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A comparison of interferon alfa-2a and podophyllin in the treatment of primary condylomata acuminata. The Condylomata International Collaborative Study Group.

OBJECTIVES: to compare the response to treatment and recurrence rate of condylomata accuminata using subcutaneous injection of interferon alfa 2a 1.5 million units three times weekly for four weeks, or podophyllin resin 25% applied to lesions twice weekly for up to six weeks. DESIGN: Randomised open study. SETTING: Multicentre European study in genitourinary medicine, dermatovenereology, and gynaecology departments. PATIENTS: 87 males and 67 females with condylomata acuminata for less than six months and no history of previous treatment. MAIN OUTCOME MEASURES: Complete clearance of lesions and evidence of recurrence at three months and nine months after treatment commenced. RESULTS: A complete response was achieved at three months in 15 of 64 (23%) in the interferon treated group, and 31 of 69 (45%) in the podophyllin treated group (p = 0.003). At nine months 10 of 13 patients in the interferon group and 22 of 30 patients in the podophyllin group remained completely clear of lesions.

Administration, Topical

Initial experience with combined interferon-alpha 2B and carbon dioxide laser for the treatment of condylomata acuminata.

The incidence of condylomata acuminata, a common sexually transmitted disease caused by certain types of human papillomaviruses, is increasing rapidly and treatment regimens presently are not consistently effective. One of the more popular and effective modes of treatment has been laser therapy. Because of the relatively high recurrence rate of condylomata acuminata with laser treatment alone and because laser treatment in some patients with confluent acetowhite lesions would render cosmetically unacceptable results in the entire area were treated, we believed that it was reasonable to use intralesional pretreatment. We present our preliminary data on 14 consecutive patients with the clinical diagnosis of condylomata acuminata who were treated with the combination of carbon dioxide laser and intralesional interferon-alpha 2B. We found the treatment regimen to be effective in decreasing the recurrence rate compared to laser treatment alone and it was well tolerated with only transient side effects in a minority of patients. We are encouraged by our result and have recently begun a randomized double-blind prospective study to provide more conclusive information regarding this treatment combination.

Adolescent

Rearrangements of the upstream regulatory region of human papillomavirus type 6 can be found in both Buschke-Löwenstein tumours and in condylomata acuminata.

Clinically malignant Buschke-Löwenstein tumours and benign condylomata acuminata are caused by human papillomaviruses (HPVs), predominantly HPV-6 and -11. In some cases, the HPV-6 genomes found in Buschke-Löwenstein tumours and in verrucous carcinomas differ from HPV-6b isolated from a benign genital wart, by rearrangements of the upstream regulatory region (URR). To evaluate the frequency and role of mutations of the URR of HPV-6 we analysed 42 condylomata acuminata and four Buschke-Löwenstein tumours by the polymerase chain reaction and restriction enzyme cleavage. Using only four different restriction enzymes we could demonstrate four distinct restriction patterns, indicating that naturally occurring HPV-6 isolates display a high degree of DNA polymorphism within the URR. One Buschke-Löwenstein tumour and two condylomata acuminata yielded rearranged URRs with DNA duplications. All three lesions harboured multiple HPV-6 variants, suggesting that cellular or environmental factors facilitate the development of rearrangements. Therefore, rearrangements of the URR may represent only secondary events in condylomata acuminata and Buschke-Löwenstein tumours which do not necessarily confer a higher malignant potential to the infected cell.

Base Sequence

[Cryosurgery of condylomata acuminata gigantea--a contribution to therapy].

Two cases of condylomata acuminata gigantea treated with cryosurgery are described. A clinical and histologic differentiation from Buschke-Loewenstein's tumours, sex-specific differences, possible malignant transformations and differential diagnostic diseases are described and references are made to confusions with condyloma-like, primary carcinomas. Compared to conservative surgical treatment of condylomata acuminata gigantea, cryosurgery offers the advantage of rapid necrosis of the condylomata which are repelled without any further surgical intervention and heal without scars. Therefore we consider cryosurgery a more refined technique in treatment of condylomata acuminata gigantea. In extensive involvement, however, cryosurgical measures must be repeated.

Adult

[Clomiphene citrate ointment in the local treatment of condylomata acuminata].

