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Treatment of Urethral Condylomata Acuminata or Flat Condylomata with Interferon-α2a
0022-5347 /94/J.526-2011$03.00/0 Vol. 152,
THE JOURNAL OF UROLOGY Copyright © 1994 by AMERICAN UROLOGICAL ASSOCIATION, INC.
TREATMENT OF URETHRAL CONDYLOMATA ACUMINATA OR FLAT CONDYLOMATA WITH INTERFERON-a2a E. CARDAMAKIS, 1.-G. KOTOULAS, K. METALINOS, H. MANTOUVALOS, K. RELAKIS, M. SCRAPARI, A. KORANTZIS AND Z. PAPATHANASIOU From the Euromedica Medical Center, Department of Cytology, General Hospital of Athens and N Department of Obstetrics and Gynecology, El. Venizelou Maternity Hospital, Athens, Greece
ABSTRACT
The effectiveness ofintraurethral 5-fluorouracil and systemic administration ofinterferon-a2a in the therapy of condylomata acuminata or flat condylomata of the urethra is assessed. From March 1986 to September 1991, 1,372 male sexual partners of women with condylomata acuminata, flat condylomata or cervical intraepithelial neoplasia underwent urethroscopy and brush cytological examination of the urethra. Of these men 305 (22.23%) had intraepithelial human papillomavirus (confirmed cytologi.cally) and 284 were treated. The best treatment modalities, regardless of the type of lesion, were the combinations of 5-fluorouracil plus high (95.34%) and low (70.58%) dose interferon-a2a. Interferon-a2a can be used as first line treatment with 5-fluorouracil cream in patients with intraurethral condylomata acuminata or flat condylomata. KEY WORDS: urethra, condylomata acuminata, interferon alfa-2A, fluorouracil
Approximately two-thirds of male sexual partners and some with genital dysplasia or condylomata have human papillomavirus associated genital lesions. 1 - 6 It is evident that to restrict the incidence of genital human papillomavirus infection 7 both partners must be assessed early and treated properly. Treatment of urethral human papillomavirus infection has not been well documented and there have been few well controlled studies. 8 All methods in current use are, in some respects, unsatisfactory. 5-Fluorouracil has been used with variable results. Dretler and Klein successfully treated 19 of 20 men with intraurethral warts with 5% 5-fluorouracil cream instilled into the urethra after each voiding for 3 to 8 days. 9 Others have had less success, and have reported dysuria and retention of urine due to mucosa! edema after 5-fluorouracil therapy. 10 • 11 We assess the effectiveness of intraurethral application of 5-fluorouracil and systemic administration of interferon-a2a in the therapy of condylomata acuminata or flat condylomata of the urethra. MATERIALS AND METHODS
From March 1986 to September 1991, 1,372 male sexual partners of 1,523 women with condylomata acuminata, flat condylomata or cervical intraepithelial neoplasia underwent urethroscopy and brush cytological examination of the urethra. Of 1,372 examinations 305 (22.23%) showed intraepithelial human papillomavirus (confirmed cytologically). Mean patient age was 31.08 ± 4.1 years (range 18 to 55 years). Excluded from the study were patients with a granulocyte count of less than 2,000/ml. (normal 5,000 to 10,000/mL), platelet count less than 100,000/ml. (normal 150,000 to 300,000/ml.), renal dysfunction as measured by serum creatinine levels of more than 1.4 mg./dl. (normal 0.7 to 1.4), serum glutamic oxaloacetic transaminase more than 120 units (normal 8 to 40) and total bilirubin more than 2.0 mg./dl. (normal 0.4 to 1.2). Also excluded were patients with symptoms of heart disease, malignancy, psychiatric disorders necessitating medications or any neurological disorder, human immunodeficiency virus seropositivity, evidence of significant immunosuppression as determined by clinical evidence of opportunistic infection or treatment with immuno-
suppressive drugs, known or presumed hypersensitivity to interferon or 5-fluorouracil, previous gastrointestinal disorders, regular aspirin intake, a history of drug abuse and any type of anemia. Two treatment groups were established: group 1-intraurethral condylomata acuminata (30 patients) and group 2-intraurethral flat condylomata (254 patients). Group 1 patients were treated with a single dose of intraurethral 5-fluorouracil 5% cream each night applied with a cotton swab for 2 courses of 5 days (each course was followed by 5 days of no treatment), or a combination of 5-fluorouracil cream for 5 days followed by high dose interferon-a2a (single dose of3 X 10 6 IU subcutaneous interferon-a2a given abdominally) for 6 consecutive days (table 1). Group 2 patients were treated with a single dose of 5-fluorouracil 5% cream (as in group 1), or a combination of 5-fluorouracil cream for 5 days followed by either low dose (single dose of 1.5 X 10 6 IU subcutaneous interferon-a2a given abdominally) or high dose interferon-a2a for 6 consecutive days (table 2). Treatments were alternated as much as possible and attention was particularly focused on matching patients with condylomata acuminata according to the extent of the disease. Interferona2a and 5-fluorouracil were self-administered. AJI patients were evaluated at 40 days, and 3, 6, 9 and 12 months after treatment by brush cytological examination (mean followup 14.87 months, range 6 to 37). All patients used a condom during the study period. Recurrences within 1 year after treatment were considered indications of failure. Symptomatic side effects of interferon treatment included fever, chills, fatigue, malaise, nausea, vomiting and headaches, and were recorded daily by the patients.
