title: Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.
abstract: BACKGROUND
  Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results.
  
  
  METHODS
  In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated.
  
  
  RESULTS
  The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82).
  
  
  CONCLUSIONS
  HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.
authors.affiliation: Unit of Cancer Epidemiology, Centro per la Prevenzione Oncologica Piemonte, 10123 Turin, Italy. guglielmo.ronco@cpo.it
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Ronco
authors.forename: Nereo
authors.initials: N
authors.lastname: Segnan
authors.forename: Paolo
authors.initials: P
authors.lastname: Giorgi-Rossi
authors.forename: Marco
authors.initials: M
authors.lastname: Zappa
authors.forename: Gian Piero
authors.initials: GP
authors.lastname: Casadei
authors.forename: Francesca
authors.initials: F
authors.lastname: Carozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Dalla Palma
authors.forename: Annarosa
authors.initials: A
authors.lastname: Del Mistro
authors.forename: Stefania
authors.initials: S
authors.lastname: Folicaldi
authors.forename: Anna
authors.initials: A
authors.lastname: Gillio-Tos
authors.forename: Gaetano
authors.initials: G
authors.lastname: Nardo
authors.forename: Carlo
authors.initials: C
authors.lastname: Naldoni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Schincaglia
authors.forename: Manuel
authors.initials: M
authors.lastname: Zorzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Confortini
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D000328:Adult; D003127:Colposcopy; D003584:Cytological Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D007558:Italy; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D011237:Predictive Value of Tests; D012017:Referral and Consultation; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology