Immediate histological risk and one-year outcomes following P16-based triage of HPV-positive women

Primary high-risk human papillomavirus (hrHPV) testing improves the sensitivity of cervical cancer screening but requires effective triage to distinguish women with clinically relevant precancer from those with transient infection. p16 immunocytochemistry reflects HPV-driven epithelial transformation and may help identify women at higher risk of clinically cervical precancer. We evaluated the association of baseline p16 status with triage performance, immediate histological risk stratification and one-year follow-up outcomes in a cervical screening cohort. We retrospectively analysed 11,263 women who underwent cervical screening at The Second Hospital of Jilin University from February 2024 to January 2026. Histological outcomes were available for 2,396 women. Baseline HPV, cytology and p16 results were compared across histological categories. Diagnostic performance for CIN2 + and CIN3 + was assessed for individual tests and simulated combined triage strategies. Among HPV-positive women with eligible one-year follow-up, histologically confirmed CIN2 + was analysed as the primary clinical follow-up endpoint, while persistent HPV positivity, ASC-US+ cytology and repeat p16 positivity were analysed as secondary follow-up endpoints. Bias-reduced multivariable logistic regression was used to evaluate the association between baseline p16 status and one-year CIN2 + detection. p16 positivity increased with histological severity, from 19.28% in women with normal histology to 87.07% in CIN2, 94.44% in CIN3 and 100.00% in cervical cancer. For CIN3 + detection, p16 positivity had sensitivity comparable to ASC-US+ cytology (94.99% vs. 94.15%) but higher specificity (52.23% vs. 37.90%). In simulated triage analyses, HPV16/18 positivity or p16 positivity reduced the referral rate compared with HPV16/18 positivity or ASC-US+ cytology (57.97% vs. 69.95%) while maintaining similar CIN3 + sensitivity (95.82% vs. 96.10%). Among HPV-positive women, immediate CIN3 + risk was 32.94% in p16-positive women and 3.33% in p16-negative women. At one year, CIN2 + was detected in 5.3% of baseline p16-positive women and 1.7% of p16-negative women. After adjustment for age, HPV16/18 positivity, baseline ASC-US+ cytology and baseline CIN1 histology, baseline p16 positivity remained associated with one-year CIN2 + detection (adjusted OR 9.53, 95% CI 3.80-23.95, P < 0.001). Baseline p16-positive women also had lower HPV clearance and higher rates of persistent HPV positivity, ASC-US+ cytology and repeat p16 positivity. In this retrospective screening cohort, baseline p16 status was associated with histological severity, immediate CIN2+/CIN3 + risk and one-year CIN2 + detection. Persistent HPV positivity, ASC-US+ cytology and repeat p16 positivity were more frequent in p16-positive women. p16 may improve risk stratification among HPV-positive women in this setting, particularly those with NILM cytology or non-16/18 hrHPV infection. Longer prospective follow-up is needed to validate its role in risk-based screening management.