title: Evaluation of Viral Load as a Triage Strategy With Primary High-Risk Human Papillomavirus Cervical Cancer Screening.
abstract: OBJECTIVE
  The aim of the study was to evaluate the human papillomavirus (HPV) viral load combined with cytology as a secondary screening strategy after primary HPV screening.
  
  
  METHODS
  The data referring to direct Hybrid Capture 2 (HC2), cytology, and histology from Shenzhen Cervical Cancer Screening Trial II were re-analyzed to determine the correlation between viral load and cervical lesions. In addition, algorithms using different viral loads as cut points for immediate colposcopy plus cytology triage were compared with several recommended or controversial primary screening methods.
  
  
  RESULTS
  A total of 8,556 women with a mean age of 38.9 years were included in the analysis, of which 13.67% tested high-risk HPV positive with a prevalence of 2.72% for cervical intraepithelial neoplasia 2+ (CIN 2+) and 1.65% for CIN 3+. A significant correlation was observed between increasing relative light units/control (RLU/CO) values and worsening cervical lesions. The mean RLU/CO values for negative, CIN 1, CIN 2, CIN 3, and cancer were 6.86, 119.43, 410.90, 449.39, and 853.26, respectively. A larger proportion of HPV infections with relative high viral load (≥10 RLU/CO) were found in higher-grade lesions. The algorithm using 10 or greater RLU/CO as cut point for immediate colposcopy followed by triage cytology for the other positive (≥1 < 10 RLU/CO) had sensitivity of 93.13%/96.45% and specificity of 92.32%/91.44% for CIN 2+/3+, and the colposcopy referral rate was 10.00%.
  
  
  CONCLUSIONS
  Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.
authors.affiliation: 1Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, PR China; 2Shenzhen Technical Research and Development Center on Gynecoligic Oncology, Shenzhen, PR China; 3Gynecologic Oncology Division, Women's Health Institute, Cleveland Clinic, Cleveland, OH; 4Preventive Oncology International, Cleveland Heights, OH; and 5Department of Obstetrics and Gynecology, Kaiser Permanente, Fontana, CA.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Luo
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Belinson
authors.forename: Hui
authors.initials: H
authors.lastname: Du
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Qu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Pretorius
authors.forename: Ruifang
authors.initials: R
authors.lastname: Wu
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D003584:Cytological Techniques; D003955:Diagnostic Tests, Routine / Q000379:methods*; D019468:Disease Management; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D019562:Viral Load