Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study

Objectives The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. Methods 9829 eligible women aged 21-64 years from Henan, Shanxi and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for three-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. Results At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI: 91.34–99.31%] vs. 62/80, 77.50% [67.21–85.27%], PMcNemar<0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80–88.12%] vs. 8900/9749, 91.29% [90.72–91.83%], PMcNemar<0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91–96.39%] vs. 87/172, 50.58% [43.18–57.96%], PMcNemar<0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72–89.16%] vs. 6933/7660, 90.51% [89.83–91.15], PMcNemar<0.001). In addition, the absolute three-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), while the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy (NILM) population (1.21%, 85/7018). Moreover, similar results were found in women ≥ 30 years old. Conclusions The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.