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ORIGINAL RESEARCH |
From the 1Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University and Sparrow Hospital, Lansing, Michigan; and 2Department of Epidemiology, Michigan State University, East Lansing, Michigan.
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ABSTRACT |
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METHODS: Two hundred women each had 2 simultaneous Pap test collections. One specimen was randomly contaminated with 0.5 mL of water-based lubricant after collection. The physician was blinded as to which collection was contaminated. Both specimens were sent for cytology. Cytopathologists were blinded to the study. The rate of abnormal cytology and discordance between the control and the contaminated specimens was estimated. The discordance of secondary diagnoses, such as yeast infections and bacterial vaginosis, was also estimated.
RESULTS: The incidence of abnormal cytology was similar in the contaminated specimens and the control specimens (6.5%, 95% confidence interval [CI] 3.5–10.9% versus 7.0%, 95% CI 3.9–11.5%). The rate of disagreement between the 2 specimens collected from each patient was 7.5% (95% CI 4.6–12.1%) and is similar to previously published estimates of discordance using conventional cytology. Secondary diagnoses, such as yeast infections or bacterial vaginosis, were similar in both groups, suggesting no interference from the lubricant.
CONCLUSION: Water-based lubricant does not affect liquid-based cervical cytology Pap testing. Water-based lubricant does not affect secondary diagnoses such as bacterial vaginosis or yeast infections.
LEVEL OF EVIDENCE: II-1
In a study of adolescents, the fear of pain with the pelvic examination was listed as the most common reason for not presenting for Pap testing or follow-up.3 Although not yet clinically tested, one potential method for reducing discomfort during the examination for all women is coating the speculum with a water-based lubricant. Reducing discomfort during the examination may increase the likelihood of at-risk patients returning for follow-up.
Current gynecology texts either discourage the use of any lubricant other than tap water or do not discuss the issue. These authors state concern over possible artifacts confounding cytological interpretation as reasoning against the use of lubricant. Only one general practice book advocated the use of lubricant on the speculum during Pap test collection.16 Two studies were published showing no difference in conventional Pap test adequacy or the rate of abnormal Pap tests between patients who had lubricant used and those who did not.17,18 Neither of these studies compared the rate of discordance between a lubricated Pap test and a nonlubricated Pap test in the same patient.
To evaluate the effect of lubricant on liquid-based cytology, we present a randomized, blinded study of whether lubricant affects the cervical cytology, the adequacy of the specimen, and the secondary diagnoses such as bacterial vaginosis or yeast infection in adult women.
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MATERIALS AND METHODS |
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The cytology results were then unblinded and evaluated for correlation of the cytopathology, the number of "unsatisfactory" samples, and any secondary diagnoses. Power analysis was conducted at this time. Because this was an equivalence study, a power of 80% was set to determine the ability of the study to detect a significant difference. The results from each group were compared using the rate of disagreement between the 2 samples and compared with previously published estimates. The differences and their P values between the secondary diagnoses were evaluated using the McNemar test of marginal dissimilar results. The public domain software R (http://www.r-project.org) and Microsoft Excel were used for all statistical analyses. This study was reviewed and approved by the institutional review board of Michigan State University (IRB #03–776) and the board’s decision accepted by Sparrow Hospital (IRB #3041).
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RESULTS |
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Internal review of the discordant specimens by a third cytotechnologist and a cytopathologist changed the diagnosis of 3 of the 30 slides. First, a contaminated specimen that was initially negative was changed to ASC-US, matching the control specimen. Second, a contaminated specimen that was initially negative was changed to ASC-US, and the control specimen was confirmed as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H). Third, a control specimen that was initially negative was changed to LSIL, matching the contaminated specimen. Because most Pap tests are not screened twice and this deviated from the standard practice, these changes were not included in the analysis of the results.
