Treatment of genital warts with an immune-response modifier (imiquimod)

Beutner, Karl R.; Spruance, Spotswood L.; Hougham, Andrina J.; Fox, Terrance L.; Owens, Mary; Douglas, John M.

doi:10.1016/s0190-9622(98)70243-9

Cited by 283 publications

(208 citation statements)

References 23 publications

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“…Three (19%) of the 16 patients who experienced complete clearance of warts had a recurrence develop during the 10-week follow-up period. 24 Subjects in the imiquimod arm experienced a significantly greater number of local inflammatory reactions, which ranged from pain and ulceration (8.3-10.4%) to itching (54.2%). Imiquimod 5% received FDA approval in 1997 and is marketed by MEDA AB, Graceway Pharmaceuticals, and iNova Pharmaceuticals under the trade name Aldara.…”

Section: Wwwajogorgmentioning

confidence: 98%

“…Imiquimod is capable of inducing a variety of cytokines, including INF-␣, TNF-␣, as well as IL-1, -6, and -8. Beurner et al 24 conducted a prospective, double-blind, placebo-controlled trial in 108 subjects, 51 of whom were randomly assigned to the imiquimod 5% arm and 57 to the placebo. Complete clearance of warts was reported for 37% of the imiquimod-treated patients, and in 0% of the placebo group (P Ͻ .001).…”

Section: Wwwajogorgmentioning

confidence: 99%

See 1 more Smart Citation

Green tea catechins for treatment of external genital warts

Meltzer

Monk

Tewari

2009

American Journal of Obstetrics and Gynecology

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This review evaluates the antiviral, antioxidant, and immunostimulatory properties of green tea catechins. Two randomized trials evaluating the activity and efficacy of green tea catechins in the management of external genital warts are presented, and the reported side effects associated with this topical treatment modality are outlined. Finally, the mechanism of action, percent of wart clearance, time to clearance, and toxicity profile of green tea catechins are compared with those of podofilox and imiquimod, 2 other patient-administered topical agents approved for treatment of anogenital warts.

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Section: Wwwajogorgmentioning

confidence: 98%

Section: Wwwajogorgmentioning

confidence: 99%

Green tea catechins for treatment of external genital warts

Meltzer

Monk

Tewari

2009

American Journal of Obstetrics and Gynecology

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“…Recently, alternative approaches have emerged utilizing topical biological response modifiers such as imiquimod, which bolsters cellular immune responses directed against virally infected keratinocytes and also exhibits antitumor effects. 37 In all, 19 of 51 patients (37%) who were treated topically with 5% imiquimod three times a week for 8 weeks achieved complete clearing compared with 0 of 57 (0%) of placebo-treated patients. 37 The goal of the present study was to design and test reagents targeted to the E6/E7 mRNA of HPV11, as an alternative means of suppressing papilloma progression.…”

Section: Discussionmentioning

confidence: 90%

“…37 In all, 19 of 51 patients (37%) who were treated topically with 5% imiquimod three times a week for 8 weeks achieved complete clearing compared with 0 of 57 (0%) of placebo-treated patients. 37 The goal of the present study was to design and test reagents targeted to the E6/E7 mRNA of HPV11, as an alternative means of suppressing papilloma progression. Library selection protocols were developed and used to identify accessible sites in an HPV target mRNA, whose expression has been shown to be critical in the development of HPV-associated lesions, namely the overlapping E6/E7 mRNAs.…”

Section: Discussionmentioning

confidence: 90%

Inhibition of papilloma progression by antisense oligonucleotides targeted to HPV11 E6/E7 RNA

et al. 2004

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Human papillomaviruses (HPVs) are recognized as important human pathogens, causing a spectrum of hyperproliferative lesions from benign warts to cervical dysplasias/ carcinomas. HPV-associated lesions require continued production of the oncogenic E6/E7 proteins, which are encoded by either bicistronic or overlapping mRNAs. Here we targeted the E6/E7 mRNA of HPV11, a type implicated in causation of genital warts, using molecular reagents. Accessible sites in the HPV11 E6/E7 RNA were identified using library selection protocols, and nucleic acids (DNAzymes, antisense oligonucleotides) targeted to these sites were constructed, and tested in cell culture and on human foreskin grafts. While DNAzymes were at least equally effective in cell culture, antisense oligonucleotides targeted to the region surrounding one of the library-selected sites (ASO 407 ) proved most effective in blocking progression of HPV11-induced papillomas in human foreskin grafts on immunodeficient mice. In total, 11 papillomas were treated with ASO 407 . Of these, four of seven small papillomas treated with ASO 407 showed loss of detectable virus by in situ hybridization (ISH), and in all four of these, papillomas were no longer evident grossly or histologically after treatment. When larger papillomas were treated, one of four showed loss of virus by ISH, associated with a minor decrease in papilloma size. Considering all 11 papillomas treated with ASO 407 , loss of viral staining by ISH was significantly different from that observed in controls (Po0.016), as was true for the seven small treated papillomas (Po0.012). DNAzymes targeted to the same site (or other library selected sites) did not produce statistically significant differences in ISH staining (Po0.15). Our results with ASO 407 appear to represent the first specific molecular therapy against a bona fide HPV infection, and provide a rational proof-of-principle strategy for development of molecular therapeutics targeting other HPV-associated lesions.

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“…Immunomodulators, such as imidazoquinolones that induce production of inflammatory cytokines have been used to potentiate the innate immune mechanism mediated through macrophages and dendritic cells (Bharti et al, 2009). Imiquimod TM , one of the imidazoquinolone compounds has shown efficacy and safety in clinical trials for the treatment of external HPV-infected genital warts (Beutner et al, 1998). In a phase II trial women treated with Imiquimod vaginal suppositories had significantly higher complete or partial regression of CIN 2/CIN 3 compared to the placebo group (Grimm et al, 2012).…”

Section: Discussionmentioning

confidence: 99%