title: Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial.
abstract: BACKGROUND
  Testing for human papillomavirus (HPV) DNA is more sensitive but less specific than cytological analysis. Loss in specificity is most relevant in women younger than 35 years because of increased HPV prevalence. We aimed to compare conventional screening with an experimental strategy in women aged 25-34 years, and investigate the effect of different criteria of referral to define the best methods of HPV screening.
  
  
  METHODS
  Women were randomly assigned to the conventional procedure (standard cytology, with referral to colposcopy if cytology showed atypical squamous cells of undetermined significance or more [ASCUS+]) or an experimental procedure (liquid-based cytology and testing for high-risk HPV types, with referral to colposcopy with ASCUS+ cytology). Women positive for HPV (cutoff > or = 1 pg/mL) but with normal cytology were retested after 1 year. The main endpoint was the presence of cervical intraepithelial neoplasia at grade 2 or more (CIN2+) in reviewed histology. The main analysis was by intention to screen. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN81678807.
  
  
  RESULTS
  We randomly assigned 5808 women aged 25-34 years to the conventional group and 6002 to the experimental group. The experimental procedure was significantly more sensitive than the conventional procedure (55 vs 33 CIN2+ lesions detected; relative sensitivity 1.61 [95% CI 1.05-2.48]), but had a lower positive predictive value (PPV; relative PPV 0.55 [0.37-0.82]). HPV testing (> or = 1 pg/mL) with cytology triage was also more sensitive than conventional cytology (relative sensitivity 1.58 [1.03-2.44], relative PPV 0.78 [0.52-1.16]). Relative PPV could be improved, with minimum loss in sensitivity, by use of a 2 pg/mL cutoff for HPV testing. Compared with conventional cytology, liquid-based cytology had a relative sensitivity of 1.32 (0.84-2.06), relative PPV 0.58 [0.38-0.89]).
  
  
  CONCLUSIONS
  HPV testing alone with cytology triage could be a feasible alternative to conventional cytology for screening women younger than 35 years. Follow-up will provide data on possible overdiagnosis and on the feasibility of extended intervals.
authors.affiliation: Centre for Cancer Prevention (CPO), Turin, Italy. guglielmo.ronco@cpo.it
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Ronco
authors.forename: Paolo
authors.initials: P
authors.lastname: Giorgi-Rossi
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: Laura
authors.initials: L
authors.lastname: De Marco
authors.forename: Margherita
authors.initials: M
authors.lastname: De Lillo
authors.forename: Carlo
authors.initials: C
authors.lastname: Naldoni
authors.forename: Paola
authors.initials: P
authors.lastname: Pierotti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rizzolo
authors.forename: Nereo
authors.initials: N
authors.lastname: Segnan
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; D000367:Age Factors; D003127:Colposcopy; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D018579:Patient Selection; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology