High viral load of human wart-associated papillomaviruses (PV) but not β-PV in cutaneous warts independent of immunosuppression

Background  A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR).
Objectives  To determine the HPV types in warts from OTR, we assessed present infections of mucosal (α-PV), wart-associated (α-, μ- and ν-PV) and cutaneous HPV types (β-/γ-PV) in immunocompetent patients and OTR.
Patients/methods  Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human α-, β-, γ-, μ- and ν-PV. For frequent types viral load was determined by quantitative real-time PCR.
Results  Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P  <   0·01) and the number of multiple infections (62% vs. 17%, P  <   0·0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10⁵-fold higher compared with human β-PV in both cohorts.
Conclusions  The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.     

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.     

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.     

High prevalence of epidermodysplasia verruciformis-associated human papillomavirus DNA in actinic keratoses of the immunocompetent population

Skin cancers in both immunosuppressed and immunocompetent populations are associated with epidermodysplasia verruciformis human papillomavirus (EV-HPV) DNA. However, little is known about the prevalence of EV-HPVs in actinic keratoses in immunocompetent individuals. Actinic keratoses from 114 patients were classified as low-grade (n=76) or high-grade (n=38) according to the extent of histological atypia. HPV DNA was amplified from 54 frozen and 60 paraffin-embedded biopsy specimens by nested polymerase chain reaction (PCR) with several consensus and type-specific primers. PCR products were sequenced for typing. These results were compared with HPV detection in skin cancers (n=20) and Bowens disease (n=18). A broad spectrum of EV-HPV types including oncogenic HPV5 and HPV8 and partially characterized sequences were detected in actinic keratoses and cutaneous cancers. In actinic keratoses a higher prevalence of EV-HPV DNA was found in frozen tissues than in formalin-fixed tissues (85% vs 67%). There was no difference between the low- and high-grade actinic keratoses either in terms of EV-HPV DNA prevalence or the results of serological study using HPV8 virus-like particles. The detection rate of EV-HPVs was lower in skin cancers and Bowens disease. This would suggest involvement of EV-HPVs in the early stages of cutaneous oncogenesis.Dr. Fuchs has died since this article was completed.     

Viral DNA detection and RAS mutations in actinic keratosis and nonmelanoma skin cancers

Background Actinic keratosis (AK) is a well‐established precancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes. A number of viruses have been proposed to play a role in the development of nonmelanoma skin cancers (NMSC), but the most plausible evidence to date suggests that cutaneous human papillomavirus (HPV) is the key instigating factor. Objectives To evaluate the prevalence of HPV, cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein–Barr virus (EBV) and investigate their relationship with the presence of RAS gene mutations in cutaneous lesions obtained from nonimmunosuppressed patients. Methods HPV, CMV, HSV and EBV detection was performed using polymerase chain reaction (PCR) in skin biopsies (26 AK, 12 SCC and 15 BCC samples) that were collected from immunocompetent patients. The RAS mutation incidence was also investigated in all cutaneous lesions by use of PCR/restriction fragment length polymorphism and direct DNA sequencing. Results Seventeen out of 53 (32%) skin lesions were found to be positive for HPV DNA. The highest incidences of HPV infection were five of 15 (33%) in BCC and four of 12 (33%) in SCC specimens. The HPV incidence was eight of 26 (31%) in AK and eight of 53 (15%) in normal skin tissue. Twelve out of 53 (23%) skin lesions were CMV‐positive. The highest incidence of CMV infection was six of 15 (40%), observed in BCC specimens. The CMV incidence was two of 26 (8%) in AK and four of 12 (33%) in SCC. No normal skin biopsy was found to be positive for CMV. All cutaneous samples were negative for HSV and EBV DNA, as assessed by our PCR‐based assays. Only three samples, one AK (4%), one BCC (6%) and one SCC (8%), were found to carry a G>T transversion at the second position of HRAS codon 12. Both HRAS mutant SCC and BCC biopsies were HPV‐ and CMV‐positive, as well. Conclusions HPV DNA is detected in NMSC, AK and normal skin biopsies. Our results also indicate that CMV is involved in NMSC at higher levels than in premalignant lesions, whereas the virus was not detected in normal skin biopsies. HSV and EBV do not appear to be involved in the pathogenesis of cutaneous lesions. Moreover, we suggest that the HRAS codon 12 mutation is not a very common event in AK or NMSC. Finally, both viral infection and HRAS activation appear to represent independent factors in the aetiology of NMSC, samples of which were obtained from immunocompetent patients.     

