title: Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up.
abstract: OBJECTIVE
  To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction.
  
  
  METHODS
  Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated.
  
  
  RESULTS
  A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap.
  
  
  CONCLUSIONS
  HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older.
authors.affiliation: American Society for Clinical Pathology, 1225 New York Ave NW, Suite 350, Washington, DC 20005, USA. philip.castle@ascp.org
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Glass
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Rush
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Julia C
authors.initials: JC
authors.lastname: Gage
authors.forename: Julie
authors.initials: J
authors.lastname: Buckland
authors.forename: Greg
authors.initials: G
authors.lastname: Rydzak
authors.forename: Attila T
authors.initials: AT
authors.lastname: Lorincz
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006279:Health Maintenance Organizations; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009922:Oregon / Q000453:epidemiology; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D007507:Therapeutic Irrigation; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*
chemical_list: D004279:DNA, Viral