Accepted for publication February 18, 1994. 2011
TABLE
1. Type of intraurethral lesions and treatment used Type of Intraurethral Lesions
Treatment
5-Fluorouracil 5-Fluorouracil plus interferon-a2a: Low dose High dose Totals
Condylomata Acuminata
Flat Condylomata
Totals
15
161
176
0 15 30
34 _§!)_ 254
--1±
34 284
2012
URETHRAL CONDYLOMATA ACUMINATA OR FLAT CONDYLOMATA TREATED WITH INTERFERON-a2a TABLE
Failures
2. Treatment failures 5-Fluorouracil Plus Interferon-a2a
5-Fluorouracil
Low Dose
Totals
High Dose
All pts.*
Yes
98
10
3
No
~
24 34
'71
Totals
176
74
111 173 284
Pts. with urethral condylomata acuminataf
Yes No
Totals Yes No
Totals
12
3
15
12 15 15 Pts. with urethral flat condylomatat
_Th
3
86
10 24 34
_Th
161
0 59 59
30 96 158 254
* Chi-square 59.83, p <0.001.
t Chi-square 10.8, p <0.01.
+Chi-square 53.55, p <0.001. RESULTS
Table 1 shows the type of lesions and treatment used. The overall cure rate was 60.91 %. Best treatment modalities, regardless of type of lesion, were the combinations of 5-fluorouracil plus either high dose (95.94%) or low dose (70.58%) interferon-cx2a (chi-square 59.83, p <0.001, table 2). Treatment failures among patients with intraurethral condylomata acuminata also are shown in table 2. The best treatment for condylomata acuminata was the combination of 5-fluorouracil plus high dose interferon-cx2a (80%, chi-square 10.8, p <0.01). The best treatment for intraurethral flat condylomata was 5-fluorouracil plus high dose interferoncx2a (100%, chi-square 53.55, p <0.001). Condylomata acuminata recurred at 3 (5 patients), 6 (1) and 9 (6) months in the 5-fluorouracil group, and at 3 months (3) in the 5-fluorouracil plus interferon-cx2a (high dose) group. All cases of recurrent flat condylomata in the 5-fluorouracil plus interferon-cx2a (low dose) group were diagnosed at 3 months. Biological side effects of treatment with interferon-cx2a included fever, chills, fatigue and malaise, and were observed in 71 of 108 patients (65. 75%) at the initiation of therapy. Fever usually occurred with the first 2 injections. The most predominant symptom was fatigue, which continued to some extent until interferon therapy was discontinued. The extent of the symptoms was dose-related. No episodes ofleukopenia (3,000 or fewer white blood cells per ml.) or thrombocytopenia (platelets 100,000/ml. or fewer) occurred in any patient who had received interferon. Complications with 5-fluorouracil occurred only in 12.5% of the patients, consisting of acute erosive chemical inflammation of the urethra. Complications occurred 7 to 19 days after commencement of treatment and subsided after 2 to 4 weeks. DISCUSSION
Deoxyribonucleic acid sequences of human papillomavirus types 5 and 2 were found in the semen of patients with chronic human papillomavirus infection. 12 Although human papillomavirus types 5 and 2 are not associated with lesions of the genital tract, the presence of the viral genome indicates that sexual transmission of human papillomavirus may occur by this route. Although formerly regarded as rare, urethral human papillomavirus infection is currently known to be common, particularly in men. Human papillomavirus type 16, 18 or 31 accounted for 70% of the positive urethral brushings 13 and, knowing that these types of human papillomavirus are associated with squamous cell carcinoma of the lower anogenital tract, 14 we can