Detection and typing of human papillomavirus in cutaneous warts of patients infected with human immunodeficiency virus type 1

BACKGROUND: Cutaneous warts are caused by human papillomavirus (HPV). To date, more than 120 different types of HPV are known, of which 80 have been completely characterized. Prevalence studies on types of HPV present in cutaneous warts have been carried out in immunocompetent individuals and immunosuppressed organ allograft recipients, but not in human immunodeficiency virus (HIV)-positive patients. OBJECTIVES: To determine the HPV types present in cutaneous warts of HIV-infected patients. METHODS: Twenty-five biopsies of cutaneous warts from HIV-infected patients and 14 samples from control non-HIV-infected patients were studied. HPV detection was performed by polymerase chain reaction using two sets of primers: MY09/MY11 and RK91. The type of HPV was determined by restriction fragment length polymorphism analysis and direct sequencing of the amplified products. RESULTS: HPV DNA was detected in 64% of cutaneous warts from HIV-infected patients and in 79% of samples from the control group. The HPV types identified in HIV-infected patients were: HPV 2 (38%), 57 (31%), 27 (12%), 6 (12%) and 7 (6%). HPV 2/27/57 predominated in both groups, being present in 81% of lesions from HIV-infected patients and 82% of samples from non-HIV-infected patients. HPV 6, a genital HPV type rarely found in cutaneous lesions, was detected in two warts from HIV-infected patients and in one lesion of the immunocompetent group. HPV 7, characteristically associated with butcher's warts, and recently detected in oral and perioral lesions of HIV-infected patients, was found for the first time in a non-facial lesion of an HIV-infected patient. CONCLUSIONS: This is the first study evaluating the prevalence of HPV types in cutaneous warts of HIV-infected patients and immunocompetent individuals in Brazil.     

Frequency and spectrum of HPV types detected in cutaneous squamous-cell carcinomas depend on the HPV detection system: a comparison of four PCR assays

BACKGROUND: The association of human papillomavirus (HPV) with cutaneous squamous-cell carcinomas (SCCs) has been described recently, but the frequency and spectrum of HPV types identified differed substantially in distinct studies. OBJECTIVE: Comparison of different PCR assays with respect to sensitivity and range of HPV types detected. METHOD: Cutaneous SCC were analyzed for HPV DNA using both consensus PCR assays with degenerate primers and PCR assays with nondegenerate primers derived from HPV types 5 and 8. RESULTS: HPV DNA was found in 50% of SCC specimens using degenerate primers. The rate of HPV-DNA-positive specimens increased to 69% when PCR assays with nondegenerate primers were applied in addition. The spectrum of HPV types detected with each of the PCR assays differed considerably. CONCLUSIONS: The frequency and spectrum of HPV types detected in cutaneous SCC strongly depends on the HPV detection system used and urges the need for standardization of HPV detection and typing in skin lesions in order to characterize HPV types predominating in distinct tumors.     

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.     

Mucosal human papillomavirus types in squamous cell carcinomas of the uterine cervix and subsequently on fingers

Human papillomavirus (HPV), especially type 16, is causally involved in the pathogenesis of anogenital cancer. There is an increasing number of reports of HPV infections in squamous cell carcinoma (SCC) of the fingers. A search of the Swedish cancer register covering the period 1958-94 inclusive for women with a history of genital and upper extremity SCC revealed 63 cases. Archival material from both cervical and cutaneous lesions was traced and analysed for the presence of HPV DNA in 32 of these patients. A newly developed 'neighbour primer' polymerase chain reaction (PCR) for HPV 16 DNA, aimed at overcoming the obstacle of cross-linked target DNA, was shown to be superior to conventional general and type-specific HPV PCR tests. HPV DNA was significantly more frequently found in digital tumours than in tumours at other cutaneous sites of the upper extremities [67% (10 of 15) vs. 7% (three of 43); P < 0.001]. Among 13 patients with a history of both cervical and finger SCC, HPV 16 was found in cervical samples from seven patients. From five of these seven patients, HPV 16 was also present in the corresponding finger lesions. The results support the hypothesis of a possible transmission of patients' genital HPV infections to fingers.     

