The efficacy of topical imiquimod in high‐grade cervical intraepithelial neoplasia: A systematic review and meta‐analysis

Abstract

ObjectiveA major side effect of cervical excision for high‐grade cervical intraepithelial neoplasia (CIN) is premature birth. A non‐invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high‐grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high‐risk human papillomavirus (hr‐HPV), compared with surgical treatment and placebo.MethodsDatabases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr‐HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses checklist.ResultsFive studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod‐treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03–8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59–33.27) for histological regression to ≤CIN 1. The hr‐HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62–23.77).ConclusionsThe histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Recent advances in treating female genital human papillomavirus related neoplasms with topical imiquimod

“…Comparing the efficacy of imiquimod to standard large loop excision a recent meta-analysis confirms the superiority of surgical excision in HSIL (OR: 14.81, 95% CI 6.59-33.27), 89 with a response rate of 37%-63% in imiquimod treated versus 92.3%-94% for large loop excision. Furthermore, the authors reported an HR-HPV clearance rate of 53.4% after imiquimod treatment and 66% after surgical excision (95% CI 0.62-23.77).…”

“…Imiquimod dose was 6.25 mg for vaginal suppository, 70 while those using imiquimod cream used either a half-sachet dose (6.25 mg) 74 up to a full sachet of Imiquimod 5% cream (12.5 mg). 72,89 Only one study 69 Several randomized controlled trials evaluated the role of imiquimod cream for CIN treatment: the first, compared a vaginal 6.25 mg imiquimod suppository for 14 weeks to a placebo in 69 CIN 2-3 untreated patients. 70 Histological complete remission was reported in 47% in the imiquimod arm and 14% in the placebo group (p-value = 0.008), while overall regression (defined as histologic regression to CIN1 or less at 20 weeks) in 73% versus 39%…”

“…Furthermore, the authors reported an HR-HPV clearance rate of 53.4% after imiquimod treatment and 66% after surgical excision (95% CI 0.62-23.77). 89 Recurrence in women treated with imiquimod was also evaluated in a randomized trial, comparing standard treatment (surgical or ablative excision) to twice weekly doses of imiquimod for 5 weeks before surgery. 69 No differences in dysplasia recurrence were reported, but the study was limited by slow accrual and prematurely stopped enrollment, thus limiting sample size and power.…”

“…The treatment schedule varied from 5 weeks 69 up to 16 weeks of administration. Imiquimod dose was 6.25 mg for vaginal suppository, 70 while those using imiquimod cream used either a half‐sachet dose (6.25 mg) 74 up to a full sachet of Imiquimod 5% cream (12.5 mg) 72,89 . Only one study 69 used 2.5 mg of Imiquimod 5% cream.…”

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success

“…For this reason, alternative conservative methods for SIL treatment are constantly being evaluated, and imiquimod (IMQ), a synthetic tolllike receptor 7 (TLR7) agonist, has generated attention for its potential to stimulate local antitumor and antiviral immune responses. Although studies have shown that IMQ is effective for treating vulvar intraepithelial neoplasia (VIN) [3], vulvar Paget disease [4], vaginal intraepithelial neoplasia (VaIN) [5], and CIN when compared to placebo or no intervention [6], its exact mechanism of action remains unclear [7].…”