Benign Human Papillomavirus Infection in Renal Transplant Recipients

Warts and cutaneous squamous cell carcinomas are common complications of immunosuppression. We studied a total of 189 renal transplant recipients clinically for such lesions. The incidence of warts increased steadily after transplant, such that of patients transplanted for more than 5 years, 92% were found to have warts and 65% had more than five warts each. DNA extracted from scrapings of their warts showed they carried the same human papillomavirus types as the general population, and not the unique set found on patients with epidermodysplasia verruciformis (who share with transplant recipients an increased incidence of warts and squamous cell carcinomas).     

TP53 polymorphism of exon 4 at codon 72 in cutaneous squamous cell carcinoma and benign epithelial lesions of renal transplant recipients and immunocompetent individuals: lack of correlation with human papillomavirus status

A common polymorphism at codon 72 of exon 4 encoding either arginine or proline has been shown to confer a susceptibility to the development of skin tumor in renal transplant recipients. Moreover, this polymorphism may affect proteolytic degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and represent a risk factor for human-papillomavirus-induced carcinogenesis. In this study, we analyzed the human papillomavirus presence and the TP53 allele distribution in cutaneous squamous cell carcinoma of renal transplant recipients and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant recipients with no history of skin cancer, 51 squamous cell carcinomas from immunocompetent patients, and 29 blood samples from immunocompetent individuals without skin cancer were investigated. Human papillomavirus DNA was detected using polymerase chain reaction performed with two pairs of primers (MY09-MY11 and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA was detected in 64% of squamous cell carcinoma and 79% of benign epithelial lesions from renal transplant recipients (NS) and only in 37% of squamous cell carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human papillomavirus types were predominant in squamous cell carcinoma from both renal transplant recipients and immunocompetent patients. Rate of arginine homozygosity in squamous cell carcinoma from renal transplant recipients was significantly higher (83%) than in immunocompetent patients with or without squamous cell carcinoma (60% and 59%, respectively). Our results suggest that TP53 arginine/arginine genotype could represent a potential risk factor for the development of squamous cell carcinoma in renal transplant recipients compared to immunocompetent patients. No association between TP53 arginine/arginine genotype and human papillomavirus status could be determined, however.     

Evaluation of human papillomavirus type 5 on frozen sections of multiple lesions from transplant recipients with in situ hybridization and non-isotopic probes.

Transplant recipients are at high risk to develop multiple cutaneous lesions after grafting. The frequency of the potentially oncogenic human papillomavirus (HPV) type 5 DNA was evaluated in cutaneous lesions taken from sun-exposed areas in transplant recipients (92 lesions and 5 samples from normal skin) and compared with a nontransplanted population (22 lesions and 7 samples from normal skin) using in situ hybridization and biotinylated probes to HPV types 1, 2, 5, 16 and 18. HPV type 5 DNA was identified in 8/92 cutaneous lesions of transplanted recipients: 3 warts, 1 case of seborrheic keratosis, 2 actinic keratoses and 2 keratoacanthomas. HPV type 5 DNA was not detected in 27 malignant tumors (8 basal cell carcinomas and 19 squamous cell carcinomas) from transplant recipients. HPV DNA type 5 was detected in only 1 case of squamous cell carcinoma from the general population. The presence of HPV DNA 5 was confirmed with Southern blotting in 2 out of 6 cases from transplant recipients. The reaction was negative with the squamous cell carcinoma from nontransplant recipients. These data indicate that the presence of HPV DNA type 5 is not very frequent; it can be detected with in situ hybridization and nonisotopic probe, which is easier to handle than Southern blot.     

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: a clinical and molecular biological study.

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis suffers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at greater than 35 years developing tumours about four times more rapidly than patients less than or equal to 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.     

