Abstract:

Cervical cancer is a malignant tumor that seriously threatens women's health, and its occurrence is closely related to persistent infection of high-risk human papilloma virus (HR-HPV). Although the current screening strategies mainly based on cytology and HPV testing have reduced the burden of cervical cancer, the low specificity of HR-HPV testing has led to a large number of transient infected individuals being referred for unnecessary colposcopy, which has become a challenge in clinical practice. The p16/Ki-67 dual staining technique synchronously detects the co-expression of p16^INK4a and Ki-67 proteins through immunocytochemical methods, which can objectively identify the state of cell transformation driven by HR-HPV and provides an excellent solution for the triage management of HR-HPV positive individuals. A large amount of evidence shows that for the detection of high-grade cervical intraepithelial neoplasia (CIN2+), the dual staining technique not only has a sensitivity of over 90%, but its specificity (approximately 70%-85%) is significantly better than that of cytological triage. It can reduce colposcopy referrals by about 30%-50%. Moreover, its negative predictive value (>97%) supports extending the follow-up interval for negative individuals, thus optimizing the screening efficiency. The p16/Ki-67 dual staining technique, through accurate risk stratification, significantly reduces overdiagnosis and over-treatment while ensuring the detection rate of lesions. It has become one of the triage tools with the most evidence-based support in the optimization of cervical cancer screening strategies.

Key words: Ki-67 antigen, Genes, p16, Uterine cervical diseases, Cytodiagnosis, Immunohistochemistry, Mass screening, p16/Ki-67 dual staining