The hypothesis underlying local treatment of Condylomata acuminata with clomiphene citrate is based on the assumption that susceptibility to this disease in women depends on the relative amount of oestrogen receptors in the affected, as opposed to the unaffected areas. We postulate blockade of these skin receptors after local application of clomiphene citrate ointment. A pilot study was conducted in 15 patients aged 20-33 with Condylomata acuminata. After only 2 months a complete remission was recorded in 12 patients (= 80%).

Administration, Topical

Dinitrochlorobenzene treatment of condylomata acuminata.

Fifteen patients with treatment-resistant condylomata acuminata have been treated by application of Dinitrochlorobenzene (DNCB). The agent was applied weekly as a 0.5 or 1% solution in acetone for a period of 6 to 8 weeks. Patients were sensitised 15 days before the onset of treatment by applying a 2% DNCB solution on the right arm in a quantity of 0.15 ml. In one patient treatment had to be stopped because of local irritation and one discontinued treatment. In the other 13 patients all lesions cleared completely. Patients were followed up for a year and no recurrence has appeared as yet. DNCB seems to be useful agent for treatment-resistant condylomata acuminata and justifies further clinical trials.

Adult

Use of human papillomavirus type 11 virions in an ELISA to detect specific antibodies in humans with condylomata acuminata.

Human papillomavirus types 6 and 11 (HPV-6 and HPV-11) are the major aetiological agents of condylomata acuminata. Serological studies of this disease have been difficult to perform and interpret because native, type-specific antigens have not been available. In particular, since these viruses have not been propagated in vitro and sufficient quantities of virions are not present in lesions, virus particles have been difficult to obtain. In the present study, we used HPV-11 particles, obtained from human tumours produced in athymic mice, as antigen in an ELISA to compare antibody responses between 46 patients with biopsyproven condylomata acuminata and 44 controls. The median [interquartile range] of the absorbance values for the condylomata acuminata and the control groups were respectively 0.324 [0.183, 1.029] and 0.118 [0.047, 0.286] (P = 0.0001). Thirty-three per cent of the absorbance values in the condylomata acuminata group were higher than any of those of the control group. Sera from patients whose biopsies contained the papillomavirus common antigen were more reactive than sera from patients whose biopsies did not contain it (P = 0.0014). This study demonstrates the presence of specific antibodies directed at native HPV-11 viral particles in the sera of patients with condylomata acuminata, and describes a test which can be used in future serological studies of this common sexually transmitted disease.

Adult

[Postoperative adjuvant therapy with interferon alfa-2B following laser surgery of condylomata acuminata].

Sexually transmitted diseases caused by human papilloma viruses, such as condylomata acuminata, are increasing in incidence and are often difficult to treat because of their tendency to recur. Many reports in the literature document the usefulness of interferons topically or systemically in these diseases. A randomized study was conducted to evaluate interferon Alfa-2b (Intron A) as adjuvant therapy following CO2 laser surgery of condylomata acuminata. A low-dose regimen was administered (two courses with 1 million I.U. s.c. daily for 6 days with a 2-week interval between the courses) and had hardly any side-effects. The recurrence rate in the therapy group was significantly reduced (42% vs 81%), so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed.

Adolescent

[Adjuvant systemic interferon alpha-2B treatment in treatment refractory anogenital Condylomata acuminata].

Despite different treatment modalities, resistance to treatment is observed in 4-15% of patients with anogenital condylomata acuminata. A total of 16 patients with resistant condylomata acuminata or extended infection affecting an area of more than 6 cm2 were treated with a prospectively defined therapy entailing laser treatment and adjuvant systemic interferon-alpha 2B (3 x 1 MU/day for 7 days). Of the 16 patients, 13 (81%) were in complete remission after an 8-month period of follow up. The typical side-effects of interferon were attenuated in 80% of cases by simultaneous paracetamol (3 x 500 mg/day). The combination of laser treatment and adjuvant systemic interferon-alpha 2B seems to be highly effective in the treatment of resistant or extended condylomata acuminata. At present, these results are being tested for significance in a prospectively randomized study.

Adult

[Anal condylomata acuminata in HIV positive patients].

