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PubMed1997

Spontaneous or interferon-gamma-induced T-cell infiltration, HLA-DR and ICAM-1 expression in genitoanal warts are associated with TH1 or mixed TH1/TH2 cytokine mRNA expression profiles.

The purpose of the study was to investigate the cytokine gene expression patterns and immunohistochemical characteristics of genitoanal warts in order to obtain a clue as to the immunological mechanisms possibly relevant for wart regression or persistence. We analysed surgically removed warts from 11 patients, 2 of whom were immunosuppressed. Lesions of five of the nine otherwise healthy individuals were additionally treated with intralesional interferon-gamma (IFN gamma) prior to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1 expression on keratinocytes were found in two otherwise healthy patients and were intensified by intralesional IFN gamma in four of five patients. The mRNA expression patterns in seven of eight non-recurrent warts were compatible with a predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant warts of three patients (one healthy, two immunocompromised) histological signs of immunore-activity and TH1-like cytokine mRNA expression were not detected. In recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was repeatedly found suggesting a predominant TH2 response. In conclusion, immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM-1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine mRNA expression profile.

Adult↗
PubMed1994

Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts.

PURPOSE: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. PATIENTS AND METHODS: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. RESULTS: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. CONCLUSION: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient-administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease.

Adult↗
PubMed1989

Patient-applied podofilox for treatment of genital warts.

In a double-blind trial, 0.5% podofilox (podophyllotoxin) or placebo was applied by patients to their own genital warts in up to four treatment cycles. At some time during the study, 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free. At the end of the treatment, 73.6% of the original warts in podofilox treated patients were gone compared with only 8.3% of those in the placebo group (mean percentage of total original wart area was reduced by 82.3% compared with 4.2%). 82% of the treated warts in the podofilox group and 13% in the placebo group had resolved at 6 weeks. Recurrence was observed in 34% of the previously resolved warts. Consistent with this rate of recurrence, new warts developed in a third of the subjects in each group at sites remote from the treatment site. There were no systemic adverse reactions, although transient inflammation, erosion, pain, and burning were common.

Administration, Topical↗
PubMed2005

The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death.

Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine / threonine kinase and participates in a signaling complex that regulates both proliferation and apoptosis to ensure the proper size and shape of the fly. Human counterparts of this complex have been found to be frequently downregulated or mutated in cancers. WARTS, a human homolog of Wts, is also known as tumor suppressor and mitotic regulator, but its molecular implications in tumorigenesis are still obscure. Here, we show that WARTS binds via its C-terminus to the PDZ domain of a proapoptotic serine protease Omi / HtrA2. Depletion of WARTS inhibited Omi / HtrA2-mediated cell death, whereas overexpression of WARTS promoted this process. Furthermore, WARTS can enhance the protease activity of Omi / HtrA2 both in vivo and in vitro. Activation of Omi / HtrA2-mediated cell death is thus a potential mechanism for the tumor suppressive activity of WARTS.

Apoptosis↗
PubMed2000

Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor.

The mitotic apparatus plays a pivotal role in dividing cells to ensure each daughter cell receives a full set of chromosomes and complement of cytoplasm during mitosis. A human homologue of the Drosophila warts tumor suppressor, h-warts/LATS1, is an evolutionarily conserved serine/threonine kinase and a dynamic component of the mitotic apparatus. We have identified an interaction of h-warts/LATS1 with zyxin, a regulator of actin filament assembly. Zyxin is a component of focal adhesion, however, during mitosis a fraction of cytoplasmic-dispersed zyxin becomes associated with h-warts/LATS1 on the mitotic apparatus. We found that zyxin is phosphorylated specifically during mitosis, most likely by Cdc2 kinase, and that the phosphorylation regulates association with h-warts/LATS1. Furthermore, microinjection of truncated h-warts/LATS1 protein, including the zyxin-binding portion, interfered with localization of zyxin to mitotic apparatus, and the duration of mitosis of these injected cells was significantly longer than that of control cells. These findings suggest that h-warts/LATS1 and zyxin play a crucial role in controlling mitosis progression by forming a regulatory complex on mitotic apparatus.

