Markers of cervical intraepithelial neoplasia grade 2 regression and subsequent risk of CIN3

Cervical intraepithelial neoplasia (CIN) grade 2 (CIN2), a precursor to cervical cancer, can regress without treatment, but the prognostic value of different regression markers remains unclear. Using electronic medical records from 5,938 women with newly detected CIN2 managed with delayed treatment at Kaiser Permanente Northern California, we estimated the frequency of histologic, cytologic, and virologic regression within 1 year of CIN2 diagnosis and the subsequent 3-year risk of CIN grade 3 or worse (CIN3+). Histologic regression was common but remained associated with appreciable subsequent CIN3+ risk. In contrast, HPV-negative results were associated with lower subsequent CIN3+ risk than normal histology or normal cytology (2.8% vs. 7.0% and 4.2%, respectively; both p < 0.001). Combined HPV-negative and normal cytology results identified the lowest risk group (1.3%; all pairwise comparisons, p < 0.001). These findings suggest that HPV clearance may be a more informative endpoint for therapeutic trials and marker for guiding surveillance of CIN2.