Diagnostic Value of CK7 Immunostaining Patterns in Cervical Intraepithelial Neoplasia Running title: CK7 value in CIN

Background: Accurate classification of cervical intraepithelial neoplasia (CIN) is essential for the appropriate treatment strategy and monitoring disease progression. While morphological evaluation remains the standard, interobserver variability and grading ambiguity—particularly in CIN2—necessitate additional biomarkers. This study evaluates CK7 immunostaining patterns and their association with CIN grade, Ki67 and p16 expression, and colposcopy findings. Methods: In a retrospective cross-sectional study, 106 histologically confirmed CIN cases (CIN1–CIN3) were assessed for CK7 expression patterns (negative, patchy, gradient, full-thickness). Ki67 and p16 scores (0–3) were obtained from prior pathology reports. Chi-square analysis was used to evaluate associations between biomarker expression and CIN grade. Results: CK7 expression was significantly associated with CIN grade (p < 0.001), with full-thickness staining observed in 68.8% of CIN3 cases and 0% of CIN1. High Ki67 and p16 scores (≥ 2) were also significantly associated with higher-grade CIN (p < 0.001). CK7 pattern correlated strongly with Ki67 (p > 0.001), p16 (p = 0.002), and abnormal colposcopic findings (p = 0.004). No significant association was found with past medical history of having CIN (p = 0.088). Conclusions: CK7 expression patterns reflect the severity of CIN and correlate with proliferation (Ki67) and HPV-driven transformation (p16). Full-thickness and gradient CK7 staining, when combined with Ki67 and p16, increase diagnostic accuracy and may inform clinical decision-making, particularly in morphologically ambiguous cases or settings with limited access to molecular testing.