title: Cervical Precancer and Cancer Risk by Human Papillomavirus Status and Cytologic Interpretation: Implications for Risk-Based Management.
abstract: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (≥CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management.
  
  
  
  Women aged ≥25 years (n = 7,823) underwent high-risk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without ≥CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year ≥CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results.
  
  
  
  One-year ≥CIN3 risks ranged from 81.27% (95% CI, 66.02%-90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%-0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year ≥CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%-17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%-10.37%; P = 0.002) and similar to hrHPV-positive/LSIL (11.45%; 95% CI, 8.61%-15.07%; P = 0.3). Three-year ≥CIN3 risks for HPV16 positive/LSIL and HPV16/atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%-35.58%) and 24.36% (95% CI, 15.86%-35.50%), respectively, and 0.72% (95% CI, 0.45%-1.14%) for hrHPV negative/NILM.
  
  
  
  hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider.
  
  
  
  These results provide relevant benchmarks for risk-based cervical cancer screening and management. Cancer Epidemiol Biomarkers Prev; 25(12); 1595-9. ©2016 AACR.
authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. philip.castle@einstein.yu.edu.|Global Coalition Against Cervical Cancer, Arlington, Virginia.
authors: Philip E
authors: PE
authors: Castle
authors: Roche Molecular Systems, Pleasanton, California.
authors: Shagufta
authors: S
authors: Aslam
authors: Roche Molecular Systems, Pleasanton, California.
authors: Catherine
authors: C
authors: Behrens
mesh_terms: D000328:Adult; D065309:Atypical Squamous Cells of the Cervix; D001706:Biopsy; D003127:Colposcopy; D019468:Disease Management; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D018570:Risk Assessment; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology