Patient assessment of anogenital warts and the success of treatment with home applied therapy.

Home treatment with podophyllotoxin or imiquimod are commonly prescribed therapies for anogenital warts. It is important to ascertain if patients are locating all lesions for treatment and if they know when they are clear of them. We set out to assess patients' ability to determine the number and location of their genital warts and compare their observation with that of their examining doctor or nurse. Following instruction on the use of home treatment and being given an instruction leaflet patients were reviewed in four weeks' time. One hundred and fifty-five patients enrolled in the study--31% (48) male, 69% (107) female. At initial assessment 62.5% (30) of male patients and 59.8% (64) of female patients underestimated the extent of their disease: 10.5% (5) of male patients and 10.3% (11) of female patients overestimated their disease burden with some mistaking skin tags for genital warts. At review 29.4% (5) of male patients and 44.4% (20) of female patients still underestimated the extent of their infection. Patients undertaking home treatment for warts not only need detailed instruction on its use but should be reviewed to assess the success of treatment.

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males.

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.

Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial.

Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.

Genital schistosomiasis.

Schistosomiasis is the most serious helminthic infection in the United Kingdom. Female genital schistosomiasis affects 9-13 million women worldwide, mainly in areas where Schistosoma haematobium is endemic. With increasing tourism to these areas, this diagnosis is being encountered more frequently in the West. We present 2 cases of vulval schistosomiasis that were presented to our department in 1999 and 2000.

An international survey of patients with genital warts: perceptions regarding treatment and impact on lifestyle.

Our aim was to determine country-specific attitudes and perceptions of patients with genital warts and to understand the psychosexual impact of the disease and its treatment. We used a standardized discussion guide to interview patients with genital warts in Canada, France, Germany, the UK, and the USA about their perceptions and concerns regarding the diagnosis, treatment, and psychosexual impact of the disease. Interviews were conducted in person and lasted approximately 30 min. The study group included 80 men and 86 women with genital warts. Forty-seven per cent were currently undergoing treatment. Overall, 49% of the men had first consulted a general or family practitioner, and 52% of the women had first consulted a gynaecologist. Although all the patients eventually consulted a physician about their warts, one-third delayed seeing a doctor because they thought the condition would resolve on its own or that the problem was not serious. Most patients reported that treatment was associated with pain, discomfort, and embarrassment. Sixty per cent of patients experienced a recurrence after initial clearance with treatment. More than 80% stated that they had had little or no involvement in the selection of treatment. Globally, 52% of men and 61% of women were 'quite concerned' or 'very concerned' about having genital warts, although there were significant variations by country. Approximately two-thirds of patients had made lifestyle changes regarding sexual relationships. In addition, two-thirds believed that there were risks associated with having genital warts; the most common risk identified was a link to cancer (cervical and unspecified). A high level of anxiety is associated with the diagnosis and treatment of genital warts. Patients with genital warts require understanding and an acknowledgement of their concerns. A better understanding of the psychosexual aspect of the disease by health-care providers is pivotal to effective disease management and patient counselling.

Treatment of anogenital warts.

The treatment of anogenital warts has long been unsatisfactory, with high treatment failure rates and relapse rates. It would seem that a good cell-mediated immune response is important for successful treatment, and the development of immune response modifiers such as Imiquimod give hope for an improved outcome for many patients.

A pilot study to investigate the treatment of anogenital warts with Topical Lithium Succinate cream (8% lithium succinate, 0.05% zinc sulphate).

The incidence of anogenital warts (condyloma acuminatum) is rapidly increasing while there is still no totally satisfactory treatment available. In light of the emphasis of experimental approaches toward the prevention of viral replication and evidence of the antiviral action of lithium salts it was proposed to investigate the efficacy of Topical Lithium Succinate cream (LSC) in the treatment of anogenital warts. A total of 101 patients (42 women, 59 men) were randomized to receive either active or placebo treatment for a period of 4 weeks. Assessment of the number, location, size and area of coverage of the warts was made by the clinician at baseline, weeks 2, 4, 6 and 12. Compliance to the study protocol following cessation of treatment at week 4 was extremely poor. The high drop-out rate after this was felt to invalidate data collected after that point. It was therefore decided that the analysis should concentrate on the treatment period. Of 101 patients entering the trial 51 received active (30 male and 21 female) and 50 received placebo (29 male, 21 female). The primary efficacy variable was percentage change from baseline in the overall coverage of lesions. Over all patients LSC treatment resulted in a reduction of 42% (P<0.02) in the overall coverage of lesions. Separate analyses for male and female patients showed that for males there was a highly significant reduction in the coverage of lesions of 65% (P<0.02). However for females the reduction of 11% was not significant. A possible explanation for this difference between the sexes is that as many of the lesions in the female patients were internal therefore this could lead to difficulty in both application of the cream, and subsequent lesion assessment.

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland.

We have sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype B. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis we estimate the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic.

Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts.

OBJECTIVE: To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and/or perianal warts produces a 30% or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy. DESIGN: Randomised, triple-blind, placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery. SETTING: International, multicentre study in 10 genitourinary medicine clinics. PATIENTS: Two hundred and fifty patients with anogenital warts. MAIN OUTCOME MEASURES: Lasting response at week 38. RESULTS: Standard efficacy analysis at week 38 showed a lasting response in 51% (35/68) of 3 MIU interferon-treated patients, 48% (30/63) of 1 MIU interferon-treated patients and 43% (29/67) of placebo-treated patients. CONCLUSIONS: With the doses and regime described, treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy.

