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Photodynamic therapy with topical delta-aminolaevulinic acid for the treatment of plantar warts.

Treatments currently employed for plantar warts are often painful (electrosurgery, cryotherapy) and not always effective (keratolytic agents). In this paper we investigate the effect of photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) on plantar warts. In order to remove the superficial hyperkeratotic layer of the warts an ointment containing 10% urea and 10% salicylic acid was applied for 7 days. After gentle curettage, a cream containing 20% ALA was applied under an occlusive dressing for 5 h on 64 warts, while 57 warts (controls) received only the vehicle. Both the ALA-treated warts and the controls were irradiated using a visible light lamp (with a range of 400-700 nm, peaking at 630 nm). The light dose was 50 J/cm(2). Patients were followed-up for 22 months. Two months after the last irradiation session 48 (75.0%) out of 64 ALA-PDT treated warts had resolved. By contrast only 13 (22.8%) of the 57 control warts had done so. During the treatment a few patients complained of a mild burning sensation. The absorption of ALA by the verrucous tissue was demonstrated by in vivo fluorescence spectroscopy. This study shows that topical ALA-PDT can be an alternative treatment for plantar warts. Further studies will be necessary in order to optimize the concentration of ALA and duration of treatment.

Administration, Topical↗

Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study.

The purpose of this pilot study was to determine if photodynamic therapy with topical application of 5-aminolaevulinic acid followed by irradiation with incoherent filtered and unfiltered light (ALA-PDT) is an effective therapy for recalcitrant hand and foot warts. In 30 patients with recalcitrant warts, 49 regions with a total of 250 warts were randomized to one of the following five treatments: (i) ALA-PDT with white light applied three times within 10 days (W3); (ii) ALA-PDT with white light applied once (W1); (iii) ALA-PDT with red light applied three times within 10 days (R3); (iv) ALA-PDT with blue light applied three times within 10 days (B3), and (v) cryotherapy applied up to four times within 2 months (CRYO). The ALA-PDT treatment modality was repeated in case of partially responding warts. Significantly more warts were completely healed after W3 and W1 than after R3, B3 and CRYO (P < 0.01): 73% of the warts treated with W3 were completely healed, 71% after W1, 42% after R3, 23% after B3 and 20% after CRYO. No scars were observed in the ALA-PDT treated areas and patients treated for foot warts were all able to walk after the treatment. No recurrences in completely responding ALA-PDT treated warts were observed after 12 months of follow-up. In conclusion, photodynamic therapy with topical 5-aminolaevulinic acid followed by irradiation with white light is a promising treatment for recalcitrant hand and foot warts.

Administration, Topical↗

[Efficacy and benefit of a 5-FU/salicylic acid preparation in the therapy of common and plantar warts--systematic literature review and meta-analysis].

BACKGROUND: (1) Salicylic acid (SA) and 5-Fluorouracil (5-FU) are effective drugs in wart therapy. (2) In Germany, increasing data on the benefit and the economic efficiency of drugs at Level I of evidence-based medicine are needed. METHODS: Evaluation of the effectiveness and benefits of a drug combination containing 0.5 % 5-FU and 10% SA in the therapy of (a) common and (b) plantar warts in form of a two-step procedure--(1) Systematic literature analysis, (2) Meta-analysis of the randomised-controlled studies (RCTs). RESULTS: (1) The efficacy of 5-FU/SA therapy was tested in a total of 625 patients (n=8 RCTs) with common warts and 101 patients (n=4 RCTs) with plantar warts. The therapeutic effect across all studies in common warts was 63.4% response (complete healing) for 5-FU/SA vs. 23.1% for the 5-FU-free controls, respectively. In plantar warts, the response was 63.0% vs. 11.0%. (2) A meta-analysis of n=7 RCTs on common warts (n=325 patients) showed a mean risk difference of 0.42 (CI 0.34-0.50, p < 0.05), thus a significant superiority of 5-FU/SA over SA. A comparable result was also found for plantar warts. CONCLUSION: The combination of 5-FU and SA is an effective and beneficial therapy for common and plantar warts.

