HPV Integration as a Triage Tool for HPV-Positive Women in Cervical Cancer Screening

Effective triage of HPV-positive women remains challenging, as conventional cytology often yields excessive colposcopy referrals due to limited specificity. We evaluated HPV integration status-a key molecular marker associated with cervical carcinogenesis-as a novel triage biomarker within the Fujian-Hubei Screening Cohort (N=31,628). Among 949 prospectively enrolled HPV-positive women with concurrent HPV integration testing (HIVID), genotyping, and cytology, HPV integration emerged as the strongest independent predictor of CIN3+ (aOR = 68.1). As a standalone triage tool, HPV integration detection significantly outperformed cytology, demonstrating superior specificity (97.0% vs. 64.3%; p<0.001) and PPV (57.1% vs. 10.4%; p<0.001) while maintaining comparable sensitivity (66.7% vs. 68.5%). Critically, our combined strategy integrating HPV16/18 genotyping with integration detection achieved optimized performance: it enhanced specificity by 25.2% (69.5% vs. 44.3%) and yielded a higher PPV (14.7% vs. 9.1%) compared to standard cytology+genotyping, with no significant sensitivity loss (87.0% vs. 92.6%; p=0.526). This approach identified a large low-risk subgroup (NILM/integration-negative; 59.2% of cohort) with minimal CIN3+ risk (0.7%), enabling an 82% reduction in colposcopy referrals versus cytology triage (6.6% vs. 37.6%; p<0.001). These results position HPV integration as a robust biomarker for precision risk stratification. The combined use of HPV genotyping and integration detection offers an efficient, clinically actionable strategy to minimize unnecessary procedures while maintaining high-grade lesion detection.