Sunlight exposure and (sero)prevalence of epidermodysplasia verruciformis-associated human papillomavirus

Ultraviolet radiation (UVR) is associated with an increased risk of squamous cell carcinoma (SCC), which is in part due to immunomodulation. In addition, human papilloma virus (HPV), especially the epidermodysplasia verruciformis (EV)-associated types, may be involved. In view of the capacity of UVR to impair host resistance to infections, we investigated the relationship between solar exposure and the prevalence of cutaneous HPV. In a case-control study on skin cancer (320 controls and 156 patients) a lifetime-retrospective questionnaire on sun exposure was administered. The presence of DNA of HPV types 5, 8, 15, 20, 24, and 38 in plucked eyebrow hair and type-specific seroreactivity were assessed and analyzed in relation to estimated exposure. Sunburn episodes in the past, especially at age 13-20 y, appeared to be associated with an enhanced risk of EV-HPV DNA positivity. In contrast, a higher lifetime sun exposure was associated with a lower risk of HPV infection. These results indicate that UVR at erythematogenic doses increases the risk of EV-HPV infection, possibly due to impaired host resistance to HPV and/or a direct effect of UVR on viral replication. The favorable association between lifetime sun exposure and HPV prevalence, however, underscores the enigmatic role of HPV in skin carcinogenesis.     

Detection of high-risk human papillomavirus type 16/18 in cutaneous warts in immunocompetent patients, using polymerase chain reaction

Cutaneous warts are caused by human papillomavirus (HPV). Prevalence studies of the types of HPV present in cutaneous warts have been carried out more frequently in immunosuppressed patients. The present study was designed to study the association of high-risk HPV in cutaneous warts of immunocompetent patients. A total of 45 cases of cutaneous warts from various sites in immunocompetent subjects were analyzed for HPV. Samples included both archival material i.e., paraffin embedded and fresh tissue. Highly sensitive and comprehensive polymerase chain reaction (PCR) methodology for detection of HPV of high oncogenic potential, HPV 16/18, was employed. Human papillomavirus 16 was detected in 3 (6.6%) patients. None of the lesions demonstrated HPV 18. None of the cutaneous warts demonstrated histopathological features associated with dysplasia or neoplasia. The identification of HPV 16 in cutaneous warts, which are benign proliferations of the skin, further expands the spectrum of HPV-linked lesions. It remains of critical interest to determine whether these types are specifically associated with the development of malignant lesions analogous to those seen in anogenital cancer.     

Association of human papillomavirus 7 with warts in toe webs

Background There have been no studies on the prevalence of types of human papillomavirus (HPV) in cutaneous warts that focus on warts in toe webs (WTW). There is no documented association between HPV 7 and WTW. Objectives To explore the clinical and histopathological features of WTW, and the distribution of HPV genotypes in patients with WTW. Methods The study group consisted of 20 patients with WTW; 31 patients with typical verruca vulgaris (VV) were enrolled as the disease control group, and 53 patients with tinea pedis and 48 healthy volunteers were enrolled as the disease‐negative control group. Tissue specimens were analysed for clinical and histological features and distribution of HPV genotypes. Polymerase chain reaction (PCR)‐based direct sequencing, TA cloning and type‐specific PCR (TS‐PCR) were performed in the WTW and VV groups. Interdigital scale specimens from patients with tinea pedis and from healthy volunteers were analysed for HPV DNA by nested PCR and TS‐PCR (HPV 7). Results All the patients with WTW were male and nearly all were immunocompetent; their mean age was 41 ± 10 years. The lesions presented mainly as soft, friable and vegetating clusters. HPV 7 was the predominant genotype in WTW with a frequency of 80% (16/20). Fourteen specimens were taken for histopathological examination. The most frequent histological results (seven out of 14) revealed characteristics of HPV 7 infections such as heavily stained cells containing medium‐sized keratohyaline granules and a pronounced hyperkeratosis with parakeratosis. TA cloning showed that the sequence shared 90% or more homology with the HPV genotype in direct sequencing. No HPV 7 DNA was found in the scales taken from toe webs without warts. Conclusions This is the first study evaluating the prevalence of HPV types in WTW and the first report of the association between HPV 7 and specific subgroups of patients with warts.     

Detection of human papillomavirus DNA by PCR in semen from patients with and without penile warts.

