Junji Zhang1, Yuqian Zhao2,3, Yi Dai1, Le Dang3, Li Ma4, Chunxia Yang5, Yang Li6, Linghua Kong1, Lihui Wei7, Shulan Zhang8, Jihong Liu9, Minrong Xi10, Long Chen11, Xianzhi Duan12, Qing Xiao13, Guzhalinuer Abulizi14, Guonan Zhang2, Ying Hong15, Xiaohong Gao4, Qi Zhou16, Xing Xie17, Li Li18, Mayinuer Niyazi19, Zhifen Zhang20, Jiyu Tuo21, Yiling Ding22, Manfei Si1, Fei Chen1, Li Song23, Youlin Qiao3, Jinghe Lang1. 1. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. 2. Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science & Technology of China, Chengdu, China. 3. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Dalian Medical University, Dalian, China. 5. West China School of Public Health, Sichuan University, Chengdu, China. 6. Institute of Medical Information, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China. 7. Peking University People's Hospital, Beijing, China. 8. China Medical University, Shenyang, China. 9. Sun Yat-sen University Cancer Center, Guangzhou, China. 10. West China Second University Hospital, Sichuan University, Chengdu, China. 11. Qingdao Municipal Hospital, Qingdao, China. 12. Beijing Tongren Hospital, Capital Medical University, Beijing, China. 13. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. 14. Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China. 15. Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. 16. Chongqing University Cancer Hospital, Chongqing, China. 17. Women's Hospital School of Medicine Zhejiang University, Hangzhou, China. 18. Tumor Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China. 19. People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China. 20. Hangzhou Women's Hospital, Hangzhou, China. 21. Hubei Cancer Hospital, Wuhan, China. 22. The Second Xiangya Hospital of Central South University, Changsha, China. 23. Department of Women and Child Health, National Health Commission of China, Beijing, China.
Abstract
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.
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.
Authors: Shang-Ying Hu; Aimée R Kreimer; Carolina Porras; Diego Guillén; Mario Alfaro; Teresa M Darragh; Mark H Stoler; Luis F Villegas; Rebecca Ocampo; Ana Cecilia Rodriguez; Mark Schiffman; Sabrina H Tsang; Douglas R Lowy; John T Schiller; John Schussler; Wim Quint; Mitchell H Gail; Joshua N Sampson; Allan Hildesheim; Rolando Herrero Journal: J Natl Cancer Inst Date: 2022-09-09 Impact factor: 11.816
Authors: Mohamed S Bangura; Yuqian Zhao; Maria Jose Gonzalez Mendez; Yixuan Wang; Salah Didier Sama; Kunpeng Xu; Ran Ren; Li Ma; You-Lin Qiao Journal: Front Med (Lausanne) Date: 2022-09-15