Loop electrosurgical excision procedure (LEEP) has become a widely accepted and standard procedure for treating preinvasive cervical lesions and diagnosing invasion.1–3 Both LEEP and cold knife cone biopsy are effective as diagnostic and therapeutic modalities for low-grade and preinvasive (high-grade) lesions of the cervix. Cold knife cone biopsy is required for some women and has been the standard by which other methods have been compared. However, LEEP is currently being used for almost all lesions that formerly required a cold knife cone biopsy. There is evidence that LEEP is as effective as cold knife cone biopsy in treating cervical dysplasia and has the advantages of being done in an outpatient setting with local anesthesia, few perioperative complications, and low cost.3–10
It is particularly important for all patients who have either a cold knife cone biopsy or a LEEP to have adequate follow-up subsequent to their procedures. Studies on progression of cervical dysplasia indicate that, after ablative or excision treatment for squamous intraepithelial lesion, the risk of progression to invasive disease is five times higher than in the general population (Lund ED, Robinson WR, Adams J, O'Quinn AG. The predictive value of LEEP specimen margin status for residual/recurrent cervical intraepithelial neoplasia [abstract]. Gynecol Oncol 1997;64:307).9,11,12 Thus, noncompliance with recommended follow-up poses a significant risk to the patient in that persistent, recurrent, or progressive disease may not get treated. However, there is limited data on posttreatment patient compliance with follow-up recommendations and time to follow-up as it relates to type of excision procedure performed. To address this issue, our study examined compliance with follow-up recommendations in a group of low-income women undergoing LEEP in our clinic or cold knife cone biopsy in the hospital operating room for cervical dysplasia. In addition, we sought to identify and describe demographic variables that may be predictive of compliance after LEEP or cold knife cone biopsy.
MATERIALS AND METHODS
After receiving approval from the Institutional Review Board of Maricopa Medical Center, a retrospective longitudinal cohort study of 187 patients from the Women's Care Clinic at Maricopa Integrated Health System, who underwent a LEEP or a cold knife cone biopsy from January 2001 through January 2003, was performed. Incarcerated patients were excluded from the study.
Data were collected on age, race, payor source, gravidity, parity, primary language, type and date of procedure, cytology, colposcopy biopsy, excision specimen pathology, and indication for LEEP compared with cold knife cone biopsy. We also included the recommendations given to each patient and indication of whether these recommendations were provided by a physician or nonphysician. The length of time between procedure and follow-up was also recorded. The data sources included the patient's medical records, surgical logs, pathology reports, and colposcopy logs.
Patients were defined as noncompliant if there was no documentation of compliance with recommended follow-up within the first posttreatment year. The recommendations for follow-up after treatment included repeat Pap test, colposcopy, or treatment for recurrent or persistent cervical dysplasia or cancer or a combination of these.
A power analysis was performed before data collection to determine the approximate sample sizes needed to detect a difference between the groups. Assuming compliance in the cold knife cone biopsy group of 50% and compliance in the LEEP group of 20%, to achieve a power of 80% with alpha at 0.05, using a two-tailed test, 48 patients were required in each group. Univariable analyses were performed by using t tests and χ2 tests as appropriate. Variables significant in the univariable analyses were included in the multivariable analysis. Multivariable analysis was performed by using logistic regression. Because the outcome of interest, compliance with follow-up, was not rare (greater than 10% incidence), the odds ratios and confidence intervals from logistic regression were adjusted according to the method described by Zhang and Yu.13 This method corrects for falsely inflated odds ratios yielded from logistic regression with a nonrare outcome. For all analyses, P≤.05 was considered significant.
Loop electrosurgical excision procedure was performed on 107 patients, and 80 patients had a cold knife cone biopsy. Fifty-two patients were excluded because they were incarcerated. Thus, there were 135 included patients, with 81 LEEPs (60%) and 54 cold knife cone biopsies (40%). Patient ages ranged from 16 to 80 years, with the mean of 34 (standard deviation 12) years. The majority (57%) of patients were Hispanic, and most were multiparous (79%). Primary languages were evenly distributed between English and Spanish. (Table 1).
