# HPV testing with 16/18 genotyping for risk stratification among women with normal cytology: a multicenter prospective cohort study from China

## TL;DR

This study shows that HPV testing with genotyping for HPV 16/18 helps identify women at higher risk of cervical cancer, even when their initial cell tests are normal.

## Contribution

The study provides large-scale evidence supporting the integration of HBRT-H14 HPV testing with 16/18 genotyping into cervical cancer screening pathways.

## Key findings

- HPV 16/18 positivity was associated with a 20.9% three-year risk of CIN2+, compared to 0.1% for HPV-negative women.
- HBRT-H14 demonstrated high sensitivity (92.3%) and specificity (89.6%) for detecting CIN2+.
- HPV 16/18 genotyping effectively stratified risk among women with normal cytology.

## Abstract

To evaluate the clinical performance of Hybribio’s 14-type HPV real-time PCR with 16/18 genotyping (HBRT-H14) and its risk stratification utility among women with normal cytology (NILM). From 2017 to 2020, a multicenter cohort enrolled 8,401 women aged 30–64 years with NILM cytology. Baseline HPV testing used HBRT-H14. Women positive for HPV 16/18 were referred for colposcopy; follow-up was annual for 3 years or until the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Analyses included 6,679 women who completed follow-up. Overall HPV positivity was 11.4%, including 2.3% HPV 16/18. Over 3 years, sensitivity and specificity of HPV positivity for CIN2+ were 92.3% (95% confidence interval [CI]: 84.2–96.4) and 89.6% (88.8–90.3). For HPV 16/18 positivity, sensitivity and specificity were 41.0% (30.8–52.1) and 98.2% (97.8–98.5). Three-year cumulative CIN2+ risk was 20.9% (15.2–28.1) for HPV 16/18-positive women, 6.6% (4.9–8.9) for other types, and 0.1% (0.04–0.2) for HPV-negative women. HBRT-H14 shows strong clinical performance for detecting CIN2+, and HPV 16/18 genotyping provides effective risk stratification among women with NILM cytology. Findings support integration of HBRT-H14 into HPV-based screening pathways with HPV 16/18 genotyping and cytology triage of other types.

This multicenter prospective study evaluated the Hybribio 14 high-risk HPV real-time PCR assay (HBRT-H14) in 8,401 women with normal (NILM) cytology under guideline-based follow-up. The assay showed high clinical sensitivity and a very low risk among HPV-negative women, and HPV 16/18 genotyping provided clear risk stratification. These findings deliver large-scale, practice-oriented evidence supporting integration of HBRT-H14 into HPV-based screening pathways that use HPV 16/18 genotyping with cytology triage of other types.