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Can Retinoids Prevent CIN Progression?

Can Retinoids Prevent CIN Progression?

Retinoids may have some effect on regression of certain grades of cervical intraepithelial neoplasia (CIN) but do not prevent disease progression, according to the results of an intervention review conducted by the Cochrane Gynaecological Cancer Group.1
Retinoids, derivatives of vitamin A, are potent modulators of epithelial cell growth and differentiation that play a role in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes. Their ability to modulate epithelial cell growth and differentiation makes them a promising candidate for the treatment of CIN.
To evaluate whether the use of retinoids can cause regression or prevent progression of CIN, researchers reviewed 5 randomized controlled trials that studied retinoids for the treatment of CIN. Two trials evaluated the effects of the oral retinoids fenretinide and aliretinoin on CIN 2 and CIN 3, and 2 other trials studied the effects of topical administration of all-trans-retinoic acid to the cervix. The final study focused on the use of oral isotretinoin in HIV-positive women with CIN 1 and condyloma, a type of human papillomavirus infection.
The use of retinoids included in this review did not prevent the progression to higher grades of CIN, nor did they have any significant effect on the regression of CIN 3. However, the use of retinoids may have some effect on the regression of CIN 2. In one of the included studies, retinoid use was associated with a greater complete regression of CIN 2 compared with placebo (borderline statistical significance). In another study, there was an insignificant dose-related trend toward increased rates of complete and partial regression of CIN 2, wrote the review authors. Significantly worse outcomes in women who were given retinoids were reported in one of the included studies. In all of the studies, the retinoid provided was reported to be well tolerated.
Although surgical treatment for CIN can effectively reduce the risk of invasive carcinoma, medical treatments are lacking. The review authors explained that the benefit of an effective chemopreventive drug would be the avoidance of surgery, which could reduce costs and minimize morbidity related to workups and treatment. The retinoids evaluated in this review do not effectively prevent the progression of CIN of any grade or cause regression of CIN 3. However, retinoids may have some effect on causing regression of CIN 2.

Pertinent Points:
- Retinoids are not associated with regression of CIN 3 but may have some effect on regression in CIN 2.
- Retinoids do not effectively prevent progression of any grade of CIN.


1. Helm CW, Lorenz DJ, Meyer NJ, et al. Retinoids for preventing the progression of cervical intra-epithelial neoplasia. Cochrane Database Syst Rev. 2013;6:CD003296. DOI: 10.1002/14651858.CD003296.pub3.
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