Actins↗
PubMed1995

Use of human papillomavirus type 6 capsids to detect antibodies in people with genital warts.

Human papillomavirus (HPV) type 6 capsids were produced by recombinant vaccinia viruses and used in a capture ELISA to screen 901 human sera from three studies of genital HPVs. The highest seroprevalence was observed among subjects with recurrent genital warts. In a population-based case-control study of genital warts, 26 (58%) of 45 women with recurrent genital warts were seropositive compared with 19 (19%) of 101 control women with no history of genital warts (odds ratio, 6.5; 95% confidence interval, 3.0, 14.1). Among a cohort of pregnant women, 7 (88%) of 8 with recurrent warts were seropositive compared with 24 (30%) of 79 pregnant women with no such history. A significant association between seropositivity to HPV-6 capsids and the detection of HPV-6/11 DNA from genital specimens by polymerase chain reaction was also observed. Men with genital warts were less likely to be seropositive than were women with genital warts, and a positive association between the number of sex partners and seropositivity was observed among only the female university students.

Adult↗
PubMed1988

Risk factors in the development of cervical intraepithelial neoplasia in women with vulval warts.

Of 59 women referred with vulval warts whose cervices were assessed colposcopically for the presence of cervical intraepithelial neoplasia (CIN) before local treatment of the wart lesions, 17 had histologically proved CIN, 12 had histologically proved cervical wart virus infection, and 30 had abnormality on colposcopy or cytology. Seven of the 17 with CIN had no abnormality on cervical cytology. No differences in sexual behaviour, smoking habit, or oral contraceptive use were seen between women with CIN and those with no cervical abnormality. Viral DNA typing of the vulval lesions was carried out, but there were no differences in the distribution of viral types between the three different histological groups. Of the 30 women with no abnormality at the initial visit, 23 were followed up colposcopically and cytologically for one to two years. Three of them developed CIN after adequate treatment of the vulval lesions despite the absence of cervical abnormalities on colposcopy at the time of treatment. Studying the known factors linked with CIN failed to show why some women with vulval warts develop CIN, even after treatment of the warts, and others do not. The large number of false negative results on cervical cytology in our patients suggests that women presenting with vulval warts should be screened colposcopically in the first instance. Close follow up of women whose warts are treated and who are thought to have no cervical abnormality at that assessment is essential.

Adult↗
PubMed1992

A colposcopic case-control study of cervical squamous intraepithelial lesions in women with anogenital warts.

OBJECTIVE: To assess whether anogenital warts, present or past, are an indication for women to be referred for colposcopy. DESIGN: A case control study comparing patients with and without a history of anogenital warts. SETTING: A department of genitourinary medicine in West London. PATIENTS: 468 patients examined by colposcopy between January 1985 and December 1987 of whom 147 (31%) had abnormal cytology, 163 (35%) had anogenital warts and 158 (34%) had both. MAIN OUTCOME MEASURES: Colposcopic findings and histology of cervical biopsies compared with behavioural and disease variables. RESULTS: Human papillomavirus infection (HPVI) of the cervix showed no relationship with a life time history of vulval warts, or with the presence of anogenital warts on clinical examination, or with any parameter of sexual behaviour included in the study. Cervical intraepithelial neoplasia (CIN) was strongly associated with current IUCD usage (RR = 7.75) and coitarche under 16 years of age (RR = 3.72), but a history of vulval warts yielded a negative association (RR = 0.34), suggesting a protective effect. This relationship held true when cytological dyskaryosis was made the dependent variable (RR = 0.24). CONCLUSIONS: Anogenital warts are not a risk for subclinical cervical HPVI or for CIN and therefore not an indication for colposcopy.

Adult↗
PubMedDate not supplied

Treatment of anogenital warts in genitourinary clinics in England and Wales.

