Lower cost strategies for triage of human papillomavirus DNA-positive women

Int J Cancer. 2014 Jun 15;134(12):2891-901. doi: 10.1002/ijc.28616. Epub 2013 Dec 3.

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+.

Keywords: E6; HPV; careHPV; cervical cancer; developing countries; triage.

MeSH terms

  • Adult
  • Aged
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / virology
  • China
  • Colposcopy
  • DNA, Viral / analysis
  • DNA-Binding Proteins / analysis
  • Early Detection of Cancer / economics
  • Female
  • Human Papillomavirus DNA Tests / economics
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • Mass Screening / economics
  • Middle Aged
  • Oncogene Proteins, Viral / analysis
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / virology
  • Precancerous Conditions / diagnosis*
  • Precancerous Conditions / virology
  • Repressor Proteins / analysis
  • Sensitivity and Specificity
  • Triage / economics*
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • DNA, Viral
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Repressor Proteins