title: Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.
abstract: BACKGROUND
  A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US.
  
  
  METHODS
  During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +.
  
  
  RESULTS
  Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women.
  
  
  CONCLUSIONS
  Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, Av, Gran Vía, 199-203L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ibáñez
authors.forename: Judit
authors.initials: J
authors.lastname: Moreno-Crespi
authors.forename: Montserrat
authors.initials: M
authors.lastname: Sardà
authors.forename: Josefina
authors.initials: J
authors.lastname: Autonell
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fibla
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: María
authors.initials: M
authors.lastname: Alejo
authors.forename: Isabel
authors.initials: I
authors.lastname: Català
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
authors.forename: Miquel
authors.initials: M
authors.lastname: Casas
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
mesh_terms: D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013030:Spain; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: D004279:DNA, Viral