A questionnaire on the treatment of anogenital warts was sent to 150 consultants in genitourinary medicine, 78 (52%) were returned completed. A wide range of treatments were used; podophyllin was the commonest first line treatment of multiple penile (60.3%), perianal (57.7%) and vulval (61.5%) warts. Cryotherapy was a popular choice for intrameatal warts (65.3%), small numbers of vulval warts (33.3%) and as second line therapy for penile (35.9%) and perianal (33.3%) warts. Vaginal warts were treated with podophyllin (39.7%) or cryotherapy (29.5%). Various combinations of podophyllin, trichloroacetic acid and cryotherapy were used (2.6%-24.3%) although there is no evidence this offers benefit over single therapy. Podophyllin is frequently used despite side effects, a poor clearance rate and in vaginal warts, difficult access. Initial therapy with more time-consuming procedures such as cryotherapy or electrocautery may be of benefit to selected patients.

Condylomata Acuminata↗
PubMed2002

Information-giving to patients with genital warts at a genitourinary medicine clinic: a baseline assessment.

Aspects of information-giving to patients with a first episode of genital warts attending a large UK genitourinary medicine clinic on three or more occasions were assessed using a questionnaire survey employing correlational and between-groups analyses. The main outcomes measured were levels of, and interrelationships between, patients' perceptions of information received about genital warts, accuracy of knowledge, quality of interaction with clinic personnel, written information, patients' level of anxiety and demographic variables. Patients with genital warts have good basic knowledge about this condition, although understanding about several complex issues is poor. Educational level was positively correlated with accuracy of knowledge about genital warts. Although ease of communicative interaction with information-givers was positively correlated with perceived information given, no relationship was found between the latter and actual knowledge about genital warts. Anxiety levels and receiving written information were largely uncorrelated with accuracy of knowledge about genital warts. This study suggests that while patients' perception of information received may relate to more satisfactory interaction with information-givers, actual knowledge may be a more important measurable outcome. More interventional work is needed to determine how the information-giving process for genital warts can be optimized.

Adolescent↗
PubMed2006

[Clinical features and epidemiological survey of perianal warts in 72 males].

OBJECTIVE: To investigate the clinical features and epidemiological data of 72 cases of male perianal warts. METHODS: Seventy-two cases of perianal warts in our clinic dated from June, 2004 to April, 2006 were enrolled in the study, whose clinical information and epidemiological data were collected and analyzed. RESULTS: Perianal warts were most commonly seen in young and middle-aged men aged from 18 to 45, only 12.5% of whom had homosexual behaviors. Sauna was another predisposing factor of perianal warts in males in China (chi2 = 5.03, P < 0.05). Primary eruptions of the anus and rectum, like perianal pruritus, eczema, anus fissure, and haemorrhoids, often impaired the local integrity of skin/mucosa. Classical condyloma acuminate was found in 61 (84.72%) of patients, who were susceptive to the infections of HPV 6/11, and were flat condylomas related to HPV16/18. Cryotherapy was believed to be one of the most efficient therapeutic choices for flat perianal warts. Suppression of cellular immune response was identified in the patients by comparison between the subgroups of peripheral T cells and the normal control. CONCLUSION: Sauna is an essential predisposing factor of perianal warts in males, while anus sexual intercourse is not the main route of HPV infection. Classical condylomata acuminate constitute the majority of the eruptions, and flat condylomata come next. The study also provides some useful data for understanding the clinical and epidemiological features of perianal warts in Chinese males for the sake of prevention and treatment of the disease.

Adolescent↗
PubMed1980

Hormonal control of head-wart development in the snail, Euhadra peliomphala.

