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Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its similarity to nail malignant melanoma, particularly with respect to the clinical manifestation of black nail streaks. While skin biopsy is usually employed for diagnosis, it is an invasive procedure. We report the case of a 52-year-old healthy Japanese male with a pigmented streak on the nail of the fourth finger of his right hand, which had extended from the central to the lateral nail fold within 4 months. Dermoscopic examination revealed a dark-brown pigmented band with splinter microhemorrhage. Clinically, nail Bowen's disease was suspected. The lesion was excised in strips under local anesthesia. Histopathological examination revealed hyperkeratosis, parakeratosis, papillomatosis, and dyskeratotic cells with atypical nuclei irregularly arranged. Immunohistochemistry using anti-HPV L1 antibody detected HPV-positive cells in the upper epidermis and stratum corneum of the nail matrix. Mucosal high-risk HPV type 58 DNA was detected from brush cytology of the keratotic surface prior to surgery, which was confirmed in formalin-fixed, paraffin-embedded excised samples using polymerase chain reaction (PCR) and subsequent direct DNA sequencing. Our case highlights HPV type 58 as a potential causative agent of nail Bowen's disease and shows that brush cytology of the surface material prior to excision may be a useful and less invasive way for mucosal high-risk HPV detection. PCR analysis of the nail surface could serve as a supplementary diagnostic tool for nail Bowen's disease., (© 2024 Japanese Dermatological Association.)

Mohs micrographic surgery is the gold standard for treating many types of skin cancer, particularly skin cancers of high-risk areas such as the face, genitalia, and digits, due to its tissue-sparing technique and low recurrence rates. The use of Mohs micrographic surgery for human papilloma virus-associated cutaneous malignancies has yet to be explored in a systematic review. The authors sought to assess outcomes including recurrence rates of Mohs micrographic surgery for human papilloma virus-associated cutaneous malignancies. PubMed was searched for the use of Mohs micrographic surgery in types of human papilloma virus-associated cutaneous malignancies. After application of exclusion and inclusion criteria, 33 articles were included. 700 cases from 33 studies were included. Overall recurrence rate following Mohs micrographic surgery was 39/478 (8.2%) at a mean follow-up time of 51.5 months. Recurrence rate for nail unit/digit squamous cell carcinoma was 10/103 (9.7%) at mean follow-up of 47.6 months. Recurrence rate for penile squamous cell carcinoma was 15/181 (8.3%) at mean follow-up of 45.9 months. Recurrence rate for Bowen's disease in extragenital areas was 11/189 (5.9%) at mean follow-up of 59.7 months. Patients overall reported satisfactory functional and cosmetic results. Mohs micrographic surgery demonstrates low recurrence rates and excellent functional and cosmetic outcomes in the treatment of human papilloma virus-associated cutaneous malignancies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood., Objectives: To investigate the differences in HPV detection rates in BD samples across various body regions and analyse the expression patterns of p53, p16 and Ki-67 in relation to HPV presence., Methods: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53 and Ki-67 was performed., Results: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (9/13, 69%, P < 0.001) and digital (5/10, 50%, P = 0.02) areas compared with those in the other regions. HPV presence was significantly correlated with p53 negativity (P = 0.002), the p53 'non-overexpression' IHC pattern (P < 0.001) and p16-p53 immunostain pattern discordance (P < 0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern or Ki-67 expression., Conclusions: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in the pathogenesis of BD in pelvic and digital regions., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Human papillomavirus (HPV) is a common sexually transmitted infection with wide-ranging clinical manifestations. High-risk anogenital HPV genotypes have also been reported to cause extragenital disease. We describe the case of a 69-year-old male patient living with HIV who was diagnosed with HPV-16 associated Bowen's Disease (BD) of the right middle finger nailbed, despite good virologic control and immune reconstitution. The lesion was managed surgically with adjunctive post-exposure HPV vaccination. This case adds to the growing body of evidence of extra-genital HPV disease attributable to anogenital genotypes in people living with HIV., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A clinical case that demonstrates the development of human papilloma virus (HPV)-associated penile intraepithelial neoplasia (PIN), namely the erythematous form of bowenoid papulosis in a young patient, as well as a delay in making a correct diagnosis due to incorrect diagnostic tactics and low alertness of doctors regarding oncologic diseases, is presented in the article. Penile intraepithelial neoplasia is the histological term for precancerous lesions of the penis. Timeliness is important in the diagnosis of PIN, since currently there is a high morbidity and mortality associated with the progression to squamous cell penile carcinoma. From the morphologic and pathogenetic standpoints, HPV-negative (differentiated) and HPV-positive subtypes of PIN are divided. The latter includes Bowenoid papulosis, erythroplasia of Queyrat and Bowen's disease. It is important to carry out a differential diagnosis between these lesions, since the rate of development of penile cancer for erythroplasia of Queyrat is 30%, for Bowen's disease is 5% and for bowenoid papulosis is 1%.