Since July 1986 we started with following all patients with condylomata acuminata including HIV-testing and human papilloma virus (HPV) identification by DNA-DNA-hybridisation (southern blot). Seventy patients are included, 39 of them are seropositive. The ratio male to female is 59 to 11, in seropositives 35 to 4, in negatives 24 to 7. The average age is 28 and 31 years respectively. The number of homosexuals and junkies is significantly higher in seropositives. Seventeen patients are in HIV-stage II, 11 in stage III and 10 in stage IV according to CDC-classification. Characteristic for the seropositives was an extensive growth on the rectal mucosa and the very rapid growth of initially subtotally resected lesions in order to prevent stenosis. Sixty-five patients were treated by one stage radical operation with electrocauter. Surprisingly recurrency is more frequent in seronegatives, however, the lesion is much smaller in this group. A hypothesis to explain this observation is brought forward. Postoperative complications occurred only in HIV-stages III and IV. We therefore recommend single shot antibiotic prophylaxis in these patients. The HPV-identification showed no malignancy associated HPV-types in both groups but a higher incidence of HPV 11 in higher HIV-stages which we cannot explain. We conclude from our series that, if operation is indicated, one stage radical electrocoagulation of condylomata acuminata is a necessary procedure in seropositive patients and a save one in negative patients but antibiotic prophylaxis should be given in stage III and IV. Anal condylomata acuminata are a hint for possible HIV-positivity.

Adolescent

Carcinoma of the vulva arising in condylomata acuminata.

A case of carcinoma of the vulva arising in condylomata acuminata is presented. The patient was much younger than is classically reported for carcinoma of the vulva. The vulvar growth was first noted during pregnancy, and it continued to grow and enlarge following delivery. Malignancy appeared to develop after a relatively short time. It is sometimes difficult to distinguish vulvar condylomata acuminata from carcinoma from clinical evidence alone. It is, therefore, mandatory in doubtful cases to take multiple biopsies from the lesion before treatment is instituted.

Adult

Treatment failure of genital condylomata acuminata in women: role of the male sexual partner.

The male sexual partners of women with genital condylomata acuminata are thought to be carriers of human papillomaviruses. It is therefore often recommended that both sexual partners be treated. We studied 360 women with genital warts to test the hypothesis that when the male partners of women with condylomata acuminata are treated, the treatment failure rate decreases. The male sexual partners of 180 of these women were examined and, if indicated, treated (treatment group). The 180 remaining male sexual partners were neither examined nor treated (control group). One hundred twenty-two (68%) men in the treatment group had human papillomavirus-associated lesions. The treatment failure rate of women was 16.7% in the treatment group and 18.9% in the control group. The difference is not statistically significant (p greater than 0.05). The results of this study do not support the hypothesis that the treatment failure rate of women with condylomata acuminata decreases if their male sexual partners are also treated.

Adolescent

Treatment of extensive vulvar condylomata acuminata with topical 5-fluorouracil.

Forty-nine nonpregnant women with extensive condylomata acuminata of the vulva were studied to evaluate the effectiveness of topical 5-fluorouracil (5-FU) for treating vulvar condylomata and to compare the results of continuous use with periodic use of the medication. Patients using the continuous regimen were instructed to apply 5% 5-FU cream to the vulva each night for 6 weeks or until a brisk inflammatory reaction occurred. The periodic regimen consisted of applying 5-FU cream on 2 consecutive nights per week for 10 week. Thirty-five patients (71%) responded to 5-FU treatment (20 complete responses, 41%; 15 partial responses, 30%). Fourteen patients (29%) did not respond. The response rates observed in 19 patients using the continuous regimen (eight complete responses, five partial responses, and six treatment failures) were not significantly different from the response rates obtained in 30 patients with the periodic regimen (12 complete responses, 10 partial responses, and eight treatment failures; P greater than .05, chi-squared test). The periodic regimen caused fewer side effects than the continuous regimen. I conclude that topical 5-FU is effective for treatment of vulvar condylomata acuminata and that periodic applications are preferable to continuous applications.

Administration, Topical

Cryotherapy in the treatment of condylomata acuminata: a controlled study of 64 patients.

