TY - JOUR
T1 - Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years
T2 - results at recruitment for a randomised controlled trial
AU - Ronco, Guglielmo
AU - Giorgi-Rossi, Paolo
AU - Carozzi, Francesca
AU - Dalla Palma, Paolo
AU - Del Mistro, Annarosa
AU - De Marco, Laura
AU - De Lillo, Margherita
AU - Naldoni, Carlo
AU - Pierotti, Paola
AU - Rizzolo, Raffaella
AU - Segnan, Nereo
AU - Schincaglia, Patrizia
AU - Zorzi, Manuel
AU - Confortini, Massimo
AU - Cuzick, Jack
PY - 2006/7
Y1 - 2006/7
N2 - 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 ≥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. Findings: 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 (≥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]). Interpretation: 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.
AB - 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 ≥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. Findings: 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 (≥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]). Interpretation: 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.
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U2 - 10.1016/S1470-2045(06)70731-8
DO - 10.1016/S1470-2045(06)70731-8
M3 - Article
C2 - 16814206
AN - SCOPUS:33745278233
VL - 7
SP - 547
EP - 555
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 7
ER -