Background: The detection rate of human papillomavirus (HPV) in Bowen's disease (BD) varies greatly., Objectives: To detect HPV DNA in BD samples using next-generation sequencing (NGS) and compare HPV detection rates between pelvic and non-pelvic BD., Materials and Methods: We evaluated 99 patients with BD in our institution. DNA was extracted from formalin-fixed and paraffin embedded (FFPE) tissue blocks. The presence of HPV DNA material was detected using special kit-based NGS technology. Clinical characteristics and HPV detection rates were then compared between pelvic and non-pelvic BD samples., Results: HPV was detected in 26 (26.3%) BD samples. A total of 10 types of α-HPV was detected: HPV 16, 53, 31, 58, 66, 26, 27, 57, 45, and 72. The most common HPV type was 16 (12.1%). Only two types (27 and 57) were frequently classified as cutaneous type, and the rest were mucosal types. The HPV detection rate was significantly higher in pelvic BD (45.2%) compared to non-pelvic BD (17.6%)., Conclusion: The present study suggests that sexually transmitted mucosal α-HPV plays a significant role in the pathogenesis of BD, especially in the pelvic region.

Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV-58 is classified as a high-risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV-58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV-58-associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33-year-old man presented with multiple reddish-brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin-embedded samples and identified HPV-58 sublineage A1. Additionally, we review previous reports on HPV-58-associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV-58 lineages and carcinogenesis in the skin., (© 2018 Japanese Dermatological Association.)

Squamous cell carcinoma in situ, also known as Bowen's disease (BD), is a skin malignancy most commonly seen in middle-aged and elderly adults. Pediatric BD is rare and can be a diagnostic challenge for physicians. Digital BD has largely been associated with human papilloma virus. We report an immunocompetent 11-year-old girl with periungual pigmented BD induced by high-risk human papilloma virus., (© 2018 Wiley Periodicals, Inc.)

Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity., Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.

Bowenoid in situ carcinomas (BISCs) are papillomavirus (PV)-induced skin neoplasms that are thought to be caused by Felis catus papillomavirus (FcaPV) 2. As BISCs are typically multiple and can become extensive, they can be difficult to treat. Herein we describe 4 cats that developed skin neoplasms that contained FcaPV-3 DNA. One cat developed multiple basal cell carcinomas (BCCs), 1 a BISC with unusual extension into hair follicles, and 2 developed a single typical-appearing BISC. All neoplasms contained prominent PV-induced cell changes and intense p16 CDKN2a protein immunostaining. Results from these 4 cats provide evidence that FcaPV-3 could cause a proportion of feline skin cancers, albeit less frequently than FcaPV-2. Excision of the typical BISCs and the BCCs appeared curative. Although the cat with the unusual BISC was euthanized because of the large size of the lesion, evidence from these 4 cats suggests that skin neoplasms that contain FcaPV-3 DNA may have a less aggressive clinical behavior than those associated with FcaPV-2. A consistent feature of the neoplasms in all 4 cats was the presence of prominent basophilic intracytoplasmic inclusion bodies; these inclusions have not been reported in lesions caused by FcaPV-2, to our knowledge, and their detection may allow differentiation between the different PV types and could therefore be a useful prognostic feature.

