A randomized crossover trial of PAPNET for primary cervical screening.
OBJECTIVE
To develop and demonstrate efficient methods to estimate the relative true positive and false positive rates of two cervical screening tests (conventional cytology and PAPNET).


METHODS
We designed the study to meet stringent methodologic criteria for comparison of two tests while simultaneously minimizing the numbers requiring reference standard verification. We used a cytology reference standard and also assessed histology when available. For the primary analysis, slides with discordant results around the test threshold (CIN 1) were reviewed by a panel of two cytopathologists, blind to previous results, to establish the reference standard result (reference standard threshold for abnormality CIN2). Where histology was available, a secondary analysis was conducted with the reference standard based on the highest grade lesion (either cytology or histology).


RESULTS
Among 21,747 Pap smears, 372 were discordant around the test threshold, requiring verification. In the primary analysis PAPNET detected four more true positives than conventional reading; difference in sensitivity 1.29% (95%CI -5.79 to 8.36%, P=.40). There were two extra false positives using PAPNET; difference in the false positive rate 0.0097% (95%CI -0.122 to 0.142%, P=.47). The results of the combined cytology and histology analysis were similar; difference in true positive rate 0.29% (95%CI -6.76 to 7.34%, P=.50) and difference in false positive rate 0.024% (95%CI -0.098 to 0.15%, P=.39).


CONCLUSIONS
This is an efficient and valid study design where the objective is to examine the comparative accuracy of two tests. The design provides an efficient means of estimating the difference between true positive and false positive detection by the two tests, which often is sufficient information for policy decisions.
Irwig
Les
L
Screening and Test Evaluation Program, School of Public Health, University of Sydney, Edward Ford Building A27, NSW 2006, Sydney, Australia. lesi@health.usyd.edu.au
Macaskill
Petra
P
Farnsworth
Annabelle
A
Wright
R Gordon
RG
McCool
Jan
J
Barratt
Alexandra
A
Simpson
Judy M
JM
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D065006:Papanicolaou Test; D011237:Predictive Value of Tests; D012015:Reference Standards; D018401:Sample Size; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014626:Vaginal Smears / Q000379:methods*