Human papillomavirus infections in a group of renal transplant recipients

One hundred and twenty renal transplant recipients were investigated. Fifty-eight (48%) were found to have warts, 13 (11%) keratoses and six (5%) to have, or recently to have had cancers. The longer the time of immunosuppression, the greater the prevalence of warts; of those patients who had had their transplant for at least 5 years, 87% had warts. Those with a graft survival time of 10 years or more are at special risk of warts, keratoses and malignancy. Five (10%) of 50 women had genital warts, four of whom had internal lesions (vaginal, cervical or anal) and one developed a carcinoma of the vulva. These findings indicate the advisability of colposcopy for all female renal transplant recipients, a high risk group. Eighty-eight specimens from 42 patients were examined by DNA restriction enzyme analysis and cross hybridization for the presence and type of human papillomavirus (HPV). HPV DNA was detected in 66% of the warts examined, HPV2 and HPV4 occurring most often and HPV1 and HPV3 only infrequently. In sequential specimens from common hand warts of one individual, an HPV was found which could not be precisely identified but was related to HPV4. HPV16 was detected in a vaginal wart from one patient and an HPV6-related virus in a vulval wart of another. HPV DNA of an unknown type was demonstrated in one of 11 keratoses examined. With the probes used to examine the few samples of skin cancers available, HPV16 was found in a squamous cell carcinoma of the vulva, and faint bands from an unidentified type of HPV were detected in two squamous cell carcinomata from a patient's hand. One woman had plaque lesions morphologically and histologically resembling those found in epidermodysplasia verruciformis (EV). HPV5 was identified in these lesions. This is only the third reported case of HPV5, previously thought to be unique to EV, in a renal transplant recipient.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 clysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).     

Cutaneous squamoproliferative lesions in kidney transplant recipients: an investigation of specific Epstein-Barr virus expression

In a previous report we demonstrated Epstein-Barr virus expression in cutaneous squamous cell carcinomas from heart transplant recipients. In a comparative study, skin lesions from renal allograft recipients were investigated for the presence of Epstein-Barr virus. Thirty cutaneous squamoproliferative lesions from 10 kidney transplant recipients were examined for Epstein-Barr virus-specific gene expression. The techniques used for detection were polymerase chain reaction, in situ hybridization and immunohistochemistry. Epstein-Barr virus DNA was not detected by polymerase chain reaction in the neoplasias, and only single Epstein-Barr virus-positive carcinoma cells were shown by in situ hybridization in three cases of infiltrative squamous cell carcinomas. Immunohistochemistry for Epstein-Barr virus latent membrane protein 1 showed a negative result in all samples. These findings differ from our earlier investigations of cutaneous squamous cell carcinomas from heart transplant recipients where Epstein-Barr virus expressions were common. This may indicate that the part Epstein-Barr virus plays in the development of post-transplant, cutaneous squamoproliferative disorders is related to type of organ transplantation and/or grade of immunosuppression.     

Langerhans cells, inflammation markers and human papillomavirus infections in benign and malignant epithelial tumors from transplant recipients.

Organ transplant recipients frequently develop warts which progress toward premalignant or malignant lesions after a rather long grafting period. The local immune responses of such lesions (warts, condyloma acuminata, actinic keratoses, Bowen, basal and squamous cell carcinomas) was studied in 32 frozen skin specimens taken from 15 male transplant recipients and compared to similar lesions from the normal population. We studied the expression of T cell subsets, Langerhans cell phenotype, HLA class 1 (beta 2-microglobulin), HLA class 2 (DR antigen), and intercellular adhesion molecule 1 (ICAM 1). The presence of HPV infection was also considered, using in situ hybridization with biotinylated probes in order to examine the correlation with immunological markers. In the dermis, the lesions from grafted patients showed a moderate to intense inflammatory reaction of HLA-DR-positive cells. Most of these cells were CD4+ and CD8+ without any predominance of a single T cell subset. In the epidermis, most lesions were characterized by a reduced number of CD1-positive cells; this was concomitant with a decrease or a loss of beta 2-microglobulin expression by epithelial cells. HLA-DR antigen was not expressed by keratinocytes or tumoral cells in any specimen; ICAM 1 antigen was observed in a few cases. The expression of these markers was similarly modified with or without the presence of HPV DNA. Conversely, most lesions from non-immunocompromised patients, except warts, showed intense inflammatory reactions, with a predominance of CD4-positive cells and large foci of ICAM 1-positive cells. Expression of activation markers by keratinocytes occurred mainly in condylomas and squamous cell carcinomas. In the normal population, HPV infection was only detected in papilloma lesions. These data indicate, in lesions from grafted patients, a lack of effective immune response with partial inhibition of activation markers expressed by keratinocytes. It is conceivable that immunosuppressive treatment with solar exposure may also be responsible for the local immune deficiency and thus for the conversion of benign warts toward malignant lesions in grafted patients.     