An increased rate of second nonmelanoma skin cancers is found in immunocompromised patients. Epidemiological and molecular data implicate ultraviolet radiation as the major risk factor. In addition, there is increasing evidence supporting the role of human papillomavirus (HPV) in the pathogenesis of premalignant and malignant skin lesions in both immunocompetent and immunocompromised patients. In a retrospective cross-sectional study, the authors examined the expression of p16 by immunohistochemistry and the presence of mucosal (α-genus) and cutaneous/epidermodysplasia verruciformis (β-genus) HPV DNA by polymerase chain reaction in 29 biopsy specimens of extragenital/extraungual Bowen disease (BD) from 24 Eastern European white immunocompromised patients. Furthermore, the author evaluated the association between the expression of p16 protein and the presence of HPV DNA. Among 25 specimens from 21 patients evaluable by polymerase chain reaction, HPV DNA was detected in 10 (40%) BD lesions from 9 patients. Beta-HPV predominated over alpha-HPV types. Among 29 immunohistochemically evaluable BD specimens, 22 lesions (∼76%) from 20 patients were scored as p16 positive. HPV DNA-positive and HPV DNA-negative lesions displayed the same proportion of p16 positivity (80%) and no correlation was found between the HPV DNA presence and the p16 expression status. Our pilot study demonstrated that β-HPV infections predominate in BD cases diagnosed among immunocompromised patients, although high- and low-risk mucosal (alpha) HPV genotypes may be detected in a minority of cases. In contrast to anogenital HPV-associated lesions, positive p16 expression is not a reliable marker of high-risk α-HPV infection in BD cases, as it can be also detected in β-HPV infected and HPV-negative cases.

Background: Bowen disease is the most frequent nail malignancy, usually seen as a verrucous plaque of the nail in men., Objective: To characterize the affected patient population, the clinical manifestations, the diagnostic delay and diagnostic steps, and presence of human papilloma virus (HPV) infection., Methods: We retrospectively evaluated all cases of Bowen disease of the nail unit over a period of 9 years. Data were obtained from our electronic database. Human papilloma virus genotype was assessed in biopsy specimens by polymerase chain reaction (PCR) sequencing., Results: We identified 12 cases of Bowen disease of the nail unit in 10 patients. Mean age at onset was 52 years, with a male predominance of 90%. The thumb and middle finger were the most frequently affected (66%). Fifty percent of the lesions presented as periungual and subungual verrucous tumours. Patients sought medical evaluation after a mean delay of 5.7 years; histopathological diagnosis was made after a mean delay of 3.2 years. HPV infection was identified in 75% of the cases., Conclusions: Any recently appeared verrucous lesion of the nail unit in men above the age of 40 years should raise the suspicion of Bowen disease and lead to further histopathological diagnostic procedures., (© 2016 European Academy of Dermatology and Venereology.)

