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Six-Year Regression and Progression of Cervical Lesions of Different Human Papillomavirus Viral Loads in Varied Histological Diagnoses
  1. Shao-Ming Wang, MD*,
  2. Danny Colombara, MPH*,,
  3. Ju-Fang Shi, MD, PhD,
  4. Fang-Hui Zhao, MD, PhD*,
  5. Jing Li, MD, PhD*,
  6. Feng Chen, BS*,
  7. Wen Chen, MD, PhD*,
  8. Shu-Min Li, MD,
  9. Xun Zhang, MD,
  10. Qin-Jing Pan, MD,
  11. Jerome L. Belinson, MD§,
  12. Jennifer S. Smith, PhD and
  13. You-Lin Qiao, MD, PhD*
  1. *Department of Cancer Epidemiology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and
  2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA;
  3. Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;
  4. §Women’s Health Institute, Cleveland Clinic, Cleveland, OH; and
  5. Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
  1. Address correspondence and reprint requests to You-Lin Qiao, MD, PhD, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, 17 South Panjiayuan Lane, Chaoyang District, Beijing, 100021, China. E-mail: qiaoy@cicams.ac.cn.

Abstract

Objective This study aims to evaluate human papillomavirus (HPV) viral loads as a biomarker for triage into colposcopy and cervical intraepithelial neoplasia grade 2 (CIN2) therapy to reduce the colposcopy referral rate and CIN2 overtreatment in low-resource settings.

Methods In 1999, 1997 women aged 35 to 45 years in Shanxi, China, received 6 cervical screenings with pathological confirmation. In 2005, 1461 histologically normal women, 99 with CIN grade 1 (CIN1), and 30 with CIN2 or worse (CIN2+) were rescreened in a follow-up study. Human papillomavirus was detected by Hybrid Capture 2. Viral load, estimated by the ratio of relative light units to standard positive control (RLU/PC), was categorized into 4 groups: negative (<1.0), low (≥1.0, <10.0), moderate (≥10.0, <100.0), and high (≥100.0). We estimated the cumulative incidence of CIN2+ by viral load subgroups and calculated adjusted hazard ratios for CIN2+ using Cox proportional hazards regression.

Results Cumulative incidence of CIN2+ increased with baseline HPV viral loads among normal women and women with CIN1 at baseline (P -trend < 0.001). Repeat moderate-high viral load was associated with the highest risk for CIN2+ (adjusted hazard ratio, 188.8; 95% confidence interval, 41.2–864.1). Raising the ratio of relative light units to standard positive control cutoff from 1.0 to 10.0 for colposcopy greatly reduced the referral rate from 18.1% to 12.9%. It also increased the specificity (84.8% vs 90.4%), the positive predictive value (22.5% vs 28.9%), and the positive likelihood ratio (6.4 vs 8.9), yet with loss of sensitivity by 12% (97.6% vs 85.7%). Among women with CIN2 at baseline, 56% regressed to normal, 24% regressed to CIN1, 4% remained CIN2, and 16% progressed to CIN grade 3 or worse.

Conclusions Locales using HPV testing as the primary screening method and lacking high-quality cytology-based screening should consider viral load as an alternative to colposcopy triage for women older than 35 years. Viral loads may also predict CIN2 progression until additional biomarkers become available.

  • Cervical intraepithelial neoplasia
  • Hazard ratios
  • Human papillomavirus viral load
  • Regression
  • Progression

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Footnotes

  • This work was supported by the Specialized Research Fund for the Doctoral Program of Higher Education (China MOE 20030023014), the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988 to S.-M.W. and D.C.), the National Cancer Institute (R25 CA94880 to D.C.), and the American Relief and Recovery Act.

  • The authors declare no conflicts of interest.

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