p16INK4a/Ki67 Dual-Staining Immunocytochemistry to Refer Women Infected by High-Risk Human Papillomavirus for...

Cervical cancer is still a significant global health issue, especially in low- and middle-income countries. Human papillomavirus (HPV) infection is known to be the primary etiological factor in the development of cervical cancer. The identification of high-risk HPV (HR-HPV) infections in cervical cancer screening is becoming crucial for early detection and management of cervical pre-neoplasia. However, HPV testing requires triage markers since HR-HPV infections are widespread in the target population, of which only a small fraction requires detailed clinical workup by colposcopy.

p16INK4a is a tumor suppressor protein that has emerged as a promising surrogate marker for HPV infection. In combination with a proliferation marker Ki67 in one diagnostic test kit referred to as CINtecPlus® or dual stain (DS), it revealed excellent sensitivity and specificity profiles to detect clinically relevant CIN2+ lesions among HPV-infected women in large screening cohorts.

This review examines the role of the cytology CINtecPlus® test (DS test) as a triage marker to identify patients with CIN2+ lesions among HPV+ tested women and summarizes the most recent recommendations for its clinical use.