Background: Some examples of Bowen disease lack the characteristic broad parakeratosis making their histopathologic diagnosis particularly difficult in small and incomplete biopsies., Materials and Methods: The archives of our dermatopathology laboratory were searched for cases of Bowen disease with >75% orthokeratosis (orthokeratotic Bowen disease) and classic Bowen disease (>25% parakeratosis). Selected specimens were evaluated histopathologically, using immunohistochemical stains (CK10, CK7, Bcl-2, p16 and Ki-67) and by DNA amplification/sequencing for human papilloma virus (HPV) subtypes., Results: Among 102 consecutive samples 14 cases of orthokeratotic Bowen disease were identified. In comparison with 24 examples of classic Bowen disease, the orthokeratotic examples occurred more frequently in female and younger patients (p = 0.04 and 0.008, respectively) but shared most of the histopathologic features of classic Bowen disease except a preserved granular layer and relative absence of the eyeliner sign (p < 0.0001 and p = 0.042, respectively). Immunohistochemical staining patterns were similar between the two groups. HPV types 11, 16 and 58 were identified from five cases of orthokeratotic Bowen disease., Conclusion: Orthokeratotic Bowen disease is a distinct variant of squamous cell carcinoma in situ associated with HPV infection in less than half of the cases studied., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The bowenoid transformation of seborrheic keratosis (SK) has rarely been reported. The purpose of this study is to identify their diagnostic immunohistochemical features and association with human papillomavirus (HPV) infection. Skin biopsy specimens of the phenomenon were retrieved from 2001 to 2010. Benign SK, Bowen disease, bowenoid papulosis, and squamous cell carcinoma were included as controls. All specimens were stained for hematoxylin and eosin, Ki-67, p21, p16, p53, and cyclin D1. Polymerase chain reaction-amplified HPV DNA was analyzed. Seventeen cases of SK with bowenoid transformation were identified. The immunohistochemical pattern of bowenoid transformation was similar to that of Bowen disease and bowenoid papulosis. The malignant cells exhibited increased expressions of p16, p21, and ki-67 and a decreased expression of cyclin D1 (P < 0.01). HPV DNA was detected in 5 cases of bowenoid transformation. In conclusion, a portion of the cases of SK with bowenoid transformation were associated with HPV infection. Selective immunohistochemical stains were helpful in the diagnosis of malignant change in these cases.

We report the clinical and pathological findings of two cases of Bowen's disease (BD) with features resembling myrmecia wart, and tried to find evidence of human papillomavirus (HPV) infection in such lesions by immunohistological staining, genotyping systems, polymerase chain reaction (PCR) and electron microscopy. Both cases manifested unique barnacle-like hyperkeratotic nodules or plaques clinically, and microscopically proliferation of atypical keratinocytes involving the entire thickness of the epidermis, hypergranulosis with eosinophilic and/or basophilic inclusion bodies, features that mimicked myrmecia wart. Electron microscopy revealed myrmecia inclusion-like large intranuclear and cytoplasmic electron-dense bodies. Immunohistological staining with anti-HPV antibody, genotyping systems for HPV infection and specific PCR designed to detect HPV-1 L1 sequences failed to detect evidence of HPV infection. P16(INK4a) was overexpressed in the atypical keratinocytes of both cases. This finding suggests that the pathogenesis of these two BD may involve certain unknown or undetectable HPV, or reflect disturbances of the Rb signaling pathway unrelated to HPV infection. The unique "myrmecioid" clinicopathological features in our cases suggest that this type of lesion may be a new variant of BD., (© 2014 Japanese Dermatological Association.)

Genital Bowen disease (BD) has been linked to the high-risk types of human papillomavirus (HPV) infection. Recently, it has been recognized that HPV also can be associated with extragenital BD. HPV oncoproteins E6 and E7 interfere with the function of p53 and pRb, respectively, leading carcinogenesis. p16(INK4a) overexpression induced by inactivation of pRb is recognized as a surrogate marker for HPV-associated cervical cancer. In this study, we examined the presence of HPV DNA in 142 BD lesions by polymerase chain reaction (PCR), and determined the type of HPV by PCR restriction fragment length polymorphism or direct DNA sequencing. HPV DNA was detected in 66.7% of genital BD and 8.3% of extragenital BD. The types of HPV detected were HPV types 6, 16, 33, 52, 56, 58 and 59. We also investigated the expression of p16(INK4a) , pRb and p53 by immunohistochemistry. Positive expression was detected in 88.6% for p16(INK4a) , 25.2% for pRb, and 63.8% for p53. There was no significant difference in p16(INK4a) and pRb expression between HPV-positive and -negative BD. However, a strong correlation of HPV positivity with p53 negativity was found. A total of 66.7% of HPV-positive BD showed no p53 expression, whereas the corresponding rate was 32.8% of HPV-negative BD. This study demonstrated that HPV can participate in the development of BD, not only in the genital lesion, but also in extragenital lesion. p16(INK) (4a) overexpression is not a marker for HPV infection in BD. Instead, negative p53 expression is correlated with HPV-associated BD., (© 2014 Japanese Dermatological Association.)