OBJECTIVES--To determine the prevalence of urethral HPV infection, as indicated by the presence of HPV DNA in semen, in males with and without penile warts. DESIGN--Prevalence study of HPV types 6/11 and 16 DNA using PCR and Southern blot hybridisation analysis of semen. SETTING--Department of Genitourinary Medicine, Blundell Street Clinic, Leeds General Infirmary and the Assisted Conception Unit (ACU) Kings' College, London. SUBJECTS--Patients attending the Genitourinary Clinic for treatment of sexually transmitted diseases including penile warts and males attending Kings' ACU for investigations of infertility. MAIN OUTCOME MEASURES--HPV DNA detected by polymerase chain reaction (PCR) and/or Southern blot hybridisation in semen. RESULTS--HPV DNA was detected by PCR in 23 of 27 (85%) specimens from patients attending the GUM clinic for treatment of genital warts and in one of two specimens from patients attending the clinic for other conditions. By Southern blot, nine (33%) of the 29 specimens from GUM clinic patients were HPV DNA-positive. HPV DNA was detected by PCR in 43 of 104 (41%) of specimens from males attending the ACU, whilst 70 of these tested by Southern blot hybridisation were all negative for HPV DNA. CONCLUSIONS--The data suggest that urethral HPV infections, as indicated by the presence of HPV DNA in semen, are prevalent in males with and without genital warts.     

Changes in HPV infection in patients with anogenital warts and their partners.

OBJECTIVES--To investigate the relationship between clinical findings and the detection of human papillomavirus (HPV) DNA in a range of anatomical sites in patients with and without anogenital warts. SUBJECTS--Men and women with a clinical diagnosis of anogenital warts, or a current partner with anogenital warts. SETTING--A department of genitourinary medicine in central London. METHODS--The anogenital areas of the patients were thoroughly examined using a colposcope before and after application of acetic acid. Different types of specimens were taken from a variety of anatomical sites. Superficial skin sampling was performed by the application of slides covered with "Superglue" (SG) to clinically normal and abnormal areas of anogenital skin. The presence of human cells in the SG samples was confirmed by detection of the beta-globin gene using the polymerase chain reaction (PCR). HPV DNA was extracted from the specimens and amplified by using consensus primers with the PCR. HPV types 6, 11, 16, 18, 31 and 33 were identified by Southern blotting followed by hybridisation. RESULTS--In women, HPV DNA was detected in 83% of wart biopsies, 29% of cervical biopsies, 36% of cervical scrapes, 25% of urethral loop specimens, 37% of vaginal washes and 33% of rectal swab specimens. In men, HPV DNA was detected in 67% of wart biopsies, 37% of urethral loop specimens and 12% of rectal swab specimens. Of the SG samples containing the beta-globin gene, 49% from women and 50% from men contained HPV DNA. HPV DNA was not detected in buccal scrapes and serum samples from women or men. Of all specimens with detectable HPV DNA, there was evidence of a single HPV type in 41%, multiple types in 48% and undetermined types in 11%. Samples taken from different sites of a patient tended to have HPV types in common. Sexual partners, however, did not consistently have HPV types in common. CONCLUSIONS--HPV DNA was distributed widely in the anogenital area, in warts, acetowhite areas and clinically normal skin. The SG technique was well tolerated by patients and produced results consistent with other findings. Sampling from a single site of the genitalia on one occasion may significantly underestimate the infection rate with HPV. Multifocal infection of the anogenital area with HPV should be taken into consideration when interpreting epidemiological studies and management strategies.     

132例皮肤疣组织人乳头瘤病毒分型检测

目的 探讨皮肤疣组织中人乳头瘤病毒（HPV）的感染率和病毒型别。方法 门诊皮肤疣患者132例中寻常疣46例,跖疣38例,扁平疣48例。以特异性DNA序列为模板设计引物,进行PCR扩增,电泳,对结果进行分析。 结果 132例皮肤疣中,HPV阳性128例,感染率为97.0%,其中HPV2型阳性111例,感染率为84.1%。寻常疣、跖疣感染主要为HPV2、HPV1型,扁平疣感染主要为HPV2、HPV10、HPV3、HPV1型。89例为多重感染,感染率为67.4%,其中二重感染率为41.7%（55例）,三重感染率为21.2%（28例）,四重感染率为4.6%（6例）;寻常疣多重感染率为50.0%（23/46）,跖疣为76.3%（29/38）,扁平疣77.1%（37/48）。多重感染中,以HPV1 + 2型最多,有35例（39.3%）,其次为HPV1 + 2 + 10型,有12例（13.5%）。 结论 遵义皮肤疣感染以HPV2型为主,其次为1型;2型与多种皮肤疣感染有关;皮肤疣中多重感染率较高,其中扁平疣多重感染率最高;新发现HPV3、10型感染寻常疣,HPV10型感染跖疣,HPV1、7型感染扁平疣。     

