Methods
Subjects
In our clinical study one group of women was enrolled prospectively, and a second group was considered retrospectively. The first group (LBCC) consisted of 1004 nonpregnant women aged 18 years or older with an intact cervix. The second group consisted of 2110 women with a similar patient profile who had a CPT collected at the same clinics during the 2 years immediately preceding the initiation of the trial.
To ensure an enriched sample of women with cervical neoplasia, approximately 20% of the subjects in both cohorts were included from women presenting consecutively for a colposcopy examination following an abnormal CPT result. The remaining 80% of the subjects represented a general screening population of women presenting for a routine Pap test. All subjects were seen at 1 of 3 clinics: the Family Medicine Center, the Obstetrics and Gynecology Clinic, or the Comprehensive Cancer Center at the Medical College of Georgia in Augusta.
Equipment and Materials
Samples for CPTs and LBCC (ThinPrep Pap Test, Cytyc Corporation, Boxborough, Mass) were collected using a plastic Ayre spatula and cytobrush (Medscand, North Hollywood, Fla). Cervical cells from the second group were processed by CPT methods. Cervical cells from the prospectively enrolled group were preserved and transferred in LBCC solution (PreservCyt, Cytyc Corporation). Cervical samples for the LBCC test were processed using the ThinPrep 2000 Processor (Cytyc Corporation).12
Study Design
Eligible prospectively enrolled women presenting consecutively for a routine Pap test or colposcopy examination at any of the 3 designated clinics signed an internal review board-approved informed consent form before participating. After properly visualizing the cervix, a plastic Ayre spatula was used to collect an ectocervical sample. Another sample was collected using a cytobrush rotated 90° to 180° within the endocervical canal. The spatula and cytobrush were then immediately rinsed vigorously in the LBCC solution. The container was sealed, labeled, and sent to the cytology laboratory for processing according to the manufacturer’s instructions.12 Cytotechnicians or pathologists in the Department of Pathology, Medical College of Georgia (MCG), evaluated all cytology and histology specimens. Cervical cytology was reported using the Bethesda System.
Computerized records from the MCG Cytology Laboratory were used to establish the second group. CPT records with similar patient profiles and clinic affiliation were selected chronologically beginning the day before the initiation of the trial and working backward in time until 2110 records were obtained (approximately 2 years). Cervical specimens were collected previously from this group using the same types of collection devices and technique as that for the LBCC group. However, immediately following sample collection these endocervical and ectocervical cells were plated on a glass slide, fixed, and sent to the cytology laboratory for Pap staining and diagnosis.
Statistical Analysis
The proportion of subjects in each of the Pap test adequacy groups (satisfactory, unsatisfactory, and satisfactory but limited by [SBLB]) were compared between the sample and control groups for the total study group, the colposcopy and general screening cohorts, and the 3 age groups (18-30 years, 31-40 years, 41 years or older). The chi-square statistic was used to compare the proportions unless the tables included cells with expected counts less than 5; for those cases we used the Fisher exact test as extended to tables larger than 2×2. A summary comparison controlling for age group was made using the Cohran-Mantel-Haenszel chi-square statistic. Average age was compared between the groups using the Student t test. At the given sample size the power was calculated to be 80% or greater for detecting a difference in positive rates of 3.5% between the LBCC and the CPT.
Results
Subjects in both groups were comparable by type of clinical visit. Consequently, 1004 LBCC subjects and 2110 CPT subjects were included in the data analysis. The routine Pap test screening group consisted of 796 and 1585 subjects in the LBCC and CPT groups, respectively, representing 79.0% of each population. Approximately 21.0% of the LBCC and CPT subjects (208 and 425, respectively) were represented by women presenting for colposcopy examination following an abnormal Pap test result. Subjects were also stratified into 1 of 3 age ranges for analytic purposes. Thus, 423 and 602 subjects were aged between 18 and 30 years; 287 and 523 subjects were aged 31 to 40 years; and 294 and 885 subjects were aged 41 years or older for the LBCC and CPT populations, respectively. A statistically significant difference between the age distributions was noted (P <.001) with a greater proportion of younger subjects in the LBCC group (mean age=35.0 years) than in the CPT cohort (mean age=39.8 years).