There is increasing evidence that papillomaviruses (PVs) may cause skin cancer in cats. Neoplasms most frequently contain Felis domesticus PV type 2 (FdPV-2) DNA, but other PV DNA sequences have also been detected suggesting multiple PVs could cause disease. One of these sequences, FdPV-MY2, was previously detected in 5 of a series of 70 feline skin cancers. The aim was to determine the genome sequence of this PV. Using the circular nature of PV DNA, 'outward facing' primers specific for FdPV-MY2 were designed and amplified a 7300 bp length of DNA from a feline Bowenoid in situ carcinoma (BISC) that showed microscopic evidence of a viral etiology and tested positive for FdPV-MY2 DNA. The PCR product was sequenced using next generation sequencing technology. The full genomic sequence of the virus, comprising 7583 bp, was assembled and analyzed. As this is the third PV from a domestic cat, the virus was designated Felis catus PV type 3 (FcaPV-3). Consistent with other PVs, the putative coding regions of FcaPV-3 were predicted to produce 6 early proteins and 2 late ones. Classification was difficult as the virus contained over 60% nucleotide similarity within the ORF L1 with PVs from 3 different genera. However, based on phylogenetic analysis of ORF L1, FcaPV-3 was most closely related to the tau-PVs CPV-2 and CPV-7. As FcaPV-3 has over 60% nucleotide similarity with the ORF L1 of both tau-PVs, it is proposed that FcaPV-3 is classified in the genus Taupapillomavirus and is the first non-canine PV in this genus., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Human papillomavirus (HPV) is a well-known risk factor for many human cancers, especially cervical cancers. Among the nonmelanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has also been shown to be closely associated with the high-risk types of HPV, especially HPV16. We report a case of BD of the palm, which is a very rare location for BD. In addition to its rare location, HPV52, which is classified as a mucous high-risk HPV type, was detected in the lesion by PCR restriction fragment length polymorphism analysis. To our knowledge, this is the first reported case of BD associated with HPV52., (© 2013 British Association of Dermatologists.)

Human papillomavirus (HPV) incorporates high-risk HPV (hrHPV) and low-risk HPV (lrHPV) subtypes according to its contribution to oncogenesis. Different HPV subtypes could regulate the cell cycle of infected cells at different levels. To date, the expression of cyclin D1 and cyclin E in Bowenoid papulosis (BP) tissues and its association with HPV infection still remains elusive. In the present study, genotyping was performed to identify the HPV subtypes in 44 BP specimens. In addition, immunohistochemistry was performed to detect the expression of cell cycle related proteins cyclin D1 and cyclin E in BP tissues as well as normal tissues. We found that there were 20 patients with hrHPV subtypes, 6 patients with lrHPV subtypes, and 18 patients with combined high and low (hr/lr) HPV subtypes. Cyclin D1 expression in patients with hrHPV subtypes (P=0.0408), in patients with lrHPV subtypes (P=0.0002) and in patients with hr/lr HPV subtypes (P=0.0047) was significantly higher than that in normal controls, respectively. Cyclin D1 expression in patients with hr/lr HPV subtypes (P<0.0001) and in patients with lrHPV subtypes (P=0.0244) was significantly higher than that in patients with hrHPV subtypes, respectively. Cyclin E expression in patients with hrHPV subtypes (P<0.0001), in patients with lrHPV subtypes (P=0.0005), and in patients with hr/lr HPV subtypes (P<0.0001) was significantly higher than that in normal controls, respectively. Cyclin E expression in patients with hrHPV subtypes was significantly higher than that in patients with lrHPV subtypes (P=0.0032). Our data suggest that HPV infection is strongly associated with the pathogenesis of BP, and further support the notion that HPV may be involved in the regulation of the expression of cell cycle related proteins, cyclin D1 and cyclin E, in the pathogenesis of BP., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Human papillomavirus (HPV) infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (n = 30), squamous cell carcinoma (n = 11), bowenoid papulosis (n = 9), verrucous carcinoma (n = 1), actinic keratosis (n = 5), and basal cell carcinoma (n = 5). We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease (n = 5) nor those with squamous cell carcinoma (n = 3) showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6%) of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (n = 3), while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7%) of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.