state that urethral brushing is a necessary examination for all patients whose sexual partners have flat condylomata, condylomata acuminata or cervical intraepithelial neoplasia. Our detection rate of human papillomavirus infection by cytology was among the highest (22.23% versus 49% found by Cecchini et al 15 and 35% reported by Rosemberg 16 ), whereas previously reported values did not exceed 19%. 1 • 2 The presence of human papillomavirus infection in the urethra could have significant clinical ramifications, particularly in regard to the transmission of infection. Of all intraurethral condylomata 80% will occur within the distal 3 cm. 10 Several cases of venereal warts invading the bladder have also been reported. 10 • 17 Bissada et al recommended the use of 5% 5-fluorouracil for 20 minutes twice a week for 5 weeks. 18 From our study the recurrence rate of condylomata after 5-fluorouracil application was high (55.68%), which may be decreased by increasing the courses of 5-fluorouracil treatment. However, the high complication rate cannot be tolerated by the patients. Treatment of urethral human papillomavirus infection is not well documented and there have been few well controlled studies. Dretler and Klein successfully treated 19 of 20 men with intraurethral warts using 5% 5-fluorouracil cream instilled into the urethra after each voiding for 3 to 8 days. 9 Others have had less success, and Debenedictis et al 10 and Cetti 11 reported dysuria and retention of urine due to mucosal edema after 5-fluorouracil therapy. The success of local destructive methods for the treatment of urethral condylomata depends partly on the site and extent of the lesions. It may be difficult to destroy condylomata affecting the proximal urethra through a urethroscope, and exposure and direct treatment via urethrostomy may be necessary.11 The carbon dioxide laser is satisfactory for ablation of meatal lesions but not for proximal lesions unless the urethra is opened. 8 Some surgeons have used 5-fluorouracil cream as an adjunct to other modes of therapy. 8 Treatment of urethral condylomata is laborious and often followed by recurrences, and there is a genuine need for systemic therapy with interferon for this disease as for other types of genital human papillomavirus infection. In our study the combination of 5-fluorouracil and systemic administration of interferon-cx2a achieved cure rates of 96%, with an acceptable low complication rate. We believe that appropriate management for the disease in male sexual partners of women with human papillomavirus related lesions consists of the detection and treatment of all lesions, including intraurethral condylomata. Since the incidence of distal urethral warts is high, cytological examination of the urethra should be performed in all cases in an effort to diminish the reservoir of a virus strongly associated with cervical and penile urethral neoplasia. In conclusion, interferon-cx2a can be used as a first line treatment with 5-fluorouracil cream in patients with intraurethral condylomata acuminata or flat condylomata. REFERENCES
1. Levine, R. U., Crum, C. P., Herman, E., Silvers, D., Ferenczy, A. and Richart, R. M.: Cervical papillomavirus infection and intraepithelial neoplasia: a study of male partners. Obst. Gynec., 64: 16, 1986. 2. Sedlacek, T. V., Cunnane, M. and Carpiniello, V.: Colposcopy in the diagnosis of penile condyloma. Amer. J. Obst. Gynec., 154: 494, 1986. 3. Sand, P. K., Bowen, L. W., Blischke, S. 0. and Ostergard, D.R.: Evaluation of male consorts of women with genital human papillomavirus infection. Obst. Gynec., 68: 679, 1986. 4. Campion, M. J., Singer, A. and McCance, D. J.: Subclinical penile human papillomavirus infection in consorts of women with cervical neoplasia. Colposcopy Gynec. Laser Surg., 3: 11, 1987. 5. Krebs, H.B. and Schneider, V.: Human papillomavirus-associated lesions of the penis: colposcopy, cytology and histology.