The majority of patients (87%) presented for their postoperative appointments (2 weeks after the procedure), but just over half (55.6%) were compliant with the recommended follow-up within 1 year. Patients who did not follow up for their postoperative visits were considered 100% noncompliant. None of those who failed their postoperative appointment returned within the year. Our analysis on compliance included the 13% (14 LEEP and 4 cold knife cone biopsy patients) of patients who did not present for their postoperative visits.
The type of procedure was significant in predicting compliance; 74.1% of cold knife cone biopsy patients were compliant compared with 43.2% of LEEP patients (relative risk [RR] 1.64, 95% confidence interval [CI] 1.30–1.87). Subjects older than the median age of 33 were more compliant (63.8%) than younger subjects (47.0%) (RR 1.41, 95% CI 0.99–1.78) (Table 2). When compared by a t test, the mean age between noncompliant (mean 31) and compliant (mean 37) patients was significant (P=.003). Also, of all those who did not follow up for their 2-week postprocedure visit, only one patient was more than 40 years old. The other variables (race, payor source, gravidity, parity, primary language, and indication for procedure) were not significant predictors of compliance. The preoperative indication for the procedure, whether high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, positive endocervical curettage, discrepancy between Pap test and colposcopic biopsy, or inadequate/unsatisfactory colposcopy, was not a predictor of compliance, and no significant differences in these diagnoses between the LEEP and cold knife cone biopsy groups were noted (66.3% of LEEPs and 79.2% of cold knife cone biopsies were done for high-grade disease, P=.104).
Because only procedure type and age were significant predictors of compliance in the univariable analysis, only these variables were included in the multivariable analysis. In multivariable analysis, procedure type was a significant predictor of compliance, with cold knife cone biopsy patients being more compliant (RR 1.60, 95% CI 1.22–1.86), but age was not a significant predictor. When an interaction between age and type of procedure was tested in the regression model and via a Breslow Day test14 for homogeneity of the odds ratio, there was a trend (P=.07) toward type of procedure having a more important effect on compliance in younger patients than in older patients (Fig. 1).
There is evidence that supports the use of LEEP for all indications previously reserved for cold knife cone biopsy in the evaluation and treatment of cervical preinvasive, and even microinvasive, disease. Both procedures have similar rates of recurrence.4,7,8,10,15 The overall efficacy of LEEP in treating cervical dysplasia has been reported to be greater than 90% and ranging from 67% to 97% in published studies (Lund et al, abstract).1,2,5,6,9–11,16–20 Loop electrosurgical excision procedure has become a much more effective alternative to cold knife cone biopsy because of less hemorrhaging, less anesthetic morbidity, less cervical stenosis, ease, less time involved in an outpatient setting, and decreased cost.7,8,10,21
Recurrence rates after LEEP vary according to the study, length of follow-up, and type of surveillance used to detect recurrences. Overall recurrences have been reported between 4% and 40%. Gonzalez et al11 found that both women with positive and those with negative margins had significant rates of recurrence: 46% and 26%, respectively. Therefore, the importance of long-term follow-up should be emphasized to all patients undergoing this procedure. However, in a randomized study of cold knife cone biopsy compared with LEEP, Duggan et al4 noted a greater number of women lost to follow-up after LEEP compared with cold knife cone biopsy (10 versus 3 women, respectively).
Our findings show a significant difference in compliance, with follow-up recommendations within a year, after LEEP compared with cold knife cone biopsy. Women undergoing LEEP had about half the compliance of those who underwent cold knife cone biopsy. When compared by means of a t test, the only other predictive factor was less compliance in the younger women in the LEEP group. When an interaction between age and procedure type was explored, there was some indication that the difference in noncompliance was more marked in younger patients. A number of the variables examined did not have any association with compliance, such as payor source, who gave the postprocedure instructions, diagnosis, and indication for procedure, including severity of dysplasia.
