title: Lower cost strategies for triage of human papillomavirus DNA-positive women.
abstract: Using human papillomavirus (HPV) testing for cervical cancer screening in lower-resource settings (LRS) will result in a significant number of screen-positive women. This analysis compares different triage strategies for detecting cervical precancer and cancer among HPV-positive women in LRS. This was a population-based study of women aged 25-65 years living in China (n = 7,541). Each woman provided a self-collected and two clinician-collected specimens. The self-collected and one clinician-collected specimen were tested by two HPV DNA tests-careHPV™ and Hybrid Capture 2; the other clinician-collected specimen was tested for HPV16/18/45 E6 protein. CareHPV™-positive specimens were tested for HPV16/18/45 DNA. HPV DNA-positive women underwent visual inspection with acetic acid (VIA) and then colposcopic evaluation with biopsies. The performance for detection of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) among HPV DNA-positive women was assessed for different triage strategies: HPV16/18/45 E6 or DNA detection, VIA, colposcopic impression, or higher signal strength (≥10 relative light units/positive control [rlu/pc]). The percent triage positive ranges were 14.8-17.4% for VIA, 17.8-20.9% for an abnormal colposcopic impression; 7.9-10.5% for HPV16/18/45 E6; 23.4-28.4% for HPV16/18/45 DNA; and 48.0-62.6% for higher signal strength (≥10 rlu/pc), depending on the HPV test/specimen combination. The positivity for all triage tests increased with severity of diagnosis. HPV16/18/45 DNA detection was approximately 70% sensitive and had positive predictive values (PPV) of approximately 25% for CIN3+. HPV16/18/45 E6 detection was approximately 50% sensitive with a PPV of nearly 50% for CIN3+. Different triage strategies for HPV DNA-positive women provide important tradeoffs in colposcopy or treatment referral percentages and sensitivity for prevalent CIN3+.
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: Jose
authors.initials: J
authors.lastname: Jeronimo
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Zhao
authors.forename: Johannes
authors.initials: J
authors.lastname: Schweizer
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Melissa
authors.initials: M
authors.lastname: Valdez
authors.forename: Peter
authors.initials: P
authors.lastname: Lu
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Le-Ni
authors.initials: LN
authors.lastname: Kang
authors.forename: Pooja
authors.initials: P
authors.lastname: Bansil
authors.forename: Proma
authors.initials: P
authors.lastname: Paul
authors.forename: Charles
authors.initials: C
authors.lastname: Mahoney
authors.forename: Marthe
authors.initials: M
authors.lastname: Berard-Bergery
authors.forename: Ping
authors.initials: P
authors.lastname: Bai
authors.forename: Roger
authors.initials: R
authors.lastname: Peck
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Stoler
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
mesh_terms: D000328:Adult; D000368:Aged; D002681:China; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D055088:Early Detection of Cancer / Q000191:economics; D005260:Female; D061809:Human Papillomavirus DNA Tests / Q000191:economics; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D008403:Mass Screening / Q000191:economics; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000821:virology; D012097:Repressor Proteins / Q000032:analysis; D012680:Sensitivity and Specificity; D014218:Triage / Q000191:economics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000517:prevention & control / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins
keywords: E6; HPV; careHPV; cervical cancer; developing countries; triage