URETHRAL CONDYLOMATA ACUIVIINATA OR FLAT CONDYLOMATA TREATED WITH INTERFERON-o:2a
Obst. Gynec., 70: 299, 1987. 6. Rosemberg, S. K. and Reid, R: Sexually transmitted papillomaviral infections in the male: L Anatomic distribution and clinical features. Urolog,J, 29: 488, 1987. 7. Nahhas, W. A, Marshall, M. L., Ponziani, J. and Jagielo, J. A: Evaluation of urinary cytology of male sexual partners of women with cervical intraepithelial neoplasia and human papillomavirus infection. Gynec. OncoL, 24: 279, 1986. 8. Oriel, J. D.: HPV infections of the urethra. In: Genital Papillomavirus Infections. Edited by Gross, Jablonska, Pfister and Stegner. New York: Springer-Verlag, p. 181, 1990. 9. Dretler, S. P. and Klein, L. A: The eradication of intraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. UroL, 113: 195, 1975. 10. Debenedictis T. J., Marmar, J. L. and Praiss, D. E.: Intraurethral condylomata acuminata: management and review of the literature. J. Urol., 118: 767, 1977. 11. Cetti, N. E.: Condyloma acuminatum of the urethra: problems in eradication. Brit. J. Surg., 71: 57, 1984. 12. Ostrow, R. S., Zachow, K R., Niimura, M., Okagaki, T., Muller,
13.
14. 15.
16. 17. 18.
2013
S., Bender, M. and Faras, A. J.: Detection of papillomavirus DNA in human semen. Science, 231: 731, 1986. Zderic, S. A., Carpiniello, V. L., Malloy, T. R. and Rando, R. F.: Urological applications of human papillomavirus typing using deoxyribonucleic acid probes for the diagnosis and treatment of genital condyloma. J. Urol., 141: 63, 1989. Rosemberg, S. K., Reid, R., Greenberg, M. and Lorincz, A.: Sexually transmitted papillomaviral infection in the male: II. The urethral reservoir. Urology, 32: 47, 1988. Cecchini, S., Cipparrone, I., Confortini, M., Scuderi, A., Meini, L. and Piazzesi, G.: Urethral cytology of Cytobrush specimens. A new technique for detecting subclinical human papillomavirus in men. Acta Cytol., 32: 314, 1988. Rosemberg, S. K.: Subclinical papilloma viral infection of male genitalia. Urology, 26: 554, 1985. Kleiman, H. and Lancaster, Y.: Condylomata acuminata of the bladder. J. Urol., 88: 52, 1962. Bissada, N. K., Redman, J. F. and Sulieman, J. S.: Condyloma of male urethra. Successful management with 5-fluorouracil. Urology, 3: 499, 1974.
THE JOURNAL OF UROLOGY Copyright © 1994 by AMERICAN UROLOGICAL ASSOCIATION, INC.
TREATMENT OF URETHRAL CONDYLOMATA ACUMINATA OR FLAT CONDYLOMATA WITH INTERFERON-a2a E. CARDAMAKIS, 1.-G. KOTOULAS, K. METALINOS, H. MANTOUVALOS, K. RELAKIS, M. SCRAPARI, A. KORANTZIS AND Z. PAPATHANASIOU From the Euromedica Medical Center, Department of Cytology, General Hospital of Athens and N Department of Obstetrics and Gynecology, El. Venizelou Maternity Hospital, Athens, Greece
ABSTRACT
The effectiveness ofintraurethral 5-fluorouracil and systemic administration ofinterferon-a2a in the therapy of condylomata acuminata or flat condylomata of the urethra is assessed. From March 1986 to September 1991, 1,372 male sexual partners of women with condylomata acuminata, flat condylomata or cervical intraepithelial neoplasia underwent urethroscopy and brush cytological examination of the urethra. Of these men 305 (22.23%) had intraepithelial human papillomavirus (confirmed cytologi.cally) and 284 were treated. The best treatment modalities, regardless of the type of lesion, were the combinations of 5-fluorouracil plus high (95.34%) and low (70.58%) dose interferon-a2a. Interferon-a2a can be used as first line treatment with 5-fluorouracil cream in patients with intraurethral condylomata acuminata or flat condylomata. KEY WORDS: urethra, condylomata acuminata, interferon alfa-2A, fluorouracil
Approximately two-thirds of male sexual partners and some with genital dysplasia or condylomata have human papillomavirus associated genital lesions. 1 - 6 It is evident that to restrict the incidence of genital human papillomavirus infection 7 both partners must be assessed early and treated properly. Treatment of urethral human papillomavirus infection has not been well documented and there have been few well controlled studies. 8 All methods in current use are, in some respects, unsatisfactory. 5-Fluorouracil has been used with variable results. Dretler and Klein successfully treated 19 of 20 men with intraurethral warts with 5% 5-fluorouracil cream instilled into the urethra after each voiding for 3 to 8 days. 9 Others have had less success, and have reported dysuria and retention of urine due to mucosa! edema after 5-fluorouracil therapy. 10 • 11 We assess the effectiveness of intraurethral application of 5-fluorouracil and systemic administration of interferon-a2a in the therapy of condylomata acuminata or flat condylomata of the urethra. MATERIALS AND METHODS
