Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia–Grade 2

OBJECTIVE: To estimate the fraction of cervical intraepithelial neoplasia 2 (CIN 2) that might regress if untreated using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS). METHODS: We compared the cumulative occurrence of CIN 2 (n=397) and CIN 3 or more severe (n=542) diagnosed by the Pathology Quality Control Group in three trial arms-immediate colposcopy, human papillomavirus (HPV) triage, and conservative management-over the 2-year duration of the ALTS trial. A nonparametric test of trend was used to test for differences in the number of CIN 2 cases relative to number of CIN 3 or more severe cases across study arms with an increasing percentage of women referred to colposcopy at baseline. RESULTS: There were no significant differences in the cumulative 2-year cumulative CIN 3 or more severe diagnoses by study arm (10.9%, conservative management; 10.3%, HPV; 10.9%, immediate colposcopy) (Ptrend=.8), but there was a significant increase in CIN 2 diagnoses (5.8%, conservative management; 7.8%, HPV triage; 9.9%, immediate colposcopy) (Ptrend<.001) in the study arms, with increasing number of women referred to colposcopy at baseline. The relative differences in cumulative CIN 2 by study arm among women who tested HPV-16 positive at baseline were less pronounced (Ptrend=.1) than women who tested positive for other high-risk-HPV genotypes (Ptrend=.01). CONCLUSION: There was evidence that approximately 40% of undiagnosed CIN 2 will regress over 2 years, but CIN 2 caused by HPV-16 may be less likely to regress than CIN 2 caused by other high-risk-HPV genotypes. LEVEL OF EVIDENCE: II.