Humane Papillomvirus-assoziierte Warzen bei organtransplantierten Patienten

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially indentifing patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.     

Use of topical immunomodulators in organ transplant recipients

Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular imiquimod, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of imiquimod in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of imiquimod and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical imiquimod in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions.     

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.     

Lifelong severe verrucosis associated with human papillomavirus type 2: report of a case with a 38-year follow-up

We describe a 67-year-old woman with disseminated warts which she had had for more than 38 years. The lesions consisted of common and plane warts, wart-like plaques and red-brownish macules similar to those in pityriasis versicolor. Furthermore, during follow-up, several solar keratoses, plaques of Bowen's disease and invasive squamous cell carcinomas were excised. The patient also had T-cell immunodeficiency of unknown aetiology. Histopathology demonstrated that all the warts showed the cytopathological features of common warts, but not those of the warts in epidermodysplasia verruciformis (EV). We investigated the presence of human papillomavirus (HPV) DNA in the warts by blot hybridization and molecular cloning and found that the lesions harboured HPV 2, but not EV–HPVs or other HPVs. In addition, the histopathological distribution of the viral DNA was confirmed in paraffin sections of warts from the patient at different ages by in situ hybridization. However, these investigations yielded negative results in specimens of Bowen's disease and invasive squamous cell carcinoma. These results demonstrated that the patient had been infected with HPV 2 from childhood, but the negative results for detection of DNA of HPV 2 in carcinomas from the patient do not support an oncogenic potential for HPV 2. In conclusion, HPV 2, an aetiological agent of common warts in the general population, may induce a lifelong severe verrucosis in some immunosuppressed patients.     

Warts and epidermoid carcinoma after renal transplantation

Kidney transplant recipients suffer in the long-term from several cutaneous disorders linked to the transplantation. We had the opportunity to observe several patients presenting with pre-epitheliomatous keratoses and cutaneous carcinomas associated with warts. We report herein on five cases that were subjected to a clinical, histological and virological study. Material and methods. Clinical and histological report. The patients were referred to use by the Kidney Transplantation Department of the Ed. Herriot Hospital (Lyon). They were examined clinically by one of us (S.E.). Virological studies. These were performed on warts, keratoses, keratoacanthomas and squamous cell carcinomas. Human papillomavirus (HPV) antigen was detected by indirect immunofluorescence using rabbit antibodies raised against group-specific HPV antigen; viral DNA was detected by in situ molecular hybridization using biotinylated probes of types 1a, 2a, 16, 18 in all cases and type 5 in 14 lesions under stringent conditions. DNA-DNA hybrids were revealed by an alkaline phosphatase enzymatic system. Results: (a) Clinical data are summarized in table I (see fig. 1-5). (b) Histological examination (fig. 6-9) showed either unequivocal squamous-cell carcinoma or keratoacanthoma . The overall architecture of the lesions was reminiscent of keratoacanthoma; however the lower limit was frequently not sharply demarcated; in that area, cells contained large basophilic nuclei exhibiting atypical features and numerous mitoses. The majority of lesions had an histological appearance reminiscent of warts (table III), with upper epidermal keratinocytes being vacuolized and containing basophilic (c) The results of virological studies (fig. 10-13) are summarized in table III. HPV group specific antigen was detected merely in 5 out of 33 lesions; in contrast, in situ molecular hybridization showed that 25 out of 33 lesions contained HPV DNA, with 14 of them containing the potentially oncogenic types 16 and 18. Only 2 lesions were positive with the prove HPV 5. Discussion. The overall incidence of cancers in Kidney transplant recipients (3 p. 100) is about 100 times higher than in control populations (17). Cutaneous carcinomas account for about 50 p. 100 of cancers. This incidence increases with time after transplantation and sun-exposure. The delay on onset of cutaneous malignancies is relatively long (4 to 7 years) (6,7) and becomes longer with a decreasing age of the patients at the time of transplantation, as can be noted in our cases. Apart from Blohme (1), most authors have reported a prevalence of squamous over basal-cell carcinoma. None of our patients presented basal-cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)     

