Six-Year Regression and Progression of Cervical Lesions of Different Human Papillomavirus Viral Loads in Varied Histological Diagnoses. Issue 4 (1st May 2013)

• Record Type: Journal Article
• Authors: Wang, Shao-Ming; Colombara, Danny; Shi, Ju-Fang; Zhao, Fang-Hui; Li, Jing; Chen, Feng; Chen, Wen; Li, Shu-Min; Zhang, Xun; Pan, Qin-Jing; Belinson, Jerome L.; Smith, Jennifer S.; Qiao, You-Lin
• Is Part Of: International journal of gynecological cancer. Volume 23:Issue 4(2013)
• Page Start: 716
• Page End: 723
• Publication Date: 2013-05-01
• Subjects: Cervical intraepithelial neoplasia -- Hazard ratios -- Human papillomavirus viral load -- Regression -- Progression; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0b013e318286a95d
• Languages: English
• ISSNs: 1048-891X

Abstract

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.