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.