Human papillomavirus infection in Netherton's syndrome

BACKGROUND: Netherton's syndrome (NS) is a hereditary disorder with dermatological signs (e.g. ichthyosis) and a complex immunological dysfunction. In immunodeficient individuals human papillomavirus (HPV) types are associated with carcinomas on non-mucosal sites. OBJECTIVES: To study the presence of HPV infection in different skin lesions of three male NS patients and to investigate a possible association between HPV and malignancies in NS. METHODS: Patient 1 had extraordinary widespread multiple skin carcinomas on sunlight-exposed areas, as well as common viral warts. Patient 2 showed disseminated viral plane warts that resolved spontaneously, and patient 3 was free of skin lesions suspicious for HPV infection; only pseudoepitheliomatous wart-like lesions as a symptom of ichthyosis were apparent. We performed nested polymerase chain reaction analysis of DNA from benign and malignant skin lesions and HPV-8 serology in these three patients. RESULTS: Antibodies to HPV-8 were not detectable in our patients; however, seven of 22 (31%) biopsies of the three NS patients were positive for HPV DNA. Epidermodysplasia verruciformis (EV) -associated HPV types and normal cutaneous types (HPV-2, HPV-28) were detected. Interestingly, only the patient with cutaneous carcinomas harboured, preferentially in malignant lesions, EV-HPV types (HPV-19, 23, 38 and HPV-RTRX9, closely related to EV-HPVs), whereas plane warts of patient 2 were positive for HPV-28. The pseudoepitheliomatous skin lesions were HPV-DNA negative in all investigated probes. CONCLUSIONS: These data in NS patients further confirm an association of EV-HPVs with non-melanoma skin cancer (NMSC) and suggest a possible carcinogenic role similar to that assumed for NMSC in transplant recipients. A complex immunological disorder facilitating EV-HPV infection, negative HPV serology and photochemotherapy may all have contributed to the unusual occurrence of multiple cancers in one of our NS patients.     

Merkel cell carcinoma in organ-transplant recipients: report of two cases with unusual histological features and literature review

BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ transplantation and are often associated with human papillomavirus (HPV). Merkel cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have been reported up till now, usually briefly, in organ transplant patients. METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of post graft, respectively. These were studied histologically and immunohistochemically, as well as virologically for the presence of HPV. A thorough literature review of all reported cases of Merkel cell carcinoma following solid organ transplantation was performed. RESULTS: Despite a typical immunophenotype, the tumors showed unusual histological features: both were epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma. Search for HPV by immunohistochemistry and PCR proved negative in both cases. CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is much rarer than other non melanoma skin cancers but may show unusual histologic features. HPV do not seem to be involved in its pathogenesis.     

Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases

OBJECTIVE: To assess the clinicopathologic features of basal cell carcinomas developing in organ transplant recipients. DESIGN: Case series. SETTING: University department of dermatology. PATIENTS: One hundred forty-six (7.2%) of 2029 transplant recipients followed up in our department who developed 176 histologically proven basal cell carcinomas. One hundred fifty-three random samples of basal cell carcinomas excised from nonimmunosuppressed patients served as controls. MAIN OUTCOME MEASURES: Clinical data were gathered from the medical records. Histologic slides were retrospectively reexamined. RESULTS: Basal cell carcinomas developed an average of 6.9 years after transplantation, sooner after heart than kidney transplantation, and showed a relative predilection for heart allograft recipients. The mean age of transplant recipients with basal cell carcinomas was significantly lower than that of controls (54.6 vs 69.8 years), especially for recipients of renal transplants, and a male preponderance was found (male-female ratio, 4.8:1 vs 1.3:1). In both groups, basal cell carcinomas were predominantly found on the head and neck, but extracephalic locations were significantly more frequent in transplant recipients (37.5%) than controls (24.5%). Histologically, superficial basal cell carcinomas were more frequent in transplant recipients than controls (33.6% vs 14.4%). The density of the peritumoral cell infiltrate was lower in tumors from transplant recipients compared with controls. The tumor thickness and the presence of epidermal ulceration did not differ significantly between the 2 groups. CONCLUSIONS: Basal cell carcinomas in transplant recipients show some clinicopathologic differences from their "ordinary" counterparts, namely, a younger age at development, male preponderance, more frequent distribution in extracephalic sites, and higher frequency of superficial subtypes.     

Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses.

Epidermodysplasia-verruciformis-associated human papillomavirus DNA has been demonstrated in squamous cell carcinomas and plucked hair from immunocompetent patients and renal transplant recipients. This study investigated the association between infection with epidermodysplasia-verruciformis-associated human papillomavirus, identified by the detection of viral DNA in plucked eyebrow hairs, and solar keratoses. These lesions are strongly predictive of squamous cell carcinoma. In a cross-sectional study 518 individuals were enrolled from a randomly selected sample of a subtropical Australian community. Epidermodysplasia-verruciformis-associated human papillomavirus DNA in eyebrow hair was detected using a nested polymerase chain reaction specific for epidermodysplasia-verruciformis-associated human papillomavirus types. Epidermo dysplasia-verruciformis-associated human papillomavirus DNA was present in 121 (49%) of 245 men and 116 (44%) of 262 women. There was a strongly significant increase in epidermodysplasia-verruciformis-associated human papillomavirus infection with age (p < 0.00001), with prevalences of 29% in the 25-39 y age group, 42% at 40-59 y and 65% in the 60-79 y age group. Among men there was a strong association between epidermodysplasia-verruciformis-associated human papillomavirus and solar keratoses with an odds ratio, adjusted for age, skin color, and occupational sun exposure, of 3.40 (95% confidence interval, 1.77-6.53). No such association was found among women [odds ratio 1.03 (95% confidence interval 0.59-1.77, after adjustment for the same factors)]. Differences in occupational sun exposure and smoking histories could not explain these apparently different associations between epidermodysplasia-verruciformis-associated human papillomavirus infection and solar keratoses in men and women. In conclusion, epidermodysplasia-verruciformis-associated human papillomavirus infection is associated with solar keratoses in men suggesting that epidermodysplasia-verruciformis-associated human papillomavirus infection, in conjunction with sex specific factors (like androgens), may be involved in neoplastic changes of keratinocytes.     

Seborrheic Keratosis-like lesions in patients with epidermodysplasia verruciformis

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by disseminated infection by human papillomavirus (HPV) and malignant transformation of the lesions in about half of the patients. Two phenotypes of EV have been described according to their propensity to develop malignant tumors. The benign form of EV presents a singular type of lesions comprised of flat warts widely disseminated. The malignant form of EV is highly polymorphic and presents as malignant skin tumors, predominantly basal and squamous cell carcinomas, on sun-exposed sites. The seborrheic keratosis-like (SK) lesions in patients of EV have been reported to be associated with the malignant phenotype. In this work, we documented the behavior of SK-like lesions in nine patients with EV, through clinical observations as well as histological and immunohistochemical findings. We suggest that the HPV infection may promote the occurrence of SK-like lesions in EV patients. Despite the fact that we did not observe any malignant transformation of these lesions in our series of patients, this possibility was not completely excluded.