In the present study, we aim to evaluate the application potential of a combined assay of human telomerase reverse transcriptase (hTERT) and E6 oncoprotein in screening the virus-infected keratinocytes with higher telomerase activity in human papillomaviruses (HPV) 16- and 18-related bowenoid papulosis (BP). HPV16/18 DNA in BP (n = 123) was identified by in situ hybridization, the expression of hTERT and E6 in HPV16/18-related BP (n = 68) was determined by immunohistochemistry. We demonstrated that the expression of hTERT correlated well with that of E6 oncoprotein in HPV16/18-related BP lesions (Spearman rho = 0.868, P < 0.01). Furthermore, the majority of keratinocytes with positive nuclear staining for hTERT or E6 in the consecutive sections of each HPV16/18-related BP lesion showed nuclear paleomorphism or nuclear mitosis. In conclusion, we suggested that a combined assay of hTERT and E6 oncoprotein can be used to screen the HPV-infected keratinocytes with higher telomerase activity in HPV16-related and HPV18-related BP lesions.

Epidermodysplasia verruciformis (EV) is a rare heritable skin disease that results in unusual susceptibility to infection with specific types of human papillomavirus (HPV). Here we report a 53-year-old man with EV who developed Bowen's disease on his lower eyelid and the chest. Mutation analysis of EVER1 gene revealed homozygous splice acceptor site mutation (IVS8-2, A > T). In this patient, HPV3, HPV14, and HPV38 had been identified from the skin lesions. The Bowen's skin lesion on the left lower eye-lid was treated by photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and pulsed dye laser (PDL). After two rounds of the PDT treatment, the skin lesion disappeared and a skin biopsy confirmed the efficacy of the treatment. This method was simple, less invasive than other treatments, and achieved a satisfactory cosmetic result.

Background: Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear., Objective: To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations., Methods: Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease., Results: Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types., Conclusions: This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Human papillomavirus (HPV) is known to cause cervical cancer. Because it has been detected in lesions of Bowenoid papulosis, Bowen's disease, and Bowen's carcinoma, HPV infection has been implicated in the pathogenesis of these diseases., Methods: A 44-year-old man was diagnosed clinicopathologically with Bowen's carcinoma of the right great toe. He developed multiple organ metastases and died. We examined HPV DNA in skin biopsy specimens from the primary and skin metastatic lesions by polymerase chain reaction (PCR) and in situ hybridization (ISH). The PCR assay was carried out using primer sets specifically designed for detecting the E6 and E7 genes of the HPV types associated with malignancy. Purified and cloned PCR products were subjected to DNA sequence analysis. The ISH studies used INFORM(®) HPV III probes., Results: We found HPV DNA in specimens from both the primary and the skin metastatic lesions. DNA sequencing detected HPV type 16. We compared the base sequences of viral DNA from the primary and metastatic lesions. Point mutations of the base sequences of the E6 and E7 genes were observed in viral DNA from metastases but not in that from primary lesions. The E6 gene had mutated from G to A in the 383rd base sequence, causing a Glu-to-Lys amino acid change. Results of ISH showed punctuate signals in the nuclei of tumor cells., Conclusions: We suspect an association between HPV 16 infection and the development of this malignant occurrence., (© 2012 The International Society of Dermatology.)