When comparing the contaminated samples to the control samples, there was a similar incidence of abnormal cytology (6.5%, 95% CI 3.5–10.9% versus 7.0%, 95% CI 3.9–11.5%). Our laboratory (Sparrow Regional Laboratory) reports an overall 4.40% abnormal cytology rate with a 99.36% adequacy rate, consistent with our results. Our abnormal cytology rate may be slightly higher because of a higher risk patient population seen in the resident practice compared with private practice. There was no statistical difference in the number of specimens lacking endocervical cells, suggesting that lubricant does not interfere with the detection of these cells (Table 2)
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In addition to cervical cytology, we looked at secondary diagnoses and comments provided by the cytotechnologists to determine whether the contaminant affected the samples (Table 2). There was no statistically significant difference in the ability to diagnose bacterial vaginosis, yeast infection, or other pathology comments. The reported P values were determined by McNemar tests. The partially obscuring blood specimens in each group contained one specimen that was collected first and one specimen that was collected second, thus negating any possible bias from increased blood on the second collection due to trauma from the first spatula and cytobrush. The unnamed partially obscuring contamination was seen in the control specimen and was the second specimen collected, so lubricant was not the contaminant, but could have been blood from the trauma of the first collection.
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DISCUSSION |
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Two studies demonstrated that the use of water-based lubricant on the speculum did not affect the overall rate of inadequate conventional cytology.17,18 However, the studies did not address whether any direct contamination of the specimen with the water-based lubricant resulted in an unsatisfactory specimen. In addition, these studies were unblinded. Therefore, a potential bias in placing the speculum to minimize lubricant contamination was possible. Finally, the studies were done using conventional cytology, which is becoming obsolete.
In contrast, other reports have shown that certain brands of lubricant do affect the ability to interpret both conventional and liquid-based cervical cytology (Zardawi IM, Catterall N, Duncan J, Sullivan J, Warwick L. Effects of lubricant gel on conventional and liquid-based cervical smears [letter]. Acta Cytol 2003;47:704–5). Zardawi et al showed that the addition of certain unnamed brands of commercially available lubricant (2 of the 5 tested) resulted in a grainy appearance on the slide which could be misinterpreted as bacteria. They reported that this did not happen with the other 3 brands tested and did not happen using any of the 5 lubricants with a different commercial cytology solution. They suggested that the lubricants stuck to the Thinprep (Cytyc, Marlborough, MA) membrane used to collect the cells for slide preparation. Additionally, Cytyc, the manufacturer of Thinprep, discourages the use of lubricant and has sent out a letter to physicians discouraging the use of any lubricant during the collection process although they do not cite any supporting studies (letter sent to U.S. physicians from Cytyc Corporation, August 17, 2004).20
In contrast to these previous studies, our study was not designed to test whether lubricant on the speculum or in the solution would affect the rate of inadequacy, but rather whether directly contaminating the cells with lubricant before placing them in the PreservCyt solution would affect the cytological interpretation. This study also used each woman as her own control rather than attempting to match her with a cohort, allowing for direct comparison of cytological interpretation, thereby reducing the number of patients needed to show significance. In addition, our study attempted to eliminate technique bias by randomization after both specimens were collected.
Our results suggest that contamination of sampled cells by water-based lubricant does not affect the interpretation of liquid-based cervical cytology. We postulate that the water-based lubricant we used is completely miscible in the PreservCyt solution, thus rendering no significant influence on liquid-based cytology. In contrast, conventional Pap tests are immediately fixed to the slide at the time of collection, and lubricant may inhibit the ability of the fixative to prepare the cells for cytology.
Power analysis was conducted as part of the statistical analysis of the results. Using an estimated baseline prevalence of 6.4% discordance with our sample size of 200 patients, we had the ability to detect an increase of discordance up to 10%. Estimating the baseline discordance is difficult at best. As stated by Hessling et al, "In the comparison of results, new, imperfect preparations or tests are compared with old, imperfect preparations or tests."21 The baseline discordance was taken from a study published in 1975,19 where 2 Pap tests were taken from the same patient and sent to 2 different laboratories for diagnosis. Of the 2,823 paired slides, there was disagreement between the 2 labs in 177 slides that showed dysplasia (6.3%, 95% CI 5.4–7.3%). However, this study had unusually elevated and statistically significant differences in unsatisfactory smears at the 2 laboratories (151 unsatisfactory slides [5.3%, 95% CI 4.6–6.2%] versus 105 unsatisfactory slides [3.7%, 95% CI 3.1–4.5%]), which were not included in the analysis of discordance. Thus, the likely baseline discordance between 2 slides collected at the same time is higher than 6.4%. In contrast, our unsatisfactory rate (0.5%) is much smaller, and this was included in our discordance analysis.