From March 1986 to September 1991, 1,372 male sexual partners of 1,523 women with condylomata acuminata, flat condylomata or cervical intraepithelial neoplasia underwent urethroscopy and brush cytological examination of the urethra. Of 1,372 examinations 305 (22.23%) showed intraepithelial human papillomavirus (confirmed cytologically). Mean patient age was 31.08 ± 4.1 years (range 18 to 55 years). Excluded from the study were patients with a granulocyte count of less than 2,000/ml. (normal 5,000 to 10,000/mL), platelet count less than 100,000/ml. (normal 150,000 to 300,000/ml.), renal dysfunction as measured by serum creatinine levels of more than 1.4 mg./dl. (normal 0.7 to 1.4), serum glutamic oxaloacetic transaminase more than 120 units (normal 8 to 40) and total bilirubin more than 2.0 mg./dl. (normal 0.4 to 1.2). Also excluded were patients with symptoms of heart disease, malignancy, psychiatric disorders necessitating medications or any neurological disorder, human immunodeficiency virus seropositivity, evidence of significant immunosuppression as determined by clinical evidence of opportunistic infection or treatment with immuno-
suppressive drugs, known or presumed hypersensitivity to interferon or 5-fluorouracil, previous gastrointestinal disorders, regular aspirin intake, a history of drug abuse and any type of anemia. Two treatment groups were established: group 1-intraurethral condylomata acuminata (30 patients) and group 2-intraurethral flat condylomata (254 patients). Group 1 patients were treated with a single dose of intraurethral 5-fluorouracil 5% cream each night applied with a cotton swab for 2 courses of 5 days (each course was followed by 5 days of no treatment), or a combination of 5-fluorouracil cream for 5 days followed by high dose interferon-a2a (single dose of3 X 10 6 IU subcutaneous interferon-a2a given abdominally) for 6 consecutive days (table 1). Group 2 patients were treated with a single dose of 5-fluorouracil 5% cream (as in group 1), or a combination of 5-fluorouracil cream for 5 days followed by either low dose (single dose of 1.5 X 10 6 IU subcutaneous interferon-a2a given abdominally) or high dose interferon-a2a for 6 consecutive days (table 2). Treatments were alternated as much as possible and attention was particularly focused on matching patients with condylomata acuminata according to the extent of the disease. Interferona2a and 5-fluorouracil were self-administered. AJI patients were evaluated at 40 days, and 3, 6, 9 and 12 months after treatment by brush cytological examination (mean followup 14.87 months, range 6 to 37). All patients used a condom during the study period. Recurrences within 1 year after treatment were considered indications of failure. Symptomatic side effects of interferon treatment included fever, chills, fatigue, malaise, nausea, vomiting and headaches, and were recorded daily by the patients.
Accepted for publication February 18, 1994. 2011
TABLE
1. Type of intraurethral lesions and treatment used Type of Intraurethral Lesions
Treatment
5-Fluorouracil 5-Fluorouracil plus interferon-a2a: Low dose High dose Totals
Condylomata Acuminata
Flat Condylomata
Totals
15
161
176
0 15 30
34 _§!)_ 254
--1±
34 284
2012
URETHRAL CONDYLOMATA ACUMINATA OR FLAT CONDYLOMATA TREATED WITH INTERFERON-a2a TABLE
Failures
2. Treatment failures 5-Fluorouracil Plus Interferon-a2a
5-Fluorouracil
Low Dose
Totals
High Dose
All pts.*
Yes
98
10
3
No
~
24 34
'71
Totals
176
74
111 173 284
Pts. with urethral condylomata acuminataf
Yes No
Totals Yes No
Totals
12
3
15
12 15 15 Pts. with urethral flat condylomatat
_Th
3
86
10 24 34
_Th
161
0 59 59
30 96 158 254
* Chi-square 59.83, p <0.001.
t Chi-square 10.8, p <0.01.
