Zhang, Junji, Zhao, Yuqian, Dai, Yi, Dang, Le, Ma, Li, Yang, Chunxia, Li, Yang, Kong, Linghua, Wei, Lihui, Zhang, Shulan, Liu, Jihong, Xi, Minrong, Chen, Long, Duan, Xianzhi, Xiao, Qing, Abulizi, Guzhalinuer, Zhang, Guonan, Hong, Ying, Gao, Xiaohong, Zhou, Qi, Xie, Xing, Li, Li, Niyazi, Mayinuer, Zhang, Zhifen, Tuo, Jiyu, Ding, Yiling, Si, Manfei, Chen, Fei, Song, Li, Qiao, Youlin, and Lang, Jinghe
Key Points Question Does integration of high-risk human papillomavirus (hrHPV) testing into China’s national screening program lead to better outcomes than current primary screening approaches? Findings In this randomized clinical trial that included 60 732 women, hrHPV testing as primary screening provided a 2.0-fold to 2.7-fold yield for cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse compared with cytology or visual inspection with acetic acid and Lugol iodine at baseline. It also resulted in a significantly lower risk of cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse for baseline-negative women under routine conditions in primary health care settings in rural areas across China. Meaning It is reasonable to incorporate hrHPV testing (polymerase chain reaction–based testing for urban areas, hybrid capture–based testing for rural areas) as a primary screening method into China’s current national screening program., This randomized clinical trial compares the results of high-risk human papillomavirus testing vs current primary screening approaches, assessing screening performance, cost-effectiveness, and service system capacity within China’s national cervical cancer screening program., Importance Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China’s national cervical cancer screening program. Objective To evaluate hrHPV testing as a new screening modality for the national program. Design, Setting, and Participants This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated. Interventions At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. Main Outcomes and Measures The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. Results A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. Conclusions and Relevance In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction–based for urban areas, hybrid capture-based for rural areas) into China’s national screening program is reasonable. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR1900022530