Aspirin↗

Dermojet delivery of bleomycin for the treatment of recalcitrant plantar warts.

BACKGROUND: Plantar warts may cause significant morbidity. Intralesional bleomycin is effective. When bleomycin is injected with a needle and syringe, it is difficult to prevent the bleomycin from infiltrating the dermis adjacent to the wart, producing unnecessary acute pain, persistent pain, and potential sloughing of normal adjacent skin. Efficacy of delivery by dermojet is not yet established. OBJECTIVES: To assess the response of recalcitrant plantar warts to bleomycin delivered by dermojet. METHODS: A total of 47 patients with 138 plantar warts present for more than 2 years and resistant to 10 cycles of cryosurgery, were recruited. Bleomycin (1 U/ml) was delivered intralesionally by dermojet at 5-week intervals for 25 weeks. RESULTS: Out of 138, 124 (89.9%) plantar warts showed complete or partial clearance after one to five sets of bleomycin injections. The recurrence rate was 6/138 (4.4%), and 8/138 (5.8%) warts failed to clear. The reduction in mean surface area of the plantar warts after each set of bleomycin injections compared to baseline surface area was statistically significant. Local side effects were similar to other methods of delivery. No systemic side effects were reported. CONCLUSIONS: This study assesses therapeutic efficacy of bleomycin delivered by dermojet in solely recalcitrant plantar warts. It provides preliminary evidence that this method of delivery may benefit a group of patients with particularly recalcitrant plantar warts and is safe and easy to use in routine dermatology practice.

Antimetabolites, Antineoplastic↗

The descriptive epidemiology of warts in British schoolchildren.

This study set out to determine the prevalence and predictors of warts in British schoolchildren by analysing medical examination data from a national birth cohort study of 9263 British children born 3-9 March 1958. The prevalence of visible warts, according to a medical officer, at the age of 11 was 3.9% (95% confidence intervals 3.5-4.3) and 4.9% (95% confidence intervals 4.5-5.4) at 16. Of the 364 children noted to have warts at the age of 11,337 (93%) no longer had warts at 16. Residence in the south of Britain, having a father with a non-manual occupation, being an only child, and belonging to an ethnic group other than white European were all associated with a decreased risk of visible warts. Region of residence was the strongest predictor of wart prevalence. There were no sex differences in wart prevalence. Warts represent a common source of morbidity in British schoolchildren. Future studies should take into account age, regional factors, social class, family size and ethnic group when comparing wart sufferers with other subjects.

Adolescent↗

Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals.

BACKGROUND: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established. OBJECTIVES: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals. METHODS: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks). RESULTS: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11-29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure. CONCLUSIONS: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.

Administration, Cutaneous↗

Human papillomaviruses in anogenital warts in children: typing by in situ hybridisation.

OBJECTIVE: To identify the types of human papillomaviruses found in anogenital warts in children and to relate these to clinical and social information. DESIGN: In situ hybridisation using biotin labelled DNA probes to 11 types of human papillomavirus was performed on biopsy specimens from 17 children with anogenital warts. SETTING: Nuffield department of pathology and the department of dermatology, Oxford. PATIENTS: Children in one group were referred by general practitioners or paediatricians to the dermatology department, where biopsies were performed. The other children were seen in four different hospitals, and biopsy specimens were submitted to the laboratory at the physician's or pathologist's request. RESULTS: Of the 17 biopsy specimens, 10 contained cells positive with a probe to a genital human papillomavirus type (types 6 or 11), while six were positive with a skin virus type (types 2 or 3). One was negative. The virus type present bore no relation to the site or appearance of the warts. The virus type did, however, appear to correlate with groups of children. Skin types were commoner in older children (over 4 years), in those with a relative who had skin warts, and in children with warts elsewhere; there was no relation with the child's sex and no suspicion of sexual abuse in these children. These circumstances suggested non-sexual transmission, such as autoinoculation. In contrast, genital types were commoner in girls, in children under 3 years, in children with relatives with genital warts, and in those with no warts elsewhere. Nevertheless, there was suspicion or evidence of sexual abuse in only half these children, suggesting that other routes of transmission--for example, perinatal--might have been implicated. CONCLUSION: Anogenital warts in children may contain either skin or genital wart virus type. Although the type of human papillomavirus present may give some indication of the likely mode of transmission, this can be interpreted only in conjunction with all available clinical and social information. The type of virus does not provide proof of the presence or absence of sexual transmission.

