genital warts
Absence of p53 mutations in benign and pre-malignant male genital lesions with over-expressed p53 protein.

Castren K, Vahakangas K, Heikkinen E, Ranki A.

Department of Pharmacology and Toxicology, University of Oulu, Finland.

Mutations of the tumor-suppressor gene p53 are common in epithelial tumors. Clonal mutations of p53 have been found in cervical and vulvar carcinomas negative for human papillomavirus (HPV), though at least in cervical cancer HPV infection and p53 mutations are not mutually exclusive. We have previously shown that about 40% of male genital warts and bowenoid papulosis lesions exhibit immunohistochemically detectable aberrant p53 protein, irrespective of the presence of HPV DNA. We studied p53 mutations in exons 4-8 with SSCP and sequencing in 13 male patients with 1 to 3 therapy-resistant genital warts or intra-epithelial neoplasias each and in 4 patients with penile squamous cell carcinoma. Thus, 13 genital warts, 6 bowenoid papulosis, 1 Queyrat's erythroplasia and 1 carcinoma in situ were studied. p53 protein was detected immunohistochemically, and HPV status was analyzed with DNA in situ hybridization and amplification of HPV-specific DNA. There was no correlation between p53 protein expression and HPV status. No mutations in exons 5-8 of the p53 gene were found in any of the lesions, and furthermore, no exon 4 mutations were found in lesions positive in p53 immunohistochemistry. In conclusion, overexpression of p53 does not indicate a p53 mutation in male genital warts, pre-malignant lesions or malignant squamous cell carcinomas. Our study thus suggests that p53 mutations are not important, or at least not early, events in male genital carcinogenesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9688297&dopt=Abstract genital wart


genital warts
Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A.

Thompson HS, Davies ML, Watts MJ, Mann AE, Holding FP, O'Neill T, Beech JT, Thompson SJ, Leesman GD, Ulrich JT.

Cantab Pharmaceuticals Research Ltd, Cambridge, UK.

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9796056&dopt=Abstract genital wart


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

Maw RD, Reitano M, Roy M.

Department of Genitourinary Medicine, Royal Victoria Hospital, Belfast, Northern Ireland, UK.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9819106&dopt=Abstract genital wart


genital warts
Imiquimod in clinical practice.

Edwards L.

Carolinas Medical Center, Charlotte, North Carolina, USA.

Applied topically, imiquimod induces the production of interferon-alpha plus other cytokines. Because intralesional interferon is effective in the treatment of condylomata acuminata (genital warts), topical imiquimod has also been investigated as a potential therapy for this condition. The dosing regimen found to best balance efficacy, side-effects and practicality is 5% imiquimod cream applied overnight by the patient three times weekly until warts clear, for up to 16 weeks. The largest double-blind trial to examine this protocol involved 311 patients with external anogenital warts who were randomized to use imiquimod 5% cream, imiquimod 1% cream or vehicle cream. Evaluation of all patients given medication at any time showed that 50% of those who received 5% imiquimod experienced clearing of all baseline warts, as compared to 21% of those who used 1% imiquimod and 11% of those treated with vehicle. Overall, 5% imiquimod treatment was significantly more effective than vehicle (P < 0.0001). Excluding patients who discontinued medication for reasons unrelated to therapy (such as moving out of town or poor compliance), 56% of those who received 5% imiquimod experienced complete clearing of baseline warts. Clearing also occurred in 27% of those who received imiquimod 1%. Recurrence of baseline warts occurred in 13% of patients whose warts cleared with 5% imiquimod. When applied overnight at home three times each week, topical imiquimod 5% cream is an effective therapy with acceptable side-effects. The recurrence rate is low and further studies to specifically compare recurrence rates are warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9842096&dopt=Abstract genital wart


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

Wardropper A, Woolley P.

Manchester Royal Infirmary, UK.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1286122&dopt=Abstract genital wart