A greater percentage of satisfactory Pap tests were obtained when using LBCC (84.0%) compared with the CPT (60.5%), P ".001 (Figure 1). Also, significantly fewer unsatisfactory and SBLB Pap tests were reported using LBCC (1.2% and 14.8%) compared with the CPT (3.8% and 35.7%). For the colposcopy group, significantly more satisfactory Pap tests were reported for LBCC compared with the CPT (81.7% and 55.3%, respectively; P <.001). Similar results were also noted for the screening group. These significant results were maintained when the data were adjusted for the 3 age groups (Table 1).
The frequencies of cytologic diagnoses for LBCC and the CPT are seen in Table 2. The LBCC method detected a significantly greater percentage of women with low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Pap tests results (7.4% and 3.7%, respectively) compared with the CPT (1.7% and 1.7%, respectively). Similar significant results were noted when the LBCC and CPT groups were stratified into the screening and colposcopy populations. When both groups were adjusted for age, a greater percentage of LSIL and HSIL diagnoses were noted for LBCC in all 3 age ranges compared with the CPT (Table 4). The classification of atypical squamous cells of undetermined significance (ASCUS) cases was not modified by LBCC compared with the CPT. Because of the limited number of squamous cell carcinoma diagnoses reported, a comparison between the 2 groups was not possible.
The frequency of histologic diagnoses in the 2 groups closely paralleled Pap test diagnoses in the same populations. The LBCC and CPT groups had 5.4% and 1.0% cervical intraepithelial neoplasia 1 (CIN 1) histologic diagnoses, respectively, while 5.9% and 1.7% of the women had histologic diagnoses of CIN 2 and 3, respectively. These results were also maintained consistently across all 3 age ranges. The predictive value of a positive LBCC test (93.9%) was similar to that for the predictive value of a positive CPT (87.8%) when based on available histology results (Table 5). The sensitivity and specificity were equivalent for each test. Of all women with an LSIL or more severe Pap test result in each group, 1.9% of women in the CPT group and 6.5% of women in the LBCC group had cervical biopsies indicating CIN 1 or more severe disease.
Discussion
Pap test specimen adequacy results reflect whether the most likely site for neoplasia of the cervix—the transformation zone—has been sampled properly. LBCC provided significantly greater rates of satisfactory specimen adequacy than the CPT. Also, compared with the CPT, LBCC effectively reduced the number of SBLB and unsatisfactory specimen adequacy reports. Our findings are consistent with those of studies published previously that used split sample collection techniques.6,7 The improvement of Pap test adequacy using LBCC may be because a clearer inspection of pertinent normal and abnormal cells is achieved by eliminating or minimizing obscuring inflammatory cells, red blood cells, other debris, and clumped or overlapped cells.13 A significant decrease in unsatisfactory Pap tests reduces the extra cost, time, and patient and clinician inconvenience incurred from the necessity of repeating a nonrepresentative Pap test. These advantages may be of particular importance to patients, clinicians, and third-party payers.
Also, in regard to specimen adequacy, LBCC performed better than the CPT for women of all age ranges. This is especially important for older women who typically have a greater frequency of unsatisfactory Pap tests because their active transformation zones are positioned deeply within the endocervical canal and are often inaccessible to comprehensive sampling. In addition, a thin atrophic epithelium (commonly seen in the older age group) is more easily traumatized during sampling, which causes potentially obscuring bleeding. Yet, LBCC reduced the rate of unsatisfactory Pap tests by approximately 50% for women older than 40 years. Other than the advantage of filtering unwanted cells, the difference may be explained by the fact that 80% of cervical cells are discarded with the collection devices and not transferred to a glass slide using the CPT method.3 In contrast, nearly all cells are transferred to solution with LBCC. Thus, the larger specimen obtained with the sampling method used in LBCC increases the availability of a typically limited number of endocervical cells retrieved from post-treatment and postmenopausal women who are routinely more difficult to sample.
The ability of the Pap test to detect cytologic changes consistent with neoplasia, when present, is critically important. In our trial, the LBCC method detected a greater percentage of women with LSIL and HSIL compared with the CPT. Approximately 4 times the number of women with LSIL and twice the number of cases of HSIL were detected by LBCC compared with the CPT. These results replicate or surpass those found in studies that evaluated LBCC using a split sample method.6-9 Twice the rate of neoplasia detection by LBCC has been reported in studies using the split sample method. Our results, based on a direct-to-vial study design, may portray the true potential for LBCC to detect cervical neoplasia. A cleaner monolayer Pap test with a more comprehensive cellular specimen likely accounts for these remarkable differences. Similarly, the reduced number of unsatisfactory and SBLB Pap tests using LBCC may contribute to the greater yield of SILs. Of note, LBCC did not detect a significantly greater rate of ASCUS Pap test results; this may create problematic management decisions for some clinicians.14 The ability of LBCC to detect a greater percentage of women with SILs was maintained for the general screening population, the colposcopy cohort, and across the 3 age ranges. LBCC may be better able to detect women with HSIL, a lesion unlikely to resolve spontaneously. Women with HSIL (Figures 2A and B) and a comparable histologic diagnosis deserve prompt therapy for this true cancer precursor. Although many women with LSIL have disease that may regress to normal, as many as 20% to 40% of these women will have histologically confirmed CIN 2 or 3 that deserves treatment as well.15