Improving Detection of CIN2+ and CIN3+ Lesions: Evaluation of E6/E7 mRNA, P16, and Ki‐67, Individually and in Combination

ABSTRACT

Cytology screening has lower cervical precancer sensitivity than HPV DNA testing, which lacks specificity. To overcome this limitation, we assessed the diagnostic performance of E6/E7 mRNA, P16, and Ki‐67, both alone and in combination, in detecting cervical intraepithelial neoplasia grade 2 or higher (CIN2+). A total of 403 cervical samples were collected from the First People's Hospital of Nanning between January 2019 and January 2024, and each biomarker was evaluated for its diagnostic accuracy. E6/E7 mRNA showed moderate performance, with 68.2% sensitivity and 61.8% specificity in detecting CIN2+ lesions. P16 exhibited superior performance, achieving 82.2% sensitivity and 90.1% specificity. Although Ki‐67 showed the highest sensitivity at 95%, it had the lowest specificity at 27.2%. The combination of P16 and Ki‐67 yielded the best diagnostic results, with 90% sensitivity and 79.8% specificity for CIN2+, representing a significant enhancement over individual biomarkers. These findings highlight the superior accuracy of P16, especially when combined with Ki‐67, in detecting both CIN2+ and CIN3+ lesions. This approach improves high‐risk lesion detection by reducing false negatives. Incorporating P16/Ki‐67 biomarkers enhances screening sensitivity/specificity and clinical outcomes.