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Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial

BMJ 2007; 335 doi: (Published 05 July 2007) Cite this as: BMJ 2007;335:28
  1. Guglielmo Ronco, responsible, Cervical Screening Evaluation Unit1,
  2. Jack Cuzick, director12,
  3. Paola Pierotti, senior biologist8,
  4. Maria Paola Cariaggi, director, Unit of Cytopathology3,
  5. Paolo Dalla Palma, director, Unit of Pathology4,
  6. Carlo Naldoni, coordinator regional cancer screening programmes7,
  7. Bruno Ghiringhello, director, Unit of Pathology2,
  8. Paolo Giorgi-Rossi, responsible10,
  9. Daria Minucci, director6,
  10. Franca Parisio, senior biologist2,
  11. Ada Pojer, senior biologist4,
  12. Maria Luisa Schiboni, senior biologist11,
  13. Catia Sintoni, senior biologist9,
  14. Manuel Zorzi, epidemiologist5,
  15. Nereo Segnan, director1,
  16. Massimo Confortini, director, Unit of Analytic and Biomolecular Cytology3
  1. 1Unit of Cancer Epidemiology, Centre for Cancer Prevention, Via S Francesco da Paola 31 10123 Turin, Italy
  2. 2S Anna Hospital, Turin, Italy
  3. 3Scientific Institute for Cancer Prevention of Tuscany Region, Florence, Italy
  4. 4S Chiara Hospital, Trento, Italy
  5. 5Venetian Tumour Registry, Istituto Oncologico Veneto, Padua, Italy
  6. 6Unit of Obstetrics and Gynaecology, University Hospital, Padua, Italy
  7. 7Emilia-Romagna Region, Bologna, Italy
  8. 8Maggiore Hospital, AUSL Bologna, Italy
  9. 9S Maria delle Croci Hospital, Ravenna, Italy
  10. 10Health Technologies Unit, Agency for Public Health Lazio Region, Rome, Italy
  11. 11S Giovanni Hospital, Rome, Italy
  12. 12Cancer Research UK Clinical Centre, Epidemiology, Mathematics and Statistics, Queen Mary's School of Medicine and Dentistry, London
  1. Correspondence to: G Ronco guglielmo.ronco{at}
  • Accepted 1 April 2007


Objective To compare the accuracy of conventional cytology with liquid based cytology for primary screening of cervical cancer.

Design Randomised controlled trial.

Setting Nine screening programmes in Italy.

Participants Women aged 25-60 attending for a new screening round: 22 466 were assigned to the conventional arm and 22 708 were assigned to the experimental arm.

Interventions Conventional cytology compared with liquid based cytology and testing for human papillomavirus.

Main outcome measure Relative sensitivity for cervical intraepithelial neoplasia of grade 2 or more at blindly reviewed histology, with atypical cells of undetermined significance or more severe cytology considered a positive result.

Results In an intention to screen analysis liquid based cytology showed no significant increase in sensitivity for cervical intraepithelial neoplasia of grade 2 or more (relative sensitivity 1.17, 95% confidence interval 0.87 to 1.56) whereas the positive predictive value was reduced (relative positive predictive value v conventional cytology 0.58, 0.44 to 0.77). Liquid based cytology detected more lesions of grade 1 or more (relative sensitivity 1.68, 1.40 to 2.02), with a larger increase among women aged 25-34 (P for heterogeneity 0.0006), but did not detect more lesions of grade 3 or more (relative sensitivity 0.84, 0.56 to 1.25). Results were similar when only low grade intraepithelial lesions or more severe cytology were considered a positive result. No evidence was found of heterogeneity between centres or of improvement with increasing time from start of the study. The relative frequency of women with at least one unsatisfactory result was lower with liquid based cytology (0.62, 0.56 to 0.69).

