Retinoids for preventing the progression of cervical intra-epithelial neoplasia

  • Review
  • Intervention

Authors


Abstract

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 cases of 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 the regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation that may have potential for the treatment of CIN.

Objectives

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

Search methods

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

For the 2013 update, the searches were re-run as follows: CENTRAL, Issue 3, 2013; MEDLINE, April, Week 2, 2013; and Embase, Week 16, 2013. In Novemeber 2015 the searches were updated: CENTRAL, Issue 10, 2015; MEDLINE, Nov, Week 1, 2015; and Embase, Week 46, 2015.

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 effects on CIN2 and CIN3 of the retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally. Two examined the effect of all-trans-retinoic acid administered topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally to human immunodeficiency virus (HIV)-positive participants with CIN1 and condyloma.

Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, and 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 that seen with 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 nonsignificant dose-related trend toward increased rates of complete and partial regression compared with placebo. One study reported significantly worse outcomes 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 the 2010, 2013 and 2015 updates, no new studies were identified for inclusion, therefore the review has been marked as stable.

Authors' conclusions

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

Plain language summary

The use of retinoids (vitamin A derivatives) to prevent progression of cervical intra-epithelial neoplasia (CIN)

Cervical cancer is preceded by cervical intra-epithelial neoplasia (CIN). Surgery for CIN is effective in 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 in causing regression of severe CIN3 but may have activity in moderate CIN2. Data are inadequate to allow assessment of whether the retinoids studied are effective in preventing progression of any grade of CIN.