Background: Cervical cancer remains a major public health concern, particularly in low-resource settings. Visual Inspection with Acetic Acid (VIA) is widely used for screening, but its high false positivity necessitates effective triaging methods. Biomarkers such as p16INK4a may improve diagnostic accuracy when applied to liquid-based cytology (LBC). Aim: diagnostic accuracy of p16INK4a immunostaining in LBC for detecting pre-invasive and invasive cervical lesions in VIA-positive women. Methods: This prospective study included premenopausal women aged 30–50 years attending the gynecology OPD who underwent opportunistic screening using VIA. Out of 700 women screened, 70 VIA-positive cases were enrolled. LBC samples were collected prior to colposcopy for cytology and immunostaining (p16INK4a Results: The mean age of participants was 42.7 ± 4.99 years, with most women belonging to lower socioeconomic groups. Common presenting complaints included vaginal discharge (45.7%) and lower abdominal pain (24.3%). VIA showed limited diagnostic accuracy with high false positivity rates. LBC demonstrated high sensitivity and specificity for detecting CIN1+ and CIN2+ lesions. Among VIA-positive women, 30% were positive for p16INK4a. Conclusion: p16INK4a and immunostaining on LBC samples is a promising and effective method for triaging VIA-positive women. It improves detection of high-grade cervical lesions, reduces unnecessary referrals, and can be implemented in low-resource settings to enhance cervical cancer screening programs.