+Chi-square 53.55, p <0.001. RESULTS
Table 1 shows the type of lesions and treatment used. The overall cure rate was 60.91 %. Best treatment modalities, regardless of type of lesion, were the combinations of 5-fluorouracil plus either high dose (95.94%) or low dose (70.58%) interferon-cx2a (chi-square 59.83, p <0.001, table 2). Treatment failures among patients with intraurethral condylomata acuminata also are shown in table 2. The best treatment for condylomata acuminata was the combination of 5-fluorouracil plus high dose interferon-cx2a (80%, chi-square 10.8, p <0.01). The best treatment for intraurethral flat condylomata was 5-fluorouracil plus high dose interferoncx2a (100%, chi-square 53.55, p <0.001). Condylomata acuminata recurred at 3 (5 patients), 6 (1) and 9 (6) months in the 5-fluorouracil group, and at 3 months (3) in the 5-fluorouracil plus interferon-cx2a (high dose) group. All cases of recurrent flat condylomata in the 5-fluorouracil plus interferon-cx2a (low dose) group were diagnosed at 3 months. Biological side effects of treatment with interferon-cx2a included fever, chills, fatigue and malaise, and were observed in 71 of 108 patients (65. 75%) at the initiation of therapy. Fever usually occurred with the first 2 injections. The most predominant symptom was fatigue, which continued to some extent until interferon therapy was discontinued. The extent of the symptoms was dose-related. No episodes ofleukopenia (3,000 or fewer white blood cells per ml.) or thrombocytopenia (platelets 100,000/ml. or fewer) occurred in any patient who had received interferon. Complications with 5-fluorouracil occurred only in 12.5% of the patients, consisting of acute erosive chemical inflammation of the urethra. Complications occurred 7 to 19 days after commencement of treatment and subsided after 2 to 4 weeks. DISCUSSION
Deoxyribonucleic acid sequences of human papillomavirus types 5 and 2 were found in the semen of patients with chronic human papillomavirus infection. 12 Although human papillomavirus types 5 and 2 are not associated with lesions of the genital tract, the presence of the viral genome indicates that sexual transmission of human papillomavirus may occur by this route. Although formerly regarded as rare, urethral human papillomavirus infection is currently known to be common, particularly in men. Human papillomavirus type 16, 18 or 31 accounted for 70% of the positive urethral brushings 13 and, knowing that these types of human papillomavirus are associated with squamous cell carcinoma of the lower anogenital tract, 14 we can
state that urethral brushing is a necessary examination for all patients whose sexual partners have flat condylomata, condylomata acuminata or cervical intraepithelial neoplasia. Our detection rate of human papillomavirus infection by cytology was among the highest (22.23% versus 49% found by Cecchini et al 15 and 35% reported by Rosemberg 16 ), whereas previously reported values did not exceed 19%. 1 • 2 The presence of human papillomavirus infection in the urethra could have significant clinical ramifications, particularly in regard to the transmission of infection. Of all intraurethral condylomata 80% will occur within the distal 3 cm. 10 Several cases of venereal warts invading the bladder have also been reported. 10 • 17 Bissada et al recommended the use of 5% 5-fluorouracil for 20 minutes twice a week for 5 weeks. 18 From our study the recurrence rate of condylomata after 5-fluorouracil application was high (55.68%), which may be decreased by increasing the courses of 5-fluorouracil treatment. However, the high complication rate cannot be tolerated by the patients. Treatment of urethral human papillomavirus infection is not well documented and there have been few well controlled studies. Dretler and Klein successfully treated 19 of 20 men with intraurethral warts using 5% 5-fluorouracil cream instilled into the urethra after each voiding for 3 to 8 days. 9 Others have had less success, and Debenedictis et al 10 and Cetti 11 reported dysuria and retention of urine due to mucosal edema after 5-fluorouracil therapy. The success of local destructive methods for the treatment of urethral condylomata depends partly on the site and extent of the lesions. It may be difficult to destroy condylomata affecting the proximal urethra through a urethroscope, and exposure and direct treatment via urethrostomy may be necessary.11 The carbon dioxide laser is satisfactory for ablation of meatal lesions but not for proximal lesions unless the urethra is opened. 