Clinical performance of a genotyping assay based on a hybrid capture technique in cervical cancer screening in China: a prospective population-based multicentre cohort study.

Objectives: We aimed to assess the clinical performance of DH3, a hybrid capture assay that separately detects human papillomavirus (HPV) 16/18 and 12 other HPV types, for primary screening for cervical cancer in the general population, following Chinese guidelines.

Methods: A total of 9379 eligible women aged 21 to 64 years from three centres underwent baseline screening with DH3 and liquid-based cytology (LBC), and were subsequently followed for 3 years. The diagnostic performance of HPV testing (DH3) and LBC-including sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value-was evaluated for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions.

Results: At baseline, 146 (1.56%) participants were identified with CIN2+ lesions. Compared with LBC with reflex high-risk HPV (HR-HPV), primary HR-HPV with reflex LBC showed a significantly higher sensitivity (95.89% [95% CI: 91.33%-98.10%] vs. 84.93% [95% CI: 78.24%-89.83%], P = 0.004), and a marginally lower specificity (89.65% [95% CI: 89.01%-90.25%] vs. 91.61% [95% CI: 91.02%-92.15%], P <0.001) for detecting CIN2+. 7747 (82.6% follow-up rate) women completed the 3-year follow-up, during which 236 (3.00%) were cumulatively diagnosed with CIN2+. HR-HPV with reflex LBC demonstrated significantly higher sensitivity than LBC with reflex HR-HPV (91.95% [95% CI: 87.77%-94.79%] vs. 63.56% [95% CI: 57.25%-59.44%], P <0.001), whereas both methods exhibited similar specificity (90.57% [95% CI: 89.89%-91.21%] vs. 91.37% [95% CI: 90.72%-91.99%], P = 0.062) for CIN2+. The colposcopy referral rates for the two algorithms were also comparable (5.77% (447/7747) vs. 5.38% (417/7747), p 0.294). In addition, individuals positive for HPV16/18 had a 3-year absolute risk of CIN2+ exceeding 48%. In comparison, the risk was only 0.28% (19/6822) in the HPV-negative population, markedly >1.24% (86/6949) risk observed in individuals with normal cytology. Limiting the analysis to women aged ≥30 yielded similar results.

Discussion: Our study indicates that DH3 exhibits dependable clinical performance in cervical screening. The validated HPV test is expected to enhance the quality of population-based screening.