Anus Diseases↗

A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.

OBJECTIVE: To examine biopsy specimens of tissue immediately adjacent to anogenital (AG) warts which had been treated with either cryotherapy plus subcutaneous interferon (IFN) alpha 2a or cryotherapy alone, for histological features of (a) human papilloma virus (HPV) infection (b) localised cellular immune responses, to further characterise any cellular immune infiltrates with tissue immunocytochemistry, and to relate any histological, immunocytochemical findings to the treatment response of nearby AG warts. DESIGN: A randomised placebo controlled observer blind study. SETTING: Genitourinary Medicine clinic, Department of Immunopathology, Royal Victoria Hospital, Belfast, N. Ireland. SUBJECTS: Thirty patients with AG warts; 16 treated with IFN alpha 2a plus cryotherapy, and 14 treated with cryotherapy alone. OUTCOME MEASURES: (1) Light microscopic features associated with HPV infection and local cellular immune responses. (2) Indirect immunofluorescence detection of the following cell surface markers: HLA DR, alpha one antitrypsin, CD1, CD3, CD4, CD8, CD22. (3) Clinical response of AG warts to treatment. RESULTS: In pre-treatment biopsies only non specific indicators of HPV infection (acanthosis, 29/30 biopsies, and hyperkeratosis, 7/30 biopsies) were seen on light microscopy. Mononuclear cells were seen both throughout the upper dermis and centred around dermal blood vessels in 19/30 (63.3%) biopsies, and infiltrating into the epidermis in 12/30 (40%) biopsies. On indirect immunofluorescence CD3, CD8, CD4 antigen was detected on the surface of cells throughout the upper dermis in 24/29 (82.7%), 15/29 (51.7%), and 3/29 (10.3%), of biopsy specimens respectively. CD3 antigen, CD8 antigen and CD4 antigen was detected on the surface of cells infiltrating into the epidermis in 18/29 (62%), 7/29 (24.1%), and 6/29 (20.7%) of biopsy specimens respectively. CD1 antigen was seen on the surface of dendritic cells throughout the epidermis in all specimens; CD1 positive cells infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS: (1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts.

Adolescent↗

New patient-applied therapy for anogenital warts is rated favourably by patients.

Our objective was to determine patient attitudes to having genital warts, and their perceptions of their treatment with imiquimod and other therapies. As an adjunct to a clinical trial in which patients with external genital warts were treated with imiquimod 5% cream until their warts cleared or for up to 16 weeks, quantitative questionnaires consisting of multiple choice questions and 5-point rating scales were completed prior to, and at the end, of the study period. Pre-study and post-study questionnaires were completed by 902 and 629 patients, respectively. Patients expressed a definite concern about genital warts. The majority of patients (70%) had been previously treated for genital warts, and expressed dissatisfaction with their previous therapies. Of patients treated with imiquimod in this study, 82% reported that their warts decreased in size; this occurred within the first 4 weeks for 78% of patients. Sixty-one per cent of patients perceived that their warts completely cleared within the 16-week treatment period. Patients rated imiquimod 5% cream as better than other genital wart therapies in terms of overall satisfaction, time to clearance, convenience and lack of associated pain. In conclusion, patients rated imiquimod 5% cream as an effective treatment which clears warts in an acceptable length of time causing minimal pain and is convenient to use.

Administration, Topical↗

Condylomata acuminata (genital warts). An epidemiologic view.

