First author, year | Interventions (IFN dosing group) | Patients randomised (N) | Localisation of warts | Age, (year, mean) | Female (n/N (%)) | No of warts (mean (SD)) | Previous treatment (n/N (%)) |
Alpha-IFN | |||||||
Petersen et al 3 | 5 MIU IFN-alpha 2b s.c. 3× per week (high dose) for 4 weeks after laser operation | 32 | Penile 18, vulvar 8, perianal/intra-anal 13, vagina/portio 3 | 27 | 10/32 (31%) | 0–5 warts: 6 6–10 warts: 10 11–50 warts: 14 >50 warts: 2 | Podophyllin 32, surgery 17, cryotherapy 5 |
Placebo s.c. 3× per week for 4 weeks after laser operation | 23 | Penile 13, vulvar 10, perianal/intra-anal 11, vagina/portio 3 | 23 | 9/23 (39%) | 0–5 warts: 3 6–10 warts: 8 11–50 warts: 9 >50 warts: 3 | Podophyllin 23, surgery 17, cryotherapy 3 | |
Eron et al 9 | 3 MIU IFN-alpha 2a s.c. 3× per week for 8 weeks (high dose), treatment began within 2 weeks after removal of warts via cryotherapy in weekly intervals | 49 | Penile 19, vulvar 9, scrotal 1, perianal 2, perineal 4, multiple warts 14 | Median 23 | 21/49 (43%) | Median 6.8 | 32/49 (65%) |
Placebo s.c. 3× per week for 8 weeks, treatment began within 2 weeks after removal of warts via cryotherapy in weekly intervals | 48 | Penile 26, vulvar 4, scrotal 0, perianal 0, perineal 3, multiple warts 15 | Median 25 | 13/48 (27%) | Median 7.8 | 39/48 (81%) | |
Handley et al 10 | 3 MIU IFN-alpha 2a s.c. 3× per week in the first week (high dose), then IFN 2× per week and cryotherapy 1× per week for 6 weeks | 29 | Male: inner and outer prepuce, glans, penile shaft, perianal, anal canal, terminal urethra Female: introitus, vulva, vaginal, perianal, anal canal | n.s. | 14/29 (48%) | Median 10 | n.s. |
Placebo s.c. on 3× per week in the first week, then placebo 2× per week and cryotherapy 1× per week for 6 weeks | 31 | 22/31 (71%) | Median 13 | ||||
The Condylomata International Collaborative Study Group 19938 | 3 MIU IFN-alpha 2a s.c. 3× per week (high dose) for 4 weeks after CO2 laser vaporisation | 74 | Genital 37, perianal 5, both 32 | Median 25 | 52/74 (70%) | ≤10 warts: 30 >10 warts: 24 not countable 20 | n.s. |
Placebo (vehicle) s.c. 3× per week for 4 weeks after CO2 laser vaporisation | 72 | Genital 36, perianal 0, both 36 | Median 23 | 49/72 (68%) | ≤10 warts: 30 >10 warts: 23 not countable 19 | ||
Armstrong et al 7 | 3 MIU IFN-alpha 2a s.c. 3× per week (high dose) for 1 week, then 2× per week IFN plus podophyllin for 6 weeks | 61 | External genitalia and/or perianal area, some patients with internal warts | n.s. | 26/61 (43%) | 14.2 (12.6) | None (inclusion criterion) |
Placebo s.c. 3× per week for 1 week, then 2× per week placebo plus podophyllin for 6 weeks | 63 | 41/63 (65%) | 19.7 (18.6) | ||||
Armstrong et al 6 | 3 MIU IFN-alpha-2a s.c. 3× per week (high dose) for 10 weeks in combination with ablative therapy | 83 | Genital 50, perianal 7, both 25 | n.s. | n.s. | 1–5 warts: 21 6–10 warts: 22 11–15 warts: 7 16–20 warts: 7 >20 warts: 6 not countable 19 | n.s. |
1 MIU IFN-alpha-2a s.c. 3× per week (low dose) for 10 weeks in combination with ablative therapy | 85 | Genital 54, perianal 7, both 23 | 1–5 warts: 17 6–10 warts: 16 11–15 warts: 15 16–20 warts: 4 >20 warts: 11 not countable 21 | ||||
Placebo s.c. 3× per week for 10 weeks in combination with ablative therapy | 81 | Genital 52, perianal 7, both 22 | 1–5 warts: 14 6–10 warts: 20 11–15 warts: 9 16–20 warts: 6 >20 warts: 6 not countable 26 | ||||