SOUTHERN BLOT ANALYSIS OF SKIN BIOPSIES FOR HUMAN PAPILLOMAVIRUS DNA: RENAL ALLOGRAFT RECIPIENTS IN SOUTH-EASTERN QUEENSLAND

The 104 skin biopsies from 34 patients who attended a Renal Transplant Unit in Brisbane over 12 months included 40 squamous cell carcinoma (SCC), 22 solar keratoses, 4 hyperkeratoses, 18 warts and 11 basal cell carcinoma (BCC). Human papillomavirus (HPV) DNA was identified by Southern blot hybridisation using, as individual probes, purified insert DNA from recombinant HPV 1, 2, 3 or 3/10, 4, 5 or 5/8, 7, 11, 16, 18 and 41 under relaxed conditions and characterised by restriction enzyme analysis and Southern blot hybridisation under more stringent conditions. Genomic HPV DNA was characterised in 7 skin biopsies from 4 renal allograft recipients (RARs): HPV 1A in a SCC (20 copies/cell) and a BCC (10 copies/cell) from the one patient, HPV 36 (20 copies/cell) in a SCC, HPV 1A (1000 copies/cell) in a wart and HPV 2B (200-800 copies/cell) in 3 warts from the one patient. Only HPV 1A in the SCC exhibited a significant degree of subtype variation. HPV DNA was identified in another 5 skin biopsies from another 4 RARs: HPV 3A in a wart and a hyperkeratosis, HPV3/10-related DNA in 2 solar keratoses and HPV5/8-related DNA in another (20-50 copies/cell). The incidence of HPV 5 (or 5-related HPVs) in RAR SCC was very low and that of HPV DNA in RAR warts was lower than that recorded elsewhere but this was not due to insensitivity of the assays. There was no evidence for a role for HPV in the aetiology of skin cancer in RARs in south-eastern Queensland but the possibility remains that as yet unidentified HPV types are involved.     

Human beta papillomavirus DNA study in primary cutaneous squamous cell carcinomas and their corresponding metastases

The association between beta human papillomavirus (HPV) types and cutaneous squamous cell carcinomas (cSCCs) is controversial. Several studies have found such an association, especially at early stages of carcinogenesis, but the presence of beta HPV types in aggressive cSCCs has only been reported in three patients previously. We aimed to search for beta HPV DNA in primary cSCCs and their corresponding lymph node metastases in a series of patients. The presence of DNA from 25 beta HPV types was determined using a multiplex PCR protocol in 35 primary cSCCs from 35 patients and their corresponding lymph node metastases. DNA from beta HPV types was detected in 9 % of primary cSCCs and in 13 % of metastases. No primary cutaneous SCC or lymphatic metastases were found to share the same HPV DNA. These data suggest that beta HPV types do not play an etiopathogenic role in advanced stages of squamous cell carcinogenesis.     

Human papillomavirus typing of warts and response to cryotherapy

Background Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). Objective The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. Methods Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. Results An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. Conclusion This study demonstrates that HPV type can be determined from wart parings. HPV‐2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population.     

Preliminary study of analyzing mucosal human papillomaviruses in cutaneous warts by restriction fragment mass polymorphism

Cutaneous human papillomavirus (HPV) types 1, 2, 4, 7 and 57 are reportedly found in cutaneous warts. However, there are few reports that have investigated the prevalence of mucosal HPV types in cutaneous warts. The aim of this study is to investigate the prevalence of mucosal HPV types in patients with cutaneous warts and to determine any association between HPV types and patient characteristics. We analyzed 62 wart samples that were taken from patients who were diagnosed with cutaneous warts, and 30 normal skin samples were used as negative control. We recorded the following characteristics: sex, age, type of warts, duration of warts, number of warts and patient's immune status. A matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry (MS)‐based restriction fragment mass polymorphism (RFMP) assay was used for HPV genotyping. Of the total 62 wart samples, 50 samples (81.6%) were positive for HPV genotypes. All of the negative controls (30 samples) using normal skin showed negative reaction. Mucosal HPV types (49 samples, 84.4%) were highly detected, and high‐ or probable high‐risk HPV types (39 samples, 67.2%) were more common than lower risk HPV types (10 samples, 17.2%). A statistically significant association was observed between sex, age, duration of warts and the risk of HPV types. To the best of our knowledge, this is the first study to use the RFMP assay to analyze cutaneous wart‐associated mucosal HPV types. The high prevalence of high‐risk and probable high‐risk HPV in this study is of great significance.