The terrestrial snail, Euhadra peliomphala, has a peculiar organ between the optic tentacles named the head-wart, which releases a sex pheromone just before courtship. The development of the head-wart was closely correlated with the sexual maturity of the snail. Castration led to the atrophy of the head-wart. Subsequent injection of hermaphrodite gland homogenate into the body cavity of castrated individuals induced the development of the head-wart. The peripheral regions of the acini in the hermaphrodite gland showed a positive reaction for 3 beta-hydroxy steroid dehydrogenase. Furthermore, preliminary radioimmunoassay also showed that the hermaphrodite gland of the snail contained testosterone and estradiol. When the immature head-wart was cultured for 10 days in a medium containing testosterone and estradiol respectively, development of the head-wart was found only in medium containing testosterone. From these results, it is concluded that head-wart development in the snail, Euhadra peliomphala, is under direct control from the hermaphrodite gland, probably by means of testosterone.

Animals↗
PubMed1993

Histologic, pharmacologic, and immunocytochemical effects of injection of bleomycin into viral warts.

BACKGROUND: The plasma concentration of bleomycin after injection of bleomycin into warts is unknown, as is the long-term stability of bleomycin solution. OBJECTIVE: Our purpose was to measure plasma bleomycin concentration after injection of bleomycin into warts, to relate histologic and immunocytochemical changes in warts to possible mechanisms of action of bleomycin, and to asses the long-term stability of stored frozen bleomycin solution. METHODS: One milligram of bleomycin was injected into warts on the hands of seven men. Blood samples were taken 15 to 120 minutes after injection, and plasma bleomycin was measured by radioimmunoassay. Warts were removed 2 hours and 48 hours after treatment and studied histologically by light microscopy and for the presence of bleomycin by immunocytochemistry. The bleomycin concentration in 8 aliquots of solution stored at -20 degrees C for varying periods was measured by radioimmunoassay. RESULTS: Peak levels of bleomycin of 7 to 113 ng/ml were reached by 45 minutes after injection. Plasma bleomycin exposure ranged from 515 to 5137 ng/ml/min between 15 and 120 minutes after injection. The most pronounced histologic changes at 48 hours were individual keratinocyte apoptosis throughout the epidermis merging into areas of complete epidermal necrosis, diffuse neutrophil accumulation, and microabscess formation at the granular layer. Immunocytochemistry demonstrated tissue-fixed bleomycin in all levels of the epidermis except the basal layer and most prominently in the granular layer. Bleomycin in solution stored for up to 27 months at -20 degrees C in glass showed no significant loss of immunoreactivity. CONCLUSION: The use of bleomycin for the treatment of warts results in significant systemic drug exposure; thus it would be prudent to exclude pregnancy before treating women of child-bearing age. Bleomycin probably has a direct toxic effect on keratinocytes. Dilute bleomycin solution stored at -20 degrees C in glass is stable.

Bleomycin↗
PubMed2000

A randomized trial of distant healing for skin warts.

PURPOSE: Distant healing, a treatment that is transmitted by a healer to a patient at another location, is widely used, although good scientific evidence of its efficacy is sparse. This trial was aimed at assessing the efficacy of one form of distant healing on common skin warts. SUBJECTS AND METHODS: A total of 84 patients with warts were randomly assigned either to a group that received 6 weeks of distant healing by one of 10 experienced healers or to a control group that received a similar preliminary assessment but no distant healing. The primary outcomes were the number of warts and their mean size at the end of the treatment period. Secondary outcomes were the change in Hospital Anxiety and Depression Scale and patients' subjective experiences. Both the patients and the evaluator were blinded to group assignment. RESULTS: The baseline characteristics of the patients were similar in the distant healing (n = 41) and control groups (n = 43). The mean number and size of warts per person did not change significantly during the study. The number of warts increased by 0.2 in the healing group and decreased by 1.1 in the control group (difference [healing to control] = -1.3; 95% confidence interval = -1.0 to 3.6, P = 0.25). Six patients in the distant healing group and 8 in the control group reported a subjective improvement (P = 0.63). There were no significant between-group differences in the depression and anxiety scores. CONCLUSION: Distant healing from experienced healers had no effect on the number or size of patients' warts.

