Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.
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.
Ronco
Guglielmo
G
Unit of Cancer Epidemiology, Centro per la Prevenzione Oncologica Piemonte, 10123 Turin, Italy. guglielmo.ronco@cpo.it
Segnan
Nereo
N
Giorgi-Rossi
Paolo
P
Zappa
Marco
M
Casadei
Gian Piero
GP
Carozzi
Francesca
F
Dalla Palma
Paolo
P
Del Mistro
Annarosa
A
Folicaldi
Stefania
S
Gillio-Tos
Anna
A
Nardo
Gaetano
G
Naldoni
Carlo
C
Schincaglia
Patrizia
P
Zorzi
Manuel
M
Confortini
Massimo
M
Cuzick
Jack
J
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