Objective:

To assess the triage performance of extended HPV genotyping among HPV-positive women using data from five large, population-based cohort screening studies conducted across seven regions of China.

Approach:

• Data Collection: Investigators pooled data from 116,042 women aged 25–64 who participated in five cervical cancer screening projects. The analysis was restricted to high-risk HPV genotyping results from self-collected specimens; 7,821 HPV-positive women had complete HPV, cytology, and pathological data for the triage analysis.
• Analysis Methodology: Uniform eligibility criteria, pathological diagnostic standards, HPV genotype interpretation, and CIN3+ endpoint definitions were applied. Genotype-specific infection patterns and histologically confirmed cervical lesions were analyzed.
• Statistical Analysis: Receiver operating characteristic curve analyses compared the sensitivity and specificity of genotype- and cytology-based triage strategies. Binary logistic regression assessed whether coinfection modified genotype-specific CIN3+ risk.

Key Findings:

• HPV-16, HPV-52, HPV-58, HPV-51, and HPV-18 were the five most prevalent genotypes. Single HPV-16 infection had the highest CIN3+ rate.
• Cytology-free strategies targeting HPV-16/18/31/33/35/45/52/58 or HPV-16/18/31/33/52/58 had sensitivities of 97.7% and 97.3%, respectively, compared with 97.1% for standard HPV-16/18 plus cytology triage.
• The extended strategies had slightly lower specificity and produced modestly higher colposcopy referral rates than standard triage, but their diagnostic performance for CIN3+ detection was not significantly different.

Interpretation:

Extended HPV genotyping may provide a reproducible, cytology-free triage option for HPV-positive women, particularly in self-sampling programs. It could streamline screening and reduce dependence on operator-dependent cytology, although the modest increase in colposcopy referrals should be considered.

Limitations:

• Only 36 invasive cancer cases were detected, limiting assessment of genotype-specific cancer outcomes.
• Northeastern China was not represented, potentially limiting the national representativeness of the findings.
• The cross-sectional design could not evaluate longitudinal risk or determine the strategy’s ultimate effectiveness in preventing invasive cervical cancer.

Conclusion:

Extended HPV genotyping based on self-collected specimens maintained high sensitivity and specificity for CIN3+ detection without requiring cytology. The findings support it as a promising standalone triage alternative for HPV-positive women in population-based cervical cancer screening.