Hohenleutner et al 4 | 1 MIU IFN-alpha 2b s.c. for 6 consecutive days (low dose), with another 6-day treatment cycle after 2 weeks. Treatment started immediately after CO2 laser ablation. | 19 | Perigenital, perianal, intra-anal, intravaginal | 29 (range 18–52) | 5/19 (26%) | n.s. | n.s. |
No treatment after CO2 laser ablation | 16 | 28 (range 22–38) | 5/16 (31%) | ||||
Roemisch et al 25 | 3 MIU IFN-alpha 2a s.c. in three cycles of 5 consecutive days with 2 weeks without treatment in between (high dose), starting after laser treatment | 24 (1:1 randomisation ratio assumed) | Vulva 21, vagina 6, portio 8, perianal 11, rectum 2 | 26.7 | All female | n.s. | 7/24 (29.2%) |
1 MIU IFN-alpha 2a s.c. in three cycles of 5 consecutive days with 2 weeks without treatment in between (low dose), starting after laser treatment | |||||||
Beta-IFN | |||||||
Kokelj et al 2 | 3 MIU IFN-beta 1× per day for 10 days (very high dose) after diathermocoagulation (after 1 month of follow-up all patients were treated with monthly diathermocoagulation if necessary) | 26 | Glans, coronal sulcus, inner surface of the prepuce and shaft of the penis | 34 (range 20–53) | All male | n.s. | n.s. |
3 MIU IFN-beta 1× per day for 10 days, after 1 month treated with electrocautery | 25 | 31 (range 19–54) | |||||
No treatment plus diathermocoagulation (after 1 month of follow-up all patients were treated with monthly diathermocoagulation if necessary) | 33 | 34 (range 23–61) | |||||
Bonnez et al 24 | 2 MIU/m² IFN-beta 3× per week (high dose), cryotherapy in 10-day intervals, both for 6 weeks | 25 | Men: penile 88.7%, foreskin 5.2%, glans 2%, pubis and groin 1.6%, scrotum 0.8%, urethral meatus 0.4% Women: labia minora and clitoris 36.1%, labia majora 23.9%, introitus 18.7%, perianal 14.2%, pubis and groin 7.1% | 26.7 | 6/25 (24%) | Median 5 | 24.5% |
4 MIU/m² IFN-beta three times a week (very high dose), cryotherapy in 10-day intervals, both for 6 weeks | 25 | 25.3 | 9/25 (36%) | Median 8.5 | 18.4% | ||
Gamma-IFN | |||||||
Zouboulis et al 11 | 0.75 MIU IFN-gamma s.c. 1× per day for 7 days (low dose), beginning after ablative therapy (electrocautery or CO2 laser) | 10 | Penis or vulva 1, perianal/intra-anal 3, genital and anal 6 | Median 27 | 2/10 (20%) | n.s. | All (inclusion criterion) |
No treatment after ablative therapy (electrocautery or CO2 laser) | 10 | Penis or vulva 1, perianal/intra-anal 2, genital and anal 5 | Median 28 | 2/10 (20%) | |||
Direct comparison of alpha-, beta- and gamma-IFN | |||||||
Bonnez et al 5 | 2 MIU/m² IFN-alpha n1 s.c. 3× per week (high dose), cryotherapy in 10-day intervals, both for 6 weeks | 36 | Men: penile shaft 75.1%, foreskin 11.3%, pubis and groin 7.2%, glans 2.1%, anus 2.0%, urethral meatus 0.4% Women: anus 31.3%, labia majora 28.8%, labia minora/clitoris 21.2%, introitus 12.6%, pubis and groin 6.1% | 26.3 | 5/36 (14%) | Median 11 | 33.3% |
2 MIU/m² IFN-beta s.c. 3× per week (high dose), cryotherapy in 10-day intervals, both for 6 weeks | 40 | 28.1 | 7/40 (18%) | Median 8 | 37.5% | ||
2 MIU/m² IFN-gamma s.c. 3× per week (high dose), cryotherapy in 10-day intervals, both for 6 weeks | 37 | 28.5 | 5/37 (14%) | Median 9 | 27.0% | ||
Placebo s.c. 3× per week, cryotherapy in 10-day intervals, both for 6 weeks | 38 | 30.1 | 7/38 (18%) | Median 10 | 23.7% |
IFN, interferon; MIU, million International Units, s.c., subcutaneously, n.s., not stated.