A clinical controlled study is presented for the treatment of condylomata acuminata with cryotherapy in 64 patients. Condylomata resolved in 83% within 4 weeks and 96% after 6 weeks by using cryotherapy. The results were significantly better compared with the control group of 70 patients (13% and 45% after 4 weeks and 6 weeks, respectively). Other therapeutic modalities are reviewed. Cryotherapy is an elegant and effective method for the treatment of condylomata acuminata without discomfort to the patient.

Condylomata Acuminata

Condylomata acuminata of the bladder: a rare cause of intraluminal-filling defects.

Condylomata acuminata is a sexually transmitted disease commonly affecting the mucocutaneous surfaces of the anogenital region. Extension to the bladder is exceedingly rare. We present a case of condylomata acuminata causing intraluminal-filling defects of the bladder in a patient being evaluated for chronic urinary tract infections.

Adult

Condylomata acuminata and risk of cancer: an epidemiological study.

OBJECTIVE: To determine whether patients with condylomata acuminata have an increased risk of developing cancer. DESIGN: Prospective cohort study on patients diagnosed as having condylomata acuminata. The number of malignant tumours in the cohort was compared with national incidences obtained from the Swedish Cancer Registry. SETTING: Dermatology department of the Karolinska Hospital, Stockholm, Sweden. SUBJECTS: 3260 patients (2549 males and 711 females, median (range) age 23 (1-80) years) seen during 1969-84, with a mean follow up of 7.8 years. MAIN OUTCOME MEASURES: Number of malignant tumours observed in the cohort during the study period and expected number from national incidence. RESULTS: There were 27 malignancies in the study group. There was no significant increase genital cancer in females compared with the national incidence. Only one patient had invasive cervical cancer (relative risk = 1.8; 95% confidence interval 0 to 10.1). Seventeen women had cervical carcinoma in situ (1.5; 0.9 to 2.5) compared with an expected number of 11.5; this increase was not significant. For males 22 cancers were observed at all sites (1.6; 1.0 to 2.5). The number of genitourinary cancers observed in males was almost three times higher than expected (2.6; 1.2 to 5.0). CONCLUSION: The results indicate that the risk of developing cervical carcinoma in situ or invasive cervical cancer after a genital human papillomavirus infection is less than previously thought. The implications of increase in the genitourinary malignancies in males are uncertain.

Adult

Condylomata acuminata in the pediatric population.

The incidence of condylomata acuminata infection has shown a steady increase for adults and children in recent years. With the discovery that the viral agents of this disease are potentially neoplastic, a disorder that was once considered a nuisance is now taking on new-found importance and concern. Furthermore, the knowledge that these lesions are often sexually transmitted and the ever-increasing concern over child abuse have combined to make the recognition and treatment of this disease in the pediatric population of even greater significance. Depending on location, podophyllum resin (podophyllin) is the initial therapy of choice. Available studies indicate a cure rate ranging from 22% to 98% depending on location of the warts, frequency of treatment, patient compliance, and freshness of the podophyllum resin preparation. Cure rates of 91% to 97% have been reported with cryotherapy and laser photocoagulation. Eradication of the viral agent and long-term follow-up are important.

Adolescent

Human papillomavirus detection in cervical dysplasias or neoplasias and in condylomata acuminata by in situ hybridization with biotinylated DNA probes.

Specimens from cervical dysplasias or carcinomas and genital condylomata acuminata were retrospectively analysed by in situ hybridization (ISH) with biotinylated DNA probes for human papillomavirus (HPV) types 6, 11, 16 and 18. In the control group no case was positive for HPV DNA. In mild/moderate dysplasias, 4 cases (14%) were positive for HPV 6 or 11 and 2 cases (7%), for HPV 16. In the severe dysplasia/in situ carcinoma group, 9 cases (31%) showed presence of DNA of HPV types 16 or 18. Six invasive carcinomas (20%) were positive for HPV type 16 or 18. Among condylomata acuminata, 22 cases (73%) were positive for HPV types 6 or 11. In all ISH-positive cases only one viral type was detected. No correlation between HPV DNA positivity and histological findings of HPV infection was observed. Although less sensitive than some other molecular biology techniques, in situ hybridization with biotinylated DNA probes proved to be simple and useful for detecting and typing HPV in samples routinely received for histopathological analysis.

Biotin