Recombinant human interferon- for condylomata acuminata: a randomized, double-blind, placebo-controlled study of intralesional therapy

Abstract

To assess the efficacy of a novel glycosylated mammalian cell derived recombinant human interferon-beta (r-hIFN-beta-1a) in the intralesional treatment of genital condylomata acuminata. The study was randomized, double-blind and placebo-controlled. Patients (n=60) with up to 8 distinct condylomata acuminata were randomized to receive either one million international units (IU) of r-hIFN-beta-1a or placebo intralesionally into each lesion, 3 times a week, for a total of 9 occasions. Biopsies were taken from each patient before enrolment to allow human papillomavirus (HPV) testing, and patients were tested for the development of anti-IFN-beta antibodies. Efficacy was assessed by measuring the complete response rate 3 months after treatment. The complete response rate was not significantly better with r-hIFN-beta-1a than with placebo. However, after 3 months, 73.3% of patients treated with r-hIFN-beta-1a had experienced at least a partial response to treatment, compared with 33.3% of placebo-treated patients. At 19 days and 6 weeks, r-hIFN-beta-1a produced a significantly larger reduction in the area of condylomata. Lesions with detectable HPV6 or 11 showed a trend towards a better response rate to treatment with r-hIFN-beta-1a than lesions where no HPV DNA was detected. The treatment was well tolerated. In the 5 patients who developed non-neutralizing anti-IFN-beta antibodies, therapeutic efficacy was not compromised. Intralesional r-hIFN-beta-1a was effective in the reduction of the size of genital condylomata acuminata.

Next‐generation treatment strategies for human papillomavirus‐related head and neck squamous cell carcinoma: where do we go?

“…IFN therapy proved to be beneficial in HPV infections such as condylomata acuminata , whereas the use of IFN therapy in HPV‐associated anogenital intraepithelial neoplasia has been assessed in several studies with contradicting results. Improved outcome for IFN‐treated patients was shown in some studies , whereas others reported no change in response rates between treated patients and controls . This might be attributed to the fact that local application seems to achieve better responses than systemic application .…”

Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation

“…The interaction of E6 and p300/CBP may thus block the growth-suppressing effects of interferon and allow HPV infections to persist for extended periods of time. Interferon therapy has also been suggested as a treatment for highgrade HPV infections, but variable results have been observed in clinical trails (6,14,15). Previously, we reported that keratinocytes that maintain HPV-31 episomes are highly sensitive to interferon treatment but that resistant populations quickly appear (9).…”

“…This activity of E6 is dependent upon its association with the transcriptional coactivators CBP/p300 but not upon the in-dase activity at 5 days following selection, cells were washed three times with PBS, fixed with 3% formaldehyde, and then washed again with PBS. Cells were then incubated at 37°C with fresh SA-␤-gal stain solution for 2 to 16 h. SA-␤-gal solution (pH 6.0) contained 1 mg/ml 5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside (X-Gal), 0.5 mM K 3 Fe(CN) 6 , 0.5 mM K 4 Fe(CN) 6 , 2 mM MgCl 2 , 150 mM NaCl, 40 mM citric acid, Na 2 HPO 4 for pH, and PBS up to 20 ml (2,33).…”

Topical Antineoplastic Agents in the Treatment of Mucocutaneous Diseases

“…Its efficacy in combination with CO 2 laser has been demonstrated by significantly decreased recurrence rates compared to those treated with CO 2 laser alone [84]. Patients treated with intralesional IFN-β 1a 3 times weekly for 3 weeks did not show a significantly better complete response rate than those treated with placebo, although partial response was significantly higher than in the control group [85]. Though head-to-head trials are lacking, topical and intralesional IFNs have not proven consistently to be superior to other treatments for condyloma acuminata.…”