Six studies were included in the review (n=974); four were phase II open-label studies and two were double-blind placebo-controlled trials. Both RTCs scored three on the Jadad scale. The quality scores of the open-label studies ranged from one to three.
Complete clearance rates ranged from 11% to 72% (circumcised men 11% to 42%; uncircumcised men 57% to 62%; women 52% to 72%).
The effect size for circumcised men was 0.33 (95% CI: 0.24, 0.42) (2 studies, n=89) for three times a week treatment and 0.37 (95% CI: 0.26, 0.48) (2 studies, n=81) for once-daily treatment. The effect size for uncircumcised men was 0.62 (95% CI: 0.38, 0.86) (1 study, n=34) for three times a week treatment and 0.57 (95% CI: 0.39, 0.75) (1 study, n=30) for once-daily treatment regimen. The effect size for women was 0.59 (95% CI: 0.50, 0.68) (3 studies, n=103) for three times a week treatment and 0.67 (95% CI: 0.56, 0.78) (2 studies, n=74) for once-daily treatment. No evidence of significant statistical heterogeneity was found.
No difference in aggregate proportions of successfully treated patients was found in the different application regimens (three times a week or once daily) for circumcised men (z=0.11, p=0.9) and for women (z=0.38, p=0.7). No difference between treatment regimens was found in a single study of uncircumcised men (z=0.15, p=0.9). The effect size was higher in women than in circumcised men regardless of frequency of application (z=3.9, p=0.0001 three times a week; z= 4.2, p=0.0001 once daily). Imiquimod treatment was more effective in uncircumcised men than circumcised men, but only for three times a week application (z=3.3, p=0.001) compared with the once-daily regimen (z=1.93, p=0.054). Results from random effects model did not substantially affect the magnitude or direction of effect.
Withdrawal from treatment due to cutaneous reactions was similar for the two treatment regimens. The proportion of women and uncircumcised men who required a rest period from treatment was higher in the once-daily treatment regimen (z=2.4, p=0.02) than the three times a week regimen (z=2.7, p=0.007); no statistically significant difference was found in circumcised men.