Detection of human papilloma virus DNA sequences in oral squamous cell papillomas by the polymerase chain reaction.

Nineteen clinically diagnosed, and histologically confirmed oral squamous cell papillomas were analyzed for the presence of human papilloma virus DNA sequence by the highly sensitive polymerase chain reaction technique, followed by dot blot hybridization of the polymerase chain reaction product with digoxigenin-labeled, type-specific oligonucleotide probes for human papilloma virus DNA types 6, 11, 16, and 18. Human papilloma virus DNA types 6 and 11 were identified in 68% of these oral lesions, which raises the possibility of an etiologic role for human papilloma virus in the pathogenesis of oral squamous cell papillomas.

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES: The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN: Randomised, double-blind parallel group study. SETTING: Multicentre study in six genitourinary clinics within the U.K. PATIENTS: One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES: Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS: At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS: At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.

The role of early colposcopy in the management of females with first episode anogenital warts.

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically-confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear (P < 0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

Detection of human papillomavirus by the polymerase chain reaction in histologically normal penile skin adjacent to penile warts.

BACKGROUND AND OBJECTIVES: Anogenital warts frequently recur following ablative treatment, and in the female, has been attributed to the presence of latent HPV infection outside the treatment margins. GOAL OF THIS STUDY: To determine whether HPV DNA sequences were detected by PCR in histologically normal penile skin adjacent to penile warts and to correlate recurrence of warts following surgical ablation to the presence of HPV DNA in histologically normal penile skin. STUDY DESIGN: Prospective cohort study of 25 heterosexual men with penile warts. Biopsies of clinically healthy penile skin 1 cm from the nearest penile lesion (wart with/without surrounding acetowhite changes) were processed for histology and HPV DNA analysis. The penile wart was processed for HPV DNA analysis only. Recurrence of penile warts was correlated to HPV status of adjacent histologically normal penile skin using Fisher's exact test (FET). RESULTS: Sequences homologous to HPV DNA were detected in 77% of biopsies of histologically normal penile skin. Agreement in HPV DNA type between penile wart and the adjacent histologically normal penile skin was only 30%. Recurrence of warts was noted in 46% of men by 16 weeks, and was not predicted by the detection of HPV DNA in the adjacent histologically normal penile skin (P = 0.16, FET). CONCLUSIONS: These findings suggest that extending the treatment margins 1 cm beyond the visible lesion is ineffective in eradicating the virus and preventing recurrence of warts.

Anogenital warts in children.

Fourteen children presenting with anogenital (AG) warts and their close family members were studied; 28.6 and 8.3% of presenting children and other child household members, respectively, had non-genital cutaneous warts; 42.8% of children with AG warts had one or more adult household member with common hand warts. Fifty per cent of all mothers had subclinical cervical papilloma virus (PV) infection; only one male adult had subclinical PV infection of the penis without concurrent AG warts. Of the children with AG warts 42.8% had one or more adult household member with AG warts. Human papilloma virus (HPV) deoxyribonucleic acid (DNA), type 6/11 most frequently, was detected in 38.5% AG wart biopsies from children, and 67% AG wart biopsies from adults. HPV 31/33/35 was detected in 28.5% of cervical preneoplasias and type 6/11 in the one case of subclinical PV infection of the penile shaft. Detection of HPV types 6/11, 16/18, or 31/33/35 in AG warts in children was significantly associated with vertical (from an HPV-infected maternal birth canal during vaginal delivery) or sexual transmission of these warts (Fisher exact probability P = 0.031).

Human papillomavirus DNA detection in primary anogenital warts and cervical low-grade intraepithelial neoplasias in adults by in situ hybridization.

In this study, 58 consecutive patients with primary anogenital warts were selected from patients attending a genitourinary clinic. Patients were grouped on the basis of clinical lesion site, i.e. patients with genital warts only, patients with perianal or anal canal warts only, and patients with concurrent perianal and genital warts. Of these patients, 38% of the men (12/31) and 33.3% of the women (9/27) had other anogenital infections, such as nonspecific urethritis (NSU) or nonspecific genital infection, which were the most common. Of the patients who had perianal warts, 37% of the men (7/19) and 25% of the women (4/16) also had warts in the anal canal. Of the women who had anogenital warts, 63% (17/27) had concurrent subclinical low-grade cervical intraepithelial neoplasia (CIN) lesions. Human papilloma virus (HPV) DNA (either 6 or 11, 16 or 18, or 31 or 33 or 35) was detected in 53.3% (40/75) of the anogenital wart biopsy samples, and in 35.2% (6/17) of the low-grade CIN lesions. HPV types 6 or 11 were the most common types in anogenital warts (45.3%); and in CIN lesions HPV types 6 or 11 and 16 or 18 were found with equal frequency (17.6% each). There were no significant differences in HPV types between patients with genital warts and patients with perianal and anal canal warts. Anogenital infection with HPV is multicentric; external anogenital warts and subclinical CIN lesions often exist concurrently. The low prevalence of HPV DNA detected in anogenital warts and CIN biopsy samples may be due to insensitivity of the in situ hybridization technique used in this study.

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.