In another study of simultaneously collected Pap tests by the same group of researchers, 17,737 patients had 2 specimens collected. In their analysis of the severe dysplasia and carcinoma in situ slides, there was agreement in only 2 of 51 patients, and in the mild-to-moderate dysplasia slides, there was agreement in only 29 of 211 patients. For example, in about one half of the women with a diagnosis of mild-to-moderate dysplasia on 1 slide, the other slide was read as normal. This demonstrates the huge variation that can occur between 2 simultaneously collected slides.
To further evaluate the accuracy and power of this study, we looked at the interobserver variability in cytology and histology. In one study of cervical cytology, the findings of general histopathologists and specialist cytopathologists reading 110 Pap tests was compared to determine the extent of agreement among them.22 The authors found that there was only moderate agreement among the specialists and poor agreement among general pathologists. In another study of cervical histology from colposcopy-directed biopsies, the interobserver agreement among the 2 specialist gynecopathologists, using only normal or dysplastic categories, was only 61%.23
In examining all of these data and the wide amount of variability, we determined that the power to detect an increase from a best-guess estimated discordance of 6.3% to 10% was sufficient. In addition to an acceptable rate of discordance, the rate of abnormal cytology was not significantly increased (6.5% versus 7.0%) in our study, but a much larger sample is required to show statistical equivalence when comparing the incidence of abnormal Pap tests as opposed to the rate of discordance between 2 simultaneously collected specimens.
We also looked at the possible interference of lubricant in the secondary diagnoses of bacterial vaginosis, yeast infections, or other comments provided by the cytotechnologists using conventional or liquid-based cytology. We found no statistical difference between the contaminated and control specimens.
Our study does have several limitations. First, we only included 200 women in our study. Although our power analysis showed an 80% chance of detecting a discordance of 10%, more samples would be better. Second, we only used Surgilube lubricant with the Thinprep system. We cannot extrapolate our results to other lubricants or other liquid-based cytology products. Third, we did not assess whether lubricant contamination affects other testing, possibly done at the same time as the Pap test, such as polymerase chain reaction testing for gonorrhea and chlamydia, wet mounts, cultures for group B streptococcus, mycoplasma, or ureaplasma or fetal fibronectin detection. Therefore, we do not recommend the use of lubricant during the initial obstetric physical examination, when these specimens are routinely collected, until further testing has been done.
In conclusion, liquid-based cytology is rapidly becoming the standard of care for Pap testing because of the increased sensitivity in detecting abnormal cervical cells. Adopting a new process for cytology warrants careful investigation into the method of specimen collection and the possible limitations and pitfalls. We have shown that Surgilube can be safely used with Thinprep cervical cytology without affecting the detection of abnormal cervical cells. Further studies are needed to determine whether cytology using other lubricants with Thinprep or other liquid-based cervical cytology systems are adversely affected. In addition, further studies are needed to show whether using water-based lubricant during pelvic exams actually results in less pain than using tap water. If the pain associated with Pap testing can safely be decreased, we owe it to our patients to institute these practices.
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Footnotes |
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No author has any association, financial or otherwise, with any company or product mentioned.
Presented at The American College of Obstetricians and Gynecologists District V Junior Fellow Annual District Meeting, Columbus, Ohio, September 17, 2004.
Corresponding author: Jon K. Hathaway, MD, PhD, 1322 East Michigan Avenue, Suite 220, Lansing, MI 48909; e-mail: Jon.Hathaway{at}byu.net.
doi:10.1097/01.AOG.0000192512.03576.da
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REFERENCES |
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2. American Cancer Society. Cancer facts and figures, 2004. Available at: http://www.cancer.org/downloads/STT/CAFF_finalPWSecured.pdf. Retrieved October 25, 2005.
3. Kahn JA, Chiou V, Allen JD, Goodman E, Perlman SE, Emans SJ. Beliefs about Papanicolaou smear and compliance with Papanicolaou smear follow-up in adolescents. Arch Pediatr Adolesc Med 1999;153:1046–54.