8 Some surgeons have used 5-fluorouracil cream as an adjunct to other modes of therapy. 8 Treatment of urethral condylomata is laborious and often followed by recurrences, and there is a genuine need for systemic therapy with interferon for this disease as for other types of genital human papillomavirus infection. In our study the combination of 5-fluorouracil and systemic administration of interferon-cx2a achieved cure rates of 96%, with an acceptable low complication rate. We believe that appropriate management for the disease in male sexual partners of women with human papillomavirus related lesions consists of the detection and treatment of all lesions, including intraurethral condylomata. Since the incidence of distal urethral warts is high, cytological examination of the urethra should be performed in all cases in an effort to diminish the reservoir of a virus strongly associated with cervical and penile urethral neoplasia. In conclusion, interferon-cx2a can be used as a first line treatment with 5-fluorouracil cream in patients with intraurethral condylomata acuminata or flat condylomata. REFERENCES
1. Levine, R. U., Crum, C. P., Herman, E., Silvers, D., Ferenczy, A. and Richart, R. M.: Cervical papillomavirus infection and intraepithelial neoplasia: a study of male partners. Obst. Gynec., 64: 16, 1986. 2. Sedlacek, T. V., Cunnane, M. and Carpiniello, V.: Colposcopy in the diagnosis of penile condyloma. Amer. J. Obst. Gynec., 154: 494, 1986. 3. Sand, P. K., Bowen, L. W., Blischke, S. 0. and Ostergard, D.R.: Evaluation of male consorts of women with genital human papillomavirus infection. Obst. Gynec., 68: 679, 1986. 4. Campion, M. J., Singer, A. and McCance, D. J.: Subclinical penile human papillomavirus infection in consorts of women with cervical neoplasia. Colposcopy Gynec. Laser Surg., 3: 11, 1987. 5. Krebs, H.B. and Schneider, V.: Human papillomavirus-associated lesions of the penis: colposcopy, cytology and histology.
URETHRAL CONDYLOMATA ACUIVIINATA OR FLAT CONDYLOMATA TREATED WITH INTERFERON-o:2a
Obst. Gynec., 70: 299, 1987. 6. Rosemberg, S. K. and Reid, R: Sexually transmitted papillomaviral infections in the male: L Anatomic distribution and clinical features. Urolog,J, 29: 488, 1987. 7. Nahhas, W. A, Marshall, M. L., Ponziani, J. and Jagielo, J. A: Evaluation of urinary cytology of male sexual partners of women with cervical intraepithelial neoplasia and human papillomavirus infection. Gynec. OncoL, 24: 279, 1986. 8. Oriel, J. D.: HPV infections of the urethra. In: Genital Papillomavirus Infections. Edited by Gross, Jablonska, Pfister and Stegner. New York: Springer-Verlag, p. 181, 1990. 9. Dretler, S. P. and Klein, L. A: The eradication of intraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. UroL, 113: 195, 1975. 10. Debenedictis T. J., Marmar, J. L. and Praiss, D. E.: Intraurethral condylomata acuminata: management and review of the literature. J. Urol., 118: 767, 1977. 11. Cetti, N. E.: Condyloma acuminatum of the urethra: problems in eradication. Brit. J. Surg., 71: 57, 1984. 12. Ostrow, R. S., Zachow, K R., Niimura, M., Okagaki, T., Muller,
13.
14. 15.
16. 17. 18.
2013
S., Bender, M. and Faras, A. J.: Detection of papillomavirus DNA in human semen. Science, 231: 731, 1986. Zderic, S. A., Carpiniello, V. L., Malloy, T. R. and Rando, R. F.: Urological applications of human papillomavirus typing using deoxyribonucleic acid probes for the diagnosis and treatment of genital condyloma. J. Urol., 141: 63, 1989. Rosemberg, S. K., Reid, R., Greenberg, M. and Lorincz, A.: Sexually transmitted papillomaviral infection in the male: II. The urethral reservoir. Urology, 32: 47, 1988. Cecchini, S., Cipparrone, I., Confortini, M., Scuderi, A., Meini, L. and Piazzesi, G.: Urethral cytology of Cytobrush specimens. A new technique for detecting subclinical human papillomavirus in men. Acta Cytol., 32: 314, 1988. Rosemberg, S. K.: Subclinical papilloma viral infection of male genitalia. Urology, 26: 554, 1985. Kleiman, H. and Lancaster, Y.: Condylomata acuminata of the bladder. J. Urol., 88: 52, 1962. Bissada, N. K., Redman, J. F. and Sulieman, J. S.: Condyloma of male urethra. Successful management with 5-fluorouracil. Urology, 3: 499, 1974.