The understanding of condylomata acuminata (genital warts) has been enhanced by the recent development of diagnostic methods. Forty-two types of human papillomavirus were identified up to 1985, and at least sixteen types were involved in genital warts. The incidence of genital warts is around 0.1% in the general population and more than 0.5% in young persons. The incidence is known to be increasing rapidly and exceeding the incidence of genital herpes. Females are more prone to be affected. The epidemiologic evidence supporting the relationship between genital warts and genital cancer is overwhelming. The evidence also speaks for a strong correlation between genital warts and verrucous carcinoma of the genitalia, bowenoid papulosis, and laryngeal papilloma. The person having genital warts may also have other cutaneous warts. This observation is compatible with the finding that types of human papillomavirus involved in other cutaneous warts were found in genital warts. In view of the never and easier ways of diagnosing nonconspicuous condyloma acuminatum and the potential for malignant transformation of condyloma acuminatum, it is strongly recommended that patients should be followed up periodically for early detection of neoplasia.

Age Factors↗

Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function.

Defects in chromosomes or mitotic spindles activate the spindle checkpoint, resulting in cell cycle arrest at prometaphase. The prolonged activation of spindle checkpoint generally leads to mitotic exit without segregation after a transient mitotic arrest and the consequent formation of tetraploid G(1) cells. These tetraploid cells are usually blocked to enter the subsequent S phase by the activation of p53/pRb pathway, which is referred to as the G(1) tetraploidy checkpoint. A human homologue of the Drosophila warts tumor suppressor, WARTS, is an evolutionarily conserved serine-threonine kinase and implicated in development of human tumors. We previously showed that WARTS plays a crucial role in controlling mitotic progression by forming a regulatory complex with zyxin, a regulator of actin filament assembly, on mitotic apparatus. However, when WARTS is activated during cell cycle and how the loss of WARTS function leads to tumorigenesis have not been elucidated. Here we show that WARTS is activated during mitosis in mammalian cells, and that overexpression of a kinase-inactive WARTS in Rat1 fibroblasts significantly induced mitotic delay. This delay resulted from prolonged activation of the spindle assembly checkpoint and was frequently followed by mitotic slippage and the development of tetraploidy. The resulting tetraploid cells then abrogated the G(1) tetraploidy checkpoint and entered S phase to achieve a DNA content of 8N. This impairment of G(1) tetraploidy checkpoint was caused as a consequence of failure to induce p53 expression by expressing a kinase-inactive WARTS. WARTS thus plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G(1) tetraploidy checkpoint.

Actins↗

Risk factors for genital and anal warts in a prospective cohort of HIV-negative homosexual men: the HIM study.

OBJECTIVE: The objective of this study was to determine the prevalence, incidence, and risk factors for genital and anal warts in HIV-negative homosexual men in Sydney. STUDY DESIGN: The authors conducted a prospective cohort study. Participants were asked whether they had had genital and anal warts at each interview. Details of lifetime sexual contacts and sexual behaviors in the last 6 months were collected. RESULTS: Among 1,427 men recruited, 8.9% and 19.6% reported a history of genital and anal warts at baseline, respectively. Incidence rates for genital and anal warts were 0.94 and 1.92 per 100 person-years, respectively. In multivariate analysis, both incident genital and anal warts were associated with younger age. In addition, incident genital warts was associated with insertive fingering (P trend = 0.018), whereas incident anal warts was associated with insertive fingering (P trend = 0.007) and insertive fisting (P trend = 0.039). CONCLUSIONS: Anal warts were twice as common as genital warts. Fingering and other manual sexual practices may be an important transmission route for both.

Adolescent↗

Common association of HPV 2 with anogenital warts in prepubertal children.