Conclusion Liquid based cytology showed no statistically significant difference in sensitivity to conventional cytology for detection of cervical intraepithelial neoplasia of grade 2 or more. More positive results were found, however, leading to a lower positive predictive value. A large reduction in unsatisfactory smears was evident.

Trial registration Current Controlled Trials ISRCTN81678807.


  • We thank the staff who helped with the study and the women who participated in this study.

  • Contributors: GR was the project leader and is guarantor. GR designed the study with NS and JC. GR, MPC, and JC drafted the manuscript. GR, PG-R, and MPC were responsible for data analysis. PDP, MPC, DM, FP, AP, MLS, and CS were locally responsible for preparation and interpretation of slides produced after liquid based cytology. MC and BG supervised the quality assurance for cytology interpretation. PDP and BG coordinated the review of histology. MC, PDP, PG-R, CN, and MZ organised the local fieldwork. All authors critically revised the manuscript. In addition to the authors the following are contributing members of the New Technologies for Cervical Cancer Screening (NTCC) Working Group—Turin: R Rizzolo, D Mari, P Giubilato (CPO Piemonte), A Gillio-Tos, L De Marco (Unit of Cancer Epidemiology and CPO, CERMS, University of Turin), R Volante (Centre for early cancer diagnosis and treatment, OIRM S Anna), E Berardengo (Unit of Pathology, Ospedale S Giovanni AS), A Andrion (Unit of Pathology, Ospedale Martini), S Coverlizza (Unit of Pathology, Ospedale Giovanni Bosco), S Taraglio (Unit of Pathology, Ospedale Maria Vittoria), and MG Accinelli (Unit of Pathology, University of Turin). Trento: E Polla, S Girlando, and D Aldovini (Unit of Pathology, Ospedale di Trento); Veneto: M Vettorazzi (Venetian Tumour Registry, Istituto Oncologico Veneto), A Del Mistro (Istituto Oncologico Veneto, Padua), M Matteucci (Unity of Gynaecology, Azienda Ospedaliera di Padova), L Onnis, E Insacco (Department of Pathology, University of Padua), M Lestani (Department of Pathology, University of Verona), and A Vignato (Servizio di Citologia, Ostetricia e Ginecologia, Ospedale di Soave); Emilia-Romagna: M Manfredi (Centro screening, AUSL Bologna), GP Casadei (Unit of Pathology, Ospedale Maggiore, AUSL Bologna), G Collina (Unit of Pathology Ospedale Bellaria, AUSL Bologna), M Serafini, P Schincaglia, B Vitali (Centro Prevenzione Oncologica, AUSL Ravenna), M Aldi (Unit of Pathology, Presidio Ospedaliero di Faenza, AUSL Ravenna), and S Folicaldi, R Nannini, G Galanti, and M De Lillo (Unit of Pathology, Presidio Ospedaliero, AUSL di Imola); Florence: M Zappa, A Iossa, S Ciatto, S Cecchini, C Sani, F Carozzi (CSPO Firenze), and GL Taddei (Unit of Pathology University of Florence); Lazio: S Brezzi, P Raggi, and E Gomes (Local Health Unit, Viterbo, Italy), and A Pellegrini (Ospedale S Giovanni, Rome).

  • Funding: European Union (Europe against cancer contracts SI.2.327046 and SPC.2002475), Italian Ministry of Health (applied research projects and L 138/ 2004), Compagnia di S Paolo FIRMS, Regione Piemonte, Regione Toscana, Regione Veneto, Regione Emilia-Romagna, Agenzia di Sanità Pubblica, Regione Lazio. Funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests: JC is a member of the speaker's bureau for Digene. His institution (Cancer Research UK) has received research funding from Roche Diagnostics for a different study. MC is the principal recipient of a grant to the Scientific Institute for Cancer Prevention of Tuscany Region from Menarini Diagnostics. This grant is for another study.

  • Ethical approval: This study was approved by the local research ethics committees of the participating centres.

  • Accepted 1 April 2007
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