Clinical evaluation of p16/Ki-67 dual staining in cervical cytology

The Papanicolaou staining method and primary cervical screening for HPV are widely used to detect precancerous conditions and cervical cancer. Patients diagnosed with ASCUS/LSIL are at risk for progression of dysplasia (CIN2+) and require follow-up monitoring. The prognosis for HPV-positive women remains uncertain, necessitating refinement of tests to predict outcomes of persistent HPV infection. Therefore, an effective biomarker is needed to separate patients based on the results of pre-cervical screening. Two oncoproteins can be used for this purpose: p16 acts as a cell cycle regulatory protein that induces cell cycle arrest, and Ki-67, which is a marker of cell proliferation. They are not expressed in cervical epitheliocytes under physiological conditions. The simultaneous identification of these two proteins during additional staining of cytological preparations suggests the presence of cell cycle dysregulation mediated by persistent HPV infection and is also a predictor of the development of severe cervical lesions. The sensitivity of this test for the diagnosis of moderate and severe cervical dysplasia was found to be high; p16/Ki-67 dual immunostaining has comparable sensitivity and increased specificity for CIN2+ screening compared with the detection of high-risk HPV types. This review reflects the value of p16/Ki-67 dual staining in cervical cytology in distinguishing patients with existing cervical dysplasia. Key words: p16/Ki-67 co-expression, cytology, HPV, cervical screening, CIN