Anogenital (AG) warts in 31 prepubertal children were HPV typed by nonisotopic in situ hybridization (NISH) using digoxigenin-labeled probes for human papilloma virus (HPV) types 1-5, 6, 11, 16, 18, 31, and 33. Mode of transmission was determined from historical, clinical, and laboratory data independent of HPV typing. HPV 2 was detected most commonly (13/31 warts) followed by HPV 6 (7/31), HPV 11 (5/31), and HPV 16 (1/31). Although not reaching statistical significance, our results suggested that a mucosal HPV type (6, 11, 16) in a child's AG warts implied transmission from mucosal warts and conversely cutaneous HPV 2 transmission from warts at a cutaneous site. HPV typing provided no helpful information regarding actual mode of transmission of AG warts in these children. The high prevalence of HPV 2 in children's AG warts and the low prevalence of sexual abuse (2 of 31 children) found in this study suggest innocent auto- or heteroinoculation from cutaneous warts may be a common means by which children acquire AG warts.

Anus Diseases↗

Relationship of genital wart burden to therapeutic response to fluorouracil/epinephrine injectable gel.

The efficacy of a single cycle of a new therapy for genital warts, intradermal fluorouracil/epinephrine (5-FU/epi) injectable gel, has been evaluated in 2 large pivotal trials; the objective of this study was to evaluate a second cycle of treatment. Twenty-two patients with total wart areas of 5-447 mm2 were treated with up to 2 cycles of < or =6 treatments of 5-FU/epi gel. After the first cycle of treatments, patients with warts showing a partial response or no response or new warts were continued into a second cycle. Seventy-three per cent (16/22) of patients had complete responses. Patients with total wart areas < or = 100 mm2 tended to respond completely in the first cycle of treatment (average 4.7 treatments). Patients with numerous warts or large total wart areas (>100 mm2) required an average of 7.5 treatments to achieve a complete response. Thus, a second treatment cycle may be appropriate for difficult-to-treat patients with numerous warts or large total wart areas.

Body Surface Area↗

Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a single-blinded, randomized, and controlled trial.

BACKGROUND: Warts occur commonly in humans. Destructive modalities are generally the first physician-administered therapy. Other treatment options include immunotherapy. Intralesional immunotherapy using mumps, Candida, or Trichophyton skin test antigens has proved efficacy in the treatment of warts. OBJECTIVES: To determine rates of wart resolution in response to injection of antigen alone, antigen plus interferon alfa-2b, interferon alfa-2b alone, and normal saline; and to compare response according to viral type, major histocompatibility complex antigens, and peripheral blood mononuclear cell proliferation to autologous human papillomavirus antigen before and after injection. DESIGN: Randomized, single-blinded, placebo-controlled, clinical trial. SETTING: Medical school-based dermatology department. PATIENTS: Two hundred thirty-three patients clinically diagnosed as having 1 or more warts. Main Outcome Measure Clinical resolution of warts in response to intralesional immunotherapy. RESULTS: Responders were observed in all treatment arms, but were significantly more likely to have received antigen (P<.001). Resolution of distant untreated warts was observed, and was significantly more likely in subjects receiving antigen (P<.001). Interferon did not significantly enhance the response rate (P = .20) and did not differ from normal saline (P = .65). No viral type or major histocompatibility complex antigen correlated with response or lack of response (P>.99 and P = .86, respectively). A positive peripheral blood mononuclear cell proliferation assay result (2 times pretreatment levels) was significantly more likely among responders (P = .002). While there was no significant difference in response based on sex (P = .56), older subjects (>40 years) were less likely to respond (P = .01). CONCLUSIONS: Intralesional immunotherapy using injection of Candida, mumps, or Trichophyton skin test antigens is an effective treatment for warts, as indicated by significantly higher response rates and distant response rates in subjects receiving antigen. Viral type and major histocompatibility complex antigens did not seem to influence treatment response. Response is accompanied by proliferation of peripheral blood mononuclear cells to human papillomavirus antigens, suggesting that a human papillomavirus-directed cell-mediated immune response plays a role in wart resolution.

Adult↗

Pulsed dye laser treatment of warts.

