Immunocytochemical staining for p16, Ki-67, and MCM2 in the detection of cervical lesions and cancer: a prospective observational study.

BACKGROUND

Cervical cancer remains a significant global health concern, necessitating effective screening strategies. Traditional methods, such as liquid-based cytology (LBC) and high-risk human papillomavirus (HR-HPV) testing, have limitations in sensitivity and specificity. This study aimed to evaluate the diagnostic performance of p16, Ki-67, and minichromosome maintenance protein 2 (MCM2) as biomarkers in cervical cancer screening, both as standalone methods and in combination, to improve early detection and risk stratification.

METHODS

This prospective study included 344 women who underwent LBC and HR-HPV testing, followed by the gold standard of colposcopy and biopsy. Immunocytochemical (ICC) staining for p16, Ki-67, and MCM2 was performed. The sensitivity, specificity, and Youden index were calculated to compare the efficacy of the single and combined screening methods.

RESULTS

LBC alone demonstrated suboptimal sensitivity, while HR-HPV testing exhibited low specificity. Among the single methods, dual staining of p16 paired with MCM2 (p16/MCM2) when using a high-risk threshold achieved the highest Youden index (0.55). The combination of LBC with p16/MCM2 yielded superior sensitivity (96.3%) and moderate specificity (42.6%), outperforming the combination of HR-HPV with dual staining of p16/MCM2. Importantly, all missed diagnoses were high-grade squamous intraepithelial lesion (HSIL) with cervical intraepithelial neoplasia (CIN) grades 2-3, and no cases of cervical cancer were missed.

CONCLUSIONS

HR-HPV-based primary screening with p16/Ki-67 triage may offer a viable strategy for cervical cancer detection. Combining LBC with p16/MCM2 dual staining demonstrated improved sensitivity and specificity compared to conventional methods. Notably, p16/MCM2 as a standalone assay achieved the highest Youden index when using a high-risk threshold. Further validation through multicenter studies is essential to confirm its generalizability.