The use of retinoids (vitamin A derivatives) to prevent cervical intraepithelial neoplasia (CIN) progression

Helm CW, Lorenz DJ, Meyer NJ, Rising WW R, Wulff JL

Published Online:

January 19, 2011

Cervix cancer is preceded by cervical intraepithelial neoplasia (CIN). Surgery for CIN is effective at reducing the risk of subsequent invasive carcinoma. An effective chemo-preventive agent might avoid the need for surgery and reduce the cost and morbidity of work-up and treatment. Retinoids are natural and synthetic derivatives of naturally occurring Vitamin A. Overall, the retinoids studied are not effective at causing regression of severe intra-epithelial neoplasia (CIN3) but may have activity in moderate intra-epithelial neoplasia (CIN2). There is inadequate data to assess whether the retinoids studied are effective at preventing progression of any grade of CIN.

Abstract (click to read)

Background:

Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation and may have potential for the treatment of CIN.

Objectives:

To ascertain whether retinoids can cause regression or prevent progression of CIN.

Search strategy:

We searched the Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3,2010), MEDLINE and EMBASE (July 2010).

Selection criteria:

Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women.

Data collection and analysis:

Two review authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials.

Main results:

Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effect on CIN2 and CIN3 of retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally and two examined the effect of all-trans-retinoic acid given topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally in HIV positive patients with CIN1 and condyloma.

Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, whilst the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over placebo, which was of borderline statistical significance, odds ratio (OR) 0.5 (95% confidence interval (CI) 0.25 to 1.02). The other study reported a non-significant dose-related trend towards increased rates of complete and partial regression compared with placebo. One study reported a significantly worse outcome in women receiving retinoid, OR for regression 6.00 (95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated.

In this update no new studies were identified for inclusion.

Authors' conclusions:

The retinoids studied are not effective at causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 is inadequate. Retinoids are not effective at preventing progression of CIN of any grade. At the doses given and duration of treatment studied, the retinoids were reasonably well-tolerated.

This record should be cited as:

Helm CW, Lorenz DJ, Meyer NJ, Rising WW R, Wulff JL. Retinoids for preventing the progression of cervical intra-epithelial neoplasia. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD003296. DOI: 10.1002/14651858.CD003296.pub2

Assessed as up to date:

October 12, 2010

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Gynaecological > Cervix

Gynaecology > Cancer > Cervix

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

The use of retinoids (vitamin A derivatives) to prevent cervical intraepithelial neoplasia (CIN) progression

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