OBJECTIVE: To determine the safety and efficacy of the flashlamp-pumped pulsed dye laser for the treatment of uncomplicated and recalcitrant warts. DESIGN: Observational study. PATIENTS: A total of 142 patients with 703 recalcitrant and 25 previously untreated warts consecutively referred to two tertiary care laser centers from July 1993 through January 1994. INTERVENTION: Photocoagulation with the flashlamp-pumped pulsed dye laser. MAIN OUTCOME MEASURES: Complete resolution of treated warts after a follow-up ranging from 3 to 9 months. RESULTS: The overall response rates were 99% for body, limb, and anogenital warts; 95% for hand warts; 84% for plantar warts; and 83% for periungual warts. Side effects were limited and infrequent. CONCLUSION: Pulsed dye laser therapy is a highly effective and safe method used to selectively destroy warts without damaging the surrounding skin.

Adolescent↗

Use of HPV 1 capsids produced by recombinant vaccinia viruses in an ELISA to detect serum antibodies in people with foot warts.

A sandwich ELISA was developed to detect HPV antibodies using HPV 1 capsids that were purified from recombinant vaccinia virus-infected cells and a monoclonal antibody to the HPV 1 L1 protein. Sera from 91 college-aged women who had been previously screened for HPV 1 antibodies by immune precipitation of capsid proteins were tested by ELISA. A cutoff point was established independently of other criteria based on the assumption that the ELISA values came from a mixture of two Normal distributions representing seropositive and seronegative individuals. It was found that the data fit this model best when the natural log of the ELISA (+0.5 to make all of the values positive) was used. Positive sera were shown to react with a conformational epitope(s) on the L1 protein. In the population reporting foot warts, 16 of 18 (89%) had ELISA values above the cutoff. This compared to 38 of 73 (53%) positives in the population reporting no history of foot warts. The odds ratio for the association of the ELISA reactivity with foot warts was 7.23 (95% CI 1.53, 69.4; P < 0.01). There was no significant association between the ELISA reactivity and wart infections reported at other sites. The average of the log ELISA values for individuals never reporting foot warts was -0.223 (SD 0.468), whereas the average value for individuals reporting foot warts within 10 years was 0.191 (SD 0.450) (P = 0.001). There was a negative correlation between the magnitude of ELISA reactivity and the time elapsed since the last appearance of foot warts. This apparent loss of seroreactivity over time may indicate that HPV 1 is usually eliminated from the host after infection or that inadequate levels of HPV 1 capsid antigen are produced during latent foot warts to maintain antibody levels.

Adolescent↗

Human leukocyte antigen class II alleles and natural history of HPV 2/27/57-induced common warts.

Epidemiological studies have demonstrated an association between HLA-DQB1*03 alleles and the risk of cervical cancer induced by human papillomavirus (HPV). As persistence of HPV infection is required for developing cervical cancer, we wanted to elucidate the role of HLA-class II allele polymorphisms in the persistence of common warts induced by HPV 2, HPV 27 or HPV 57. Therefore, we determined the distribution of HLA-DQA1, -DQB1, and -DRB1 alleles in 71 patients presenting with HPV 2/27/57-induced common warts which had persisted for at least 18 months as well as in 92 individuals who had never suffered from common warts or whose warts had healed in less than 18 months. Among patients with long-lasting warts, the carriership frequencies and allele frequencies of DQA1*0301, DQB1*0301, DRB1*07 and DRB1*09 were higher, and the allele frequencies of DQA1*0501, DQB1*0603, DRB1*01 and DRB1*03 were lower. Statistically significant differences (Bonferroni adjusted Fisher's exact test) were found for carriership frequency of DQA1*0301 (46.5 vs 21.7%, P = 0.013) and for carriership frequency (18.3 vs 1.1%, P = 0.0015) and allele frequency (12 vs 0.5%, P = 0.000013) of DQB1*0301. A greater proportion of patients with long-lasting warts than of subjects without persistent warts were homozygous at the DQA1 (14.1 vs 6.5%) and DQB1 (16.9 vs 8.6%) gene loci. These results suggest that the natural history of cutaneous HPV 2/27/57-induced common warts may be modulated by allele polymorphisms at the HLA-DQA1 and HLA-DQB1 gene loci.

Adult↗