Adult↗
PubMed1975

Regression of warts. An immunological study.

Altogether 173 patients with warts were under observation for at least 3 and in most cases 6 months. In 80% of the patients wart-virus antibodies were present and could be measured by immunodiffusion (I.D.) and in 20% also by complement-fixation (C.F.) techniques. The mean duration of the warts in patients with C.F. antibodies was 0-6 years and in the others 1-9 years. The occurence of C.F. antibodies (IgG) was associated with rapid healing; 75% of these patients were cured during the first 2 months of the observation period. In contrast, of the patients with antibodies measurable only by the I.D. technique (IgM and/or low titres of IgG), only 16% were cured during the first 2 months and they had a fairly constant cure-rate (approximately 9% per month) during the 6 months' observation period. The results indicate that the cure of warts is partly connected with immunological phenomena, especially with the presence of C.F. antibodies. In other cases wart regression may be mainly a non-immune process, perhaps due to a limited lifespan of wart cells.

Adolescent↗
PubMed2001

Cryotherapy of viral warts: a sustained 10-s freeze is more effective than the traditional method.

BACKGROUND: Cryotherapy is a standard treatment for viral warts. Although textbooks recommend treating until there is a halo of ice around the wart (traditional freeze), many authors advocate more aggressive cryotherapy. There are no previously published studies assessing the efficacy of longer freezing times. OBJECTIVES: To compare the efficacy of the traditional freeze and a sustained 10-s freeze in the treatment of common viral warts with liquid nitrogen. METHODS: Patients attending a dedicated wart clinic were randomized to receive either a traditional freeze or a 10-s sustained freeze with liquid nitrogen delivered by a spray gun. Two hundred patients were recruited, 100 in each group. RESULTS: After five treatments, 49 patients in the 10-s freeze group were clear of warts (64% of non-defaulters) as compared with 31 (39%) of those in the traditional freeze group (chi2 = 6.7; P = 0.009). Seventy-four patients in the 10-s freeze group as compared with 59 in the traditional freeze group had either improved or cleared after five treatments (chi2 = 5.0; P = 0.02). Morbidity was significantly greater in the 10-s freeze group. Sixty-four patients suffered pain or blistering as compared with 44 in the traditional freeze group (chi2 = 10.8; P = 0.0045). Five patients were withdrawn from the 10-s freeze group because of pain as compared with one patient in the traditional freeze group. CONCLUSIONS: A 10-s sustained freeze is more effective in the cryotherapy of viral warts but carries a significantly greater morbidity in terms of pain and blistering.

Adolescent↗
PubMed2000

Treatment of viral warts with cimetidine: an open-label study.

The immunomodulatory actions of cimetidine, an H2-receptor antagonist, and its use in the treatment of viral warts has been described previously but its effectiveness is still debated. We report the results in 47 patients with multiple, nongenital viral warts who were treated with oral cimetidine in a 3-month open-label study. The drug was generally well tolerated and 87% of children and 68% of adults improved with treatment. Follow-up data in 65% of the patients showed that there had been no recurrence in the majority of those whose warts had cleared completely during treatment, whereas warts tended to persist or recur in those who had stopped treatment before all the warts had resolved. Our data suggests that cimetidine may be helpful in the treatment of viral warts in both adults and children and supports the need for a randomized controlled trial.

Adjuvants, Immunologic↗
PubMed2003

Successful treatment of butcher's warts with imiquimod 5% cream.

A unique correlation has been shown to exist between frequent occupational handling of raw meat and development of warts on the hands, leading to the designation of 'butcher's warts'. Numerous treatments are available for warts including cryotherapy, laser therapy and surgical excision. We present a case of a 31-year-old-butcher with a 4-year history of warts on his fingers. Imiquimod 5% cream was applied once daily to the warts for 3 months. Clinical improvement was noted after 1 month, with regression of the warts experienced after 3 months. During 12 months of follow-up, no recurrent lesions were observed.

Adjuvants, Immunologic↗