4. Kawada C. Gynecologic history, examination, and diagnostic procedures. In: DeCherney AH, Pernol ML, editors. Current obstetric and gynecologic diagnosis and treatment. 8th ed. East Norwalk (CT): Appleton & Lange; 1994. p. 613–32.
5. Stenchever MA. History, physical examination, and preventive health care. In: Stenchever MA, Droegemueller W, Herbst AL, Mishell DR Jr, editors. Comprehensive gynecology. 4th ed. St. Louis (MO): Mosby; 2001. p. 137–54.
6. Keye WR Jr. Gynecologic history, examination and diagnostic procedures. In: Scott JR, DiSaia PJ, Hammond CB, Spellacy WN, editors. Danforth’s obstetrics and gynecology. 7th ed. Philadelphia (PA): Lippincott-Raven; 1997. p. 604.
7. Cervical cytology screening. ACOG Practice Bulletin No. 45. American College of Obstetricians and Gynecologists. Obstet Gynecol 2003;102:417–27.[Medline]
8. Lichtman R, Papera S. Gynecology: well-woman care. Norwalk (CT): Appleton & Lange; 1990.
9. Rakel RE, editor. Textbook of family practice. 4th ed. Philadelphia (PA): Saunders; 1990.
10. Chestnutt MS, Dewar TN, Locksley RM. Office and bedside procedures. 1st ed. Norwalk (CT): Appleton & Lange; 1992.
11. Seidel HM, Ball JW, Dains JE, Benedict, GW, editors. Mosby’s guide to physical examination. 3rd ed. St. Louis (MO): Mosby; 1995.
12. Novak E, Hillard PA, Berek JS, editors. Novak’s gynecology. 13th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2002.
13. Curtis MG, Hopkins MP, editors. Glass’s office gynecology. 5th ed. Baltimore (MD): Williams & Wilkins; 1999.
14. Ryan KJ, Ryan KJ, Berkowitz RS, Barbieri RL, Dunaif AE, Kistner RW, editors. Kistner’s gynecology and women’s health. 7th ed. St. Louis (MO): Mosby; 1990.
15. Cunningham FG, Gant NF, Leveno KJ, Gilstrap, III, LC, Hauth JC, Wenstrom KD, editors. Williams obstetrics. 21st ed. New York (NY): McGraw-Hill; 2001. p. 227.
16. Pfenninger JL, Fowler GC. Procedures for primary care physicians. 1st ed. St. Louis (MO): Mosby; 1994.
17. Harer WB, Valenzuela G Jr, Lebo D. Lubrication of the vaginal introitus and speculum does not affect Papanicolaou smears. Obstet Gynecol 2002;100:887–8.
18. Amies AM, Miller L, Lee SK, Koutsky L. The effect of vaginal speculum lubrication on the rate of unsatisfactory cervical cytology diagnosis. Obstet Gynecol 2002;100:889–92.
19. Shulman JJ, Hontz A, Sedlis A, Walters AT, Balin H, LoScuito L. The Pap smear: take two. Am J Obstet Gynecol 1975;121:1024–8.[Medline]
20. Cytyc Corporation. Frequently asked questions—ThinPrep System. Available at http://www.cytyc.com/medical/medical_cervical_cancer_faq.shtml. Retrieved June 27, 2005.
21. Hessling JJ, Raso DS, Schiffer B, Callicott J Jr, Husain M, Taylor D. Effectiveness of thin-layer preparations vs. conventional Pap smears in a blinded, split-sample study: extended cytologic evaluation J Reprod Med 2001;46:880–6.[Medline]
22. O’Sullivan JP, Ismail SM, Barnes WSF, Deery ARS, Gradwell E, Harvey JA, et al. Interobserver variation in the diagnosis and grading of dyskaryosis in cervical smears: specialist cytopathologists compared with non-specialists. J Clin Pathol 1994;47:515–8.
23. Parker MF, Zahn CM, Vogel KM, Olsen CH, Miyazawa K, O’Connor DM. Discrepancy in the interpretation of cervical histology by gynecologic pathologists. Obstet Gynecol 2002;100:277–80.
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