Risk Stratification for Underlying Cervical Intraepithelial Neoplasia Grade (CIN)3+ in Reproductive-Age Women With Biopsy-Confirmed CIN2: Implications for Fertility-Preserving Management.

IntroductionManaging biopsy-confirmed cervical intraepithelial neoplasia grade 2 (CIN2) in women of reproductive age poses clinical challenges. Immediate treatment with large-loop excision of the transformation zone (LLETZ) is associated with a substantial risk of adverse obstetric outcomes. This study aimed to identify the risk factors for predicting CIN3+ lesions in reproductive-aged women with biopsy-diagnosed CIN2, to inform personalized management strategies that are particularly relevant to China's evolving fertility policies.MethodsThis retrospective cohort study analyzed the data from a regional cervical lesion screening database. Reproductive-aged women (<45 years) with biopsy-confirmed CIN2 who underwent subsequent LLETZ between 2016-2024 were included in the study (n=516). Pathological upgrade was defined as CIN3+ in the LLETZ specimen. Univariate and multivariate logistic regression analyses identified independent risk factors for pathological upgrade.ResultsFollowing LLETZ, 18.4% (95/516) of the women had CIN3+ lesions, indicating biopsy underestimation. HPV 16 (56.3%) and HPV 52 (27.5%) were the most prevalent genotypes in CIN3+ and CIN2- groups, respectively. Multivariable analysis identified three independent predictors: liquid-based cytology (TCT) ≥HSIL (OR = 6.308; 95% CI: 2.390-16.650; P<0.001); specific HR-HPV genotypes: HPV 16 infection (OR = 2.372; 95% CI: 1.165-4.831; P=0.017) and HPV 33 infection (OR = 3.263; 95% CI: 1.035-10.292; P=0.044); endocervical curettage (ECC) ≥CIN2 (OR = 3.067; 95% CI: 1.474-6.384; P=0.003). Age did not increase the risk of developing CIN3+ lesions.ConclusionThis risk-stratification model offers evidence-based guidance for optimizing individualized treatment decisions in clinical settings where fertility preservation is prioritized.