Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix

Abstract

Weekly topical treatment with imiquimod is effective in promoting regression of cervical high-grade squamous intraepithelial lesions.

A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival

“…By unravelling the immune profile of CIN3 regression versus persistence and by comparing this to a large cancer cohort, we have contributed to the etiological understanding of cervical carcinogenesis and have unraveled potential vulnerabilities that may be exploited in future conservative treatment strategies for CIN2-3. Some immune modulating treatments including local use of probiotics, interferon, and biological agents such as Imiquimod and 5-Fluorouracil, have already proven clinical benefit for CIN2-3 regression [ 73 , 74 , 75 ]. This focus on enabling CIN regression as a possible endpoint instead of quick surgical intervention is a welcoming approach to avoid overtreatment and underpins the growing importance of identifying robust markers for better patient stratification.…”

Importance of the Immune Microenvironment in the Spontaneous Regression of Cervical Squamous Intraepithelial Lesions (cSIL) and Implications for Immunotherapy

“…Imiquimod is an immune modulating cream which induces a local immune response at the cervix by binding to TLR7 on dendritic cells, monocytes and macrophages. TLR7 activation causes secretion of cytokines, including interferon (IFN)-α and IFN-γ, IL-6, IL-12, and tumor necrosis factor (TNF)-α, resulting in increased antigen presentation by LCs, higher natural killer cell activity and stimulate a type 1 T cell immune response to target HPV infected cells [ 23 , 138 , 139 , 140 , 141 ]. Most importantly, the cytokines stimulate a CD4+ and CD8+ pro-inflammatory T cell immune response by which HPV is cleared [ 23 , 138 , 139 , 141 ].…”

“…TLR7 activation causes secretion of cytokines, including interferon (IFN)-α and IFN-γ, IL-6, IL-12, and tumor necrosis factor (TNF)-α, resulting in increased antigen presentation by LCs, higher natural killer cell activity and stimulate a type 1 T cell immune response to target HPV infected cells [ 23 , 138 , 139 , 140 , 141 ]. Most importantly, the cytokines stimulate a CD4+ and CD8+ pro-inflammatory T cell immune response by which HPV is cleared [ 23 , 138 , 139 , 141 ]. Initially, topical imiquimod was used as a treatment for external anogenital warts, actinic keratoses, and superficial basal cell carcinomas.…”

“…Moreover, HPV infection was cleared in 60% of women in the imiquimod group [ 24 ]. A more recent RCT, conducted by Fonseca et al, showed a regression rate of 61% after 12 weeks of imiquimod application, compared to 22.5% in the control group [ 23 ]. In a recently performed patients’ preference multi-center, non-randomized trial in cHSIL patients in the Netherlands, 61 patients were treated with imiquimod.…”

“…Moreover, a positive correlation between preterm birth and higher excised volumes of cervical tissue has been described [ 19 , 22 ]. A relatively new, non-surgical treatment of cHSIL is imiquimod with clinical responses up to 60–73% [ 23 , 24 ]. Imiquimod is an immune modulating cream and a good alternative therapy for cHSIL, especially in women with (possible) future pregnancy wishes.…”