TY - JOUR
T1 - Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China
T2 - A Multicenter, Open-label, Randomized Clinical Trial
AU - Zhang, Junji
AU - Zhao, Yuqian
AU - Dai, Yi
AU - Dang, Le
AU - Ma, Li
AU - Yang, Chunxia
AU - Li, Yang
AU - Kong, Linghua
AU - Wei, Lihui
AU - Zhang, Shulan
AU - Liu, Jihong
AU - Xi, Minrong
AU - Chen, Long
AU - Duan, Xianzhi
AU - Xiao, Qing
AU - Abulizi, Guzhalinuer
AU - Zhang, Guonan
AU - Hong, Ying
AU - Gao, Xiaohong
AU - Zhou, Qi
AU - Xie, Xing
AU - Li, Li
AU - Niyazi, Mayinuer
AU - Zhang, Zhifen
AU - Tuo, Jiyu
AU - Ding, Yiling
AU - Si, Manfei
AU - Chen, Fei
AU - Song, Li
AU - Qiao, Youlin
AU - Lang, Jinghe
N1 - Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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 60732 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 60732 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 18176 to hrHPV genotyping; among rural women, 11136 were randomized to VIA/VILI, 7080 to cytology, and 15385 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.
AB - 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 60732 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 60732 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 18176 to hrHPV genotyping; among rural women, 11136 were randomized to VIA/VILI, 7080 to cytology, and 15385 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.
UR - http://www.scopus.com/inward/record.url?scp=85098716501&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2020.6575
DO - 10.1001/jamaoncol.2020.6575
M3 - Article
C2 - 33377903
AN - SCOPUS:85098716501
SN - 2374-2437
VL - 7
SP - 263
EP - 270
JO - JAMA Oncology
JF - JAMA Oncology
IS - 2
ER -