Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Jun 1;137(6):1043-1053.
doi: 10.1097/AOG.0000000000004384.

Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix: A Randomized Controlled Trial

Bruno O Fonseca  1 , Júlio C Possati-Resende, Mila P Salcedo, Kathleen M Schmeler, Guilherme S Accorsi, José H T G Fregnani, Marcio Antoniazzi, Naitielle P Pantano, Iara V V Santana, Graziela M Matsushita, Ricardo Dos Reis
Affiliations
Clinical Trial

Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix: A Randomized Controlled Trial

Bruno O Fonseca et al. Obstet Gynecol. .

Abstract

Objective: To evaluate the histologic response rate of high-grade squamous intraepithelial lesions (HSIL) of the cervix after topical application of 5% imiquimod cream.

Methods: In this phase II trial, women with cervical HSIL (cervical intraepithelial neoplasia [CIN] 2-3) were randomly assigned to 250 mg of 5% imiquimod cream applied to the cervix weekly for 12 weeks, followed by loop electrosurgical excision procedure (LEEP) without preceding treatment. The sample size was calculated based on the HSIL regression rates previously reported by Grimm et al. The primary outcome was rate of histologic regression (to CIN 1 or less) in LEEP specimens. Prespecified secondary endpoints included surgical margin status and adverse events. Outcomes were stratified by human papillomavirus type and lesion grade (CIN 2 or CIN 3). Results were reported according to per protocol (PP) and intention-to-treat (ITT) analyses.

Results: Ninety women were enrolled: 49 in the experimental group and 41 in the control group. In the PP population, histologic regression was observed in 23 of 38 participants (61%) in the experimental group compared with 9 of 40 (23%) in the control group (P=.001). Surgical margins were negative for HSIL in 36 of 38 participants (95%) in the experimental group and 28 of 40 (70%) in the control group (P=.004). In the ITT population, rates of histologic regression also were significantly higher in the experimental group. Rates of adverse events in the experimental group were 74% (28/38) in the PP population and 78% (35/45) in the ITT population. Adverse events were mild, with abdominal pain being the most common. Three patients in the experimental group had grade 2 adverse events, including vaginal ulcer, vaginal pruritus with local edema, and moderate pelvic pain.

Conclusion: Weekly topical treatment with imiquimod is effective in promoting regression of cervical HSIL.

Clinical trial registration: ClinicalTrials.gov, NCT03233412.

PubMed Disclaimer

Conflict of interest statement

Financial Disclosure Júlio C. Possati-Resende disclosed they received money from Becton, Dickinson, and Company. The other authors did not report any potential conflicts of interest.

Figures

Fig. 1.
Fig. 1.. CONSORT (Consolidated Standards of Reporting Trials) flow chart of randomization and clinical trial progress. *Patients redrawn from intention-to-treat analysis. †Patients redrawn from per protocol analysis. ‡Excluded from per protocol and intention-to-treat analysis because they became pregnant during treatment and had not yet undergone loop electrosurgical excision procedure (LEEP). HSIL, high-grade squamous intraepithelial lesion.
Fonseca. Topical Imiquimod for HSIL of the Cervix. Obstet Gynecol 2021.
Fig. 2.
Fig. 2.. Disposable brush.
Fonseca. Topical Imiquimod for HSIL of the Cervix. Obstet Gynecol 2021.
Fig. 3.
Fig. 3.. Application of the imiquimod immunomodulator to the cervix. Beginning of the application (A); imiquimod reaching the entire transformation zone (B); imiquimod covering all lesion and transformation zone (C).
Fonseca. Topical Imiquimod for HSIL of the Cervix. Obstet Gynecol 2021.
Figure
Figure
No available caption
See this image and copyright information in PMC

References

    1. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. . Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–9. doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F - DOI - PubMed
    1. Martin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO, Keep SL. Surgery for cervical intraepithelial neoplasia. The Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD001318. doi: 10.1002/14651858.CD001318.pub2 - DOI - PMC - PubMed
    1. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006;367:489–98. doi: 10.1016/S0140-6736(06)68181-6 - DOI - PubMed
    1. Arbyn M, Kyrgiou M, Simoens C, Raifu AO, Koliopoulos G, Martin-Hirsch P, et al. . Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ 2008;337:a1284. doi: 10.1136/bmj.a1284.PMID:18801868 - DOI - PMC - PubMed
    1. Conner SN, Cahill AG, Tuuli MG, Stamilio DM, Odibo AO, Roehl KA, et al. . Interval from loop electrosurgical excision procedure to pregnancy and pregnancy outcomes. Obstet Gynecol 2013;122:1154–9. doi: 10.1097/01.AOG.0000435454.31850.79 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data