Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia-Grade 2

There is increasing evidence that a significant proportion of CIN 2 lesions found in cervical cancer screening programs are not precancerous and may resolve without treatment. The present study evaluated the percentage of CIN 2 regression if untreated using three different management strategies for referring women to colposcopy using data from the Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS). Over the 2-year duration of the ALTS, the investigators compared the cumulative occurrence of CIN 2 (n = 397) and CIN 3 or more severe (n = 542) in three treatment arms: 1) conservative management (CM arm) (referral to colposcopy only if the lesion at baseline was identified by cytology as high-grade squamous intraepithelial lesion [HSIL]); 2) human papillomavirus (HPV) triage (HPV arm) (referral to colposcopy if the HPV test result at baseline was positive, missing, or identified by cytology as HSIL); or 3) immediate colposcopy (IC arm) (referral of all patients to colposcopy at baseline). A nonparametric test for trend across study arms was used to test for differences in the number of CIN 2 cases relative to number of CIN 3 or more severe cases referred to colposcopy. At baseline, 10.2% of the women in the CM arm, 55.5% of women in the HPV arm, and 71.7% of women in the IC arm were sent to colposcopy. Over the 2-year duration of ALTS, the proportion of women diagnosed with CIN 3 or more severe did not differ significantly among the three study arms: CM, 10.9%; HPV, 10.3%; and IC, 10-9% (P(trend) = 0.8). However, the percentage of women diagnosed with CIN 2 was significantly greater for the referral strategies that sent larger proportions of women to colposcopy: CM, 5.8%; HPV, 7.8%; and IC, 9.9% (P(trend) < 0.001). Among high-risk-HPV genotypes identified at baseline (except HPV 16), the trend of increased CIN 2 diagnoses by study arm with increasing proportion of women sent to colposcopy also was observed (P(trend) = 0.01); among women with HPV 16, the trend was nonsignificant (P(trend) = 0.1). These data suggest that over 40% of CIN 2 diagnosed over 2 years may represent regressive lesions destined to resolve without treatment. A similar pattern occurs in high-risk-HPV genotypes except HPV 16-positive CIN 2, which appears less likely to regress.