multiple HPV types. There was no significant difference between patients infected and uninfected with HIV in terms of multiple HPV infections. The distribution of different HPV types did not reveal any association with age and gender but there was an association between HPV 14 and HIV immune status. ß-HPVs are not uncommon among the Black Zimbabweans with skin lesions.

Persistent toenail onycholysis associated with Beta-papillomavirus infection of the nail bed.

Onycholysis, separation of the nail plate from the nail bed, is etiologically classified as primary (idiopathic) or secondary (eg, caused by psoriasis, squamous cell carcinoma). Repetitive microtrauma plays a role in idiopathic onycholysis and also facilitates human papillomavirus (HPV) infection. Herein, we report a case of persistent primary onycholysis associated with repetitive trauma and infection by a multiplicity of Beta-papillomavirus (Beta-PV) genotypes. An otherwise healthy 27-year-old woman presented with a 6-year history of onycholysis of the halluces and right second toe. Her occupation required wearing steel-toed boots. Fungal cultures were negative and antifungal therapy was ineffective. Punch biopsy of the hallux nail bed revealed epidermal hyperplasia, acanthosis, hypergranulosis, hyperkeratosis, and regions of koilocytosis without significant inflammation. This histopathology implicated chronic irritation and HPV infection. Immunohistochemistry demonstrated productive HPV infection. Nested PCR using degenerate consensus primers revealed infection with 5 known and 1 novel Beta-PV genotypes (HPV 5, HPV 8, HPV 20, HPV 23, HPV 37, and FA25). The histopathology of primary onycholysis is unknown. Based on the aforementioned, we propose that repetitive microtrauma caused by wearing steel-toed boots promoted onycholysis and HPV infection, the latter of which, altered the differentiation of nail bed epithelium, preventing adhesion of nail plate to the nail bed. Lastly, the presence of oncogenic Beta-PV genotypes (ie, HPV 5, 8, and 20) implicates a risk for subungual squamous cell carcinoma, particularly if the nail remains symptomatic and persistently irritated.

Betapapillomaviruses in the anal canal of HIV positive and HIV negative men who have sex with men.

BACKGROUND: Betapapillomaviruses (ß-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 ß-PV infection and ß-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 ß-PV types using Diassay RHA Kit Skin (beta) HPV assay and, if negative, with an in-house nested M(a)/H(a) PCR. RESULTS: ß-PVs were detected in 88/135 (65.2%) initial anal swabs. Infection with multiple ß-PV types was found in 26 samples; the number of ß-PVs ranged from 2 to 9. A total of 29 distinct ß-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 ß-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 ß-PV infections in the anal region. We showed that anal ß-PV infection is highly prevalent in the MSM population and that ß-PVs can establish persistent infection in the anal region for up to 4.8 years.

Analysis of human ß-papillomavirus and Merkel cell polyomavirus infection in skin lesions and eyebrow hair bulbs from a cohort of patients with chronic lymphocytic leukaemia.

BACKGROUND: Research demonstrates an increased incidence of skin cancer in immunocompromised hosts, including patients with chronic lymphocytic leukaemia (CLL) and organ transplant recipients (OTRs). Active human ß-papillomavirus (ß-HPV) infection has been found in OTR skin lesions, suggesting its possible involvement in skin carcinogenesis. Merkel cell polyomavirus (MCPyV) has also been reported in cases of skin cancer. OBJECTIVES: To investigate the potential correlations between patient clinical features and skin cancer development, and the presence of ß-HPV and MCPyV DNA and protein markers in skin lesions and hair bulbs from patients with CLL. METHODS: The clinical features of 293 patients with CLL were analysed according to the presence or absence of skin lesions. ß-HPV and MCPyV infection was investigated in skin lesions and hair bulbs from the study cohort by both polymerase chain reaction (PCR) analysis and immunohistochemical screening. RESULTS: No significant correlations were observed between any of the analysed haematological parameters and the development of skin cancer. PCR analysis revealed the presence of ß-HPV and MCPyV DNA in skin lesions, and 83% of positivity for MCPyV DNA in hair bulbs, while systematic immunohistochemical analysis of all the lesions failed to detect any expression of the viral proteins ß-HPV E4, L1 or MCPyV LTAg. CONCLUSIONS: Overall, the data indicate that carriage of ß-HPV and MCPyV in the lesional skin and hair bulbs from patients with CLL without any evident reactivation at skin tumour sites most likely represents coincidental rather than causal infection. This contrasts with previous findings in relation to OTR-derived skin lesions.