The Efficacy of Liquid-Based Cervical Cytology Using Direct-to-Vial Sample Collection

,

Original Research

The Efficacy of Liquid-Based Cervical Cytology Using Direct-to-Vial Sample Collection

J Fam Pract. 2000 November;49(11):1005-1011

By

Daron G. Ferris, MD

References

1. Agency for Health Care Policy and Research. Evidence report/technology assessment no. 5: evaluation of cervical cytology. Rockville, Md: Agency for Health Care Policy and Research; 1999. US Department of Health and Human Services AHCPR publication no. 99-E010.

2. Lee KR, Ashfaq R, Birdsong GG, Corkill ME, McIntosh KM, Inhorn SL. Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening. Obstet Gynecol 1997;90:278-84.

3. Hutchinson ML, Agarwal P, Denault T, Berger B, Cibas ES. A new look at cervical cytology: ThinPrep multicenter trial results. Acta Cytol 1992;36:499-504.

4. Ferris DG, Wright TC, Jr, Litaker MS, et al. Comparison of two tests for detecting carcinogenic HPV in women with Papanicolaou smear reports of ASCUS and LSIL. J Fam Pract 1998;46:136-41.

5. Ferenczy A, Franco E, Arseneau J, Wright TC, Richart RM. Diagnostic performance of hybrid capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study. Am J Obstet Gynecol 1996;175:651-56.

6. Roberts JM, Gurley AM, Thurloe JK, Bowditch R, Laverty CRA. Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear. Med J Aust 1997;167:466-69.

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8. Corkhill M, Knapp D, Hutchinson ML. Improved accuracy for cervical cytology with the ThinPrep method and the endocervical brush-spatula collection procedure. J Lower Genital Tract Dis 1998;2:12-16.

9. KR, Ashfaq R, Birdsong GG, Corkhill ME, McIntosh KM, Inhorn SL. Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening. Obstet Gynecol 1997;90:278-84.

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BACKGROUND: Previous studies of liquid-based cervical cytology (LBCC) have used a split sample collection technique that creates a potential negative bias for its evaluation. Thus, the full diagnostic potential of LBCC has not been established. The purpose of our study was to determine rates of specimen adequacy and cervical cytologic and histologically confirmed diagnoses obtained with a liquid-based Papanicolaou (Pap) test using a direct-to-vial sample collection technique and compare these results with those obtained using the conventional Pap test (CPT).

METHODS: A total of 1004 nonpregnant women aged 18 years or older with an intact cervix had Pap tests collected with an Ayre spatula and cytobrush, and the sample was placed in a preservative solution. The specimens were processed as thin layer Pap tests according to the manufacturer’s specifications. Another group of 2110 women with a similar patient profile had a CPT collected immediately preceding the initiation of the trial. The subjects in each group consisted of an equal percentage of women presenting for a routine Pap test or a colposcopy examination. We compared the distributions of diagnostic categories between the groups using a chi-square test.

RESULTS: A significantly greater percentage of satisfactory Pap tests were obtained using LBCC (84.0%) compared with the CPT (60.5%, P <.001). Fewer satisfactory but limited by (SBLB, 14.8%) and unsatisfactory (1.2%) Pap tests were reported using LBCC compared with the CPT (35.7% and 3.8%, respectively, c2=170.7, P <.001). A significantly greater percentage of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Pap test results were reported using LBCC (7.4% and 3.7%, respectively) compared with the CPT (1.7% and 1.7%, respectively, c2=74.4, P & .001). The predictive value of a positive LBCC test (93.9%) was similar to that for a positive CPT (87.8%) when compared with histology results.

CONCLUSIONS: Compared with the CPT, LBCC detected a significantly greater percentage of satisfactory Pap tests and significantly reduced the number of unsatisfactory and SBLB tests. Four times the percentage of LSIL and twice the percentage of HSIL Pap test results were obtained using LBCC compared with the CPT. These findings demonstrate that LBCC significantly improves the adequacy of Pap tests and may increase the rate of detection of cervical neoplasia compared with the CPT.

The Papanicolaou (Pap) test is one of the most common and effective cancer screening tests used by primary care clinicians. However, a recent study conducted through the Agency for Health Care Policy and Research¹ estimated that the true sensitivity of the Pap test is only 51%. Two thirds of the false-negative results occur because of sampling error. The first liquid-based cervical cytology (LBCC) test was approved for clinical use by the United States Food and Drug Administration in 1996.² With LBCC, standard cervical cytology sampling devices are used to obtain a sample from the cervix. The sampling devices are then rinsed in a buffered alcohol transport and preservative solution instead of immediately transferring the cells to a glass slide. Sampling error is reduced, since all the cells are transferred into solution, in contrast with the conventional Pap test (CPT), in which only 20% of the cells are actually transferred to the glass slide.³ The cytologic specimen in solution is then sent to the laboratory where most of the debris, leukocytes, and erythrocytes are filtered from the specimen and a thin layer Pap test is prepared using a special processor. The cells are dispersed evenly with relatively little clumping or overlapping or obscuring debris (Figures 1A and B). The resulting clean smear is circular and contains approximately half the number of representative cells of a CPT. Residual cervical cells in solution that are not initially used for the Pap test may be tested at a later date for lower genital tract pathogens, such as carcinogenic human papillomavirus.^4,5

Liquid-based thin layer cervical cytology has performed favorably in studies using split sample collection techniques.^6-9 With the split sample technique, the cytologic specimen is first transferred to a glass slide for the CPT before transferring the remaining cervical cells to the liquid transport fluid. Evaluation of the LBCC Pap test using this nonrandom study design may be biased, since it is based solely on cells normally discarded. The CPT slides receive the first and perhaps better cellular sample; thus, the quality of that specimen may be vastly different than that available for LBCC. Currently, there are minimal data available in which LBCC was evaluated as it was intended to be used, for a primary cytologic specimen.^10,11 Thus, the full diagnostic potential of this new Pap test technique has not been fully realized. The purpose of our trial was to determine the rates of specimen adequacy and cervical cytologic and histologically confirmed diagnoses obtained with LBCC using a direct-to-vial collection technique and compare these results with those obtained using the CPT.