Background: Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation., Objectives: To elucidate the immune evasion mechanisms of HPV, we have examined the density, dynamics, and subsets of dendritic cell (DC) types in non-inflammatory or inflammatory HPV-related skin lesions such as warts and Bowen's disease (HPV-Bowen), and compared the epidermal expression levels of macrophage inflammatory protein (MIP)-3α and E-cadherin., Methods: The expression of various DC markers, MIP-3α, and E-cadherin in the tissue samples obtained from patients with warts, HPV-Bowen and HPV-unrelated skin diseases was evaluated by immunohistochemistry. MIP-3α gene expression levels were examined in warts and HPV-Bowen by in situ hybridization (ISH) and real-time quantitative polymerase chain reaction (RT-qPCR)., Results: The numbers of Langerhans cells (LCs) and the expression levels of MIP-3α and E-cadherin were decreased in non-inflammatory warts and HPV-Bowen, as compared with normal skin. Both epidermal LCs and MIP-3α expression reappeared in inflammatory warts, associated with dermal infiltrates composed of many cytotoxic T cells and various subsets of DCs, while cellular infiltrates in HPV-Bowen contained many B cells and plasma cells with sparse infiltration of DCs. The upregulation of MIP-3α gene expression was confirmed in the inflammatory warts and HPV-Bowen by ISH and RT-qPCR., Conclusions: The depletion of LCs in the non-inflammatory warts and HPV-Bowen is associated with a down-regulation of expression levels of MIP-3α and E-cadherin in the lesional keratinocytes. MIP-3α expression is upregulated in lesional keratinocytes of inflammatory warts, with the subsequent recruitment of various DC subsets and cytotoxic T cells, whereas plasma cell-rich infiltration was induced in HPV-Bowen., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Human papillomaviruses (HPVs) have been detected in lesions of Bowen's disease (BD) and Bowen's carcinoma (BC); the invasive tumor retains the cytological characteristics of BD. Previous reports suggest that nestin-expressing hair follicle stem cells are undifferentiated and pluripotent, and nestin expression in some tumors indicates poor differentiation and high grade of malignancy. We identified HPV-DNA in BD (n=25) and BC (n=23) by in situ hybridization (ISH) analysis with INFORM(®) HPV III (Ventana Medical Systems. AZ, USA) and determined nestin expression by indirect immunohistochemical staining with anti-nestin polyclonal antibody (IBL, Gunma, Japan). We detected HPV-DNA in 68% of BD and in 87% of BC. In BD, 13 cases demonstrated the punctuate pattern, and four showed nestin expression. In BC, 19 cases showed the punctuate pattern and 16 showed nestin expression. HPV-DNA integrates into the host genome, and this is observed as the punctuate pattern on ISH. The nestin expression was statistically high in group of BC than BD (P<0.01). These results therefore suggest that HPV-DNA integrated in the genome of tumor cells of these diseases and contributed to malignant alteration. From the standpoint of tumorigenesis, BC might represent one type of poorly differentiated, high-grade squamous cell carcinoma.

Background: Human papillomavirus (HPV)-associated squamous cell carcinoma (SCC) and SCC in situ are often reported in the genital region. The association of HPV with SCC in the ungual and periungual skin is less well recognized, and verrucous lesions may undergo years of therapeutic attempts without a diagnostic biopsy., Objectives: To review the epidemiology, associations, and role of HPV in digital SCC and SCC in situ., Methods: The English-language literature reporting HPV-associated SCC and SCC in situ of the digits was reviewed., Results: HPV-associated SCC and SCC in situ were almost equally represented. The patients' ages ranged from 22 to 89 years, with men affected twice as often as women. HPV16 was the most common subtype. The tumors presented as persistent verrucae, present for an average of 5.3 years. Immune suppression was documented in only 6.8% of patients. Approximately 6% of cases required digital amputation., Limitations: Most of the information was obtained from case reports, some of which had limited data regarding the exact location of the tumor and the diagnostic and treatment course. HPV subtyping is not commonly performed in these tumors, which limited the number of reports that could be evaluated., Conclusions: The majority of digital HPV-associated SCCs or SCCs in situ involves the nailbed region. The clinical appearance is most commonly that of a periungual verruca. Tumors have a higher rate of recurrence after excision than SCC in other sites. Periungual and subungual warts caused by high-risk HPV subtypes pose a risk for malignant transformation in both immunocompetent and immunocompromised hosts., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)