One can only speculate from other studies on compliance as to the reasons for noncompliance in our studied population. It has been suggested that the lower compliance in the LEEP group may be due to the fact that cold knife cone biopsy is done in the hospital setting, usually under general anesthesia. Loop electrosurgical excision procedure, being viewed as a simpler procedure than cold knife cone biopsy, may give the patient the unspoken impression that their diagnosis is not as severe and, therefore, has less need for follow-up. It is likely this perception plays a role, but compliance also involves other psychosocial issues that must be addressed.
Studies have assessed barriers to screening for cervical cancer and psychological and sociocultural perspectives on follow-up of an abnormal Pap test. It has been estimated that 20–70% of women who have a screening Pap test and are diagnosed with a preinvasive lesion do not follow up.22–24 Default rates to colposcopy clinics have been reported as high as 63%.25,26
In examining minority urban women, Behbakht et al27 reported that fatalistic attitudes, lack of family support, and lack of information and patient education about the risk of cervical cancer has a significant association with lack of Pap screening. Breitkopf et al28 showed adequate communication with the provider was important in patient compliance. In addition, 25% of Hispanic women stated it would be difficult or not easy to follow up, and fewer than 25% of women in the study would call the clinic or come in requesting results.28 Conclusions from the study by Breitkopf et al28 suggested that education, assisting patients in anticipating obstacles, family support, addressing a partner's negative reaction, more effective communication, and assigning a greater importance to recommended follow-up may improve compliance. Because our study population was similar to the patients studied by Breitkopf and Behbakht, the same issues, misconceptions, beliefs, and obstacles likely affect compliance in our patients.
Our results are similar to those of studies examining compliance with Pap test screening and follow-up of abnormal Pap tests in urban, minority populations. Many of the same issues examined in the Pap screening compliance studies are likely the source of poor follow-up after excision procedures and, in particular, after LEEP. In an outpatient setting, it is even more imperative to make sure that all aspects are addressed to ensure high compliance with follow-up. In addition, it must be made clear what is the follow-up evaluation. Studies have shown that human papillomavirus (HPV) testing at 6 months post-LEEP has the best predictive value for persistent or recurrent disease and is the least invasive test.29 Using HPV testing as a posttreatment evaluation may allow women to be better prepared, less anxious about the follow-up visit, and therefore, more likely to be compliant. A recent randomized study found improved compliance in patients presenting to a colposcopy clinic if patients were called in advance of their appointments.30 This is another relatively simple intervention that may improve compliance in our LEEP patients.
We need to work with our associates in the clinic and office to make sure that time is available for education and to address all the issues mentioned so that compliance with follow-up is achieved. Studies are needed to determine what interventions, particularly in younger populations, might improve compliance in patients undergoing a LEEP. Compliance should be a high priority, especially for the more commonly used in-office LEEP procedure. It is through these continued efforts to improve compliance that we can achieve more effective screening and better follow-up so that at-risk populations are evaluated and treated for recurrent or persistent disease.
Our study is limited by the biases inherent in its retrospective design. In addition, evaluation was from one clinic of a county hospital with a population consisting mostly of multiparous Hispanic women with a high rate of no insurance and Medicare patients. As a result, some caution is warranted before generalizing our findings to other patient populations.
1. Prendiville W, Cullimore J, Norman S. Large loop excision of the transformation zone (LLETZ). A new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynaecol 1989;96:1054–60.
2. Whiteley PF, Olah KS. Treatment of cervical intraepithelial neoplasia: experience with the low-voltage diathermy loop. Am J Obstet Gynecol 1990;162:1272–7.
3. Mor-Yosef S, Lopes A, Pearson S, Monaghan JM. Loop diathermy cone biopsy. Obstet Gynecol 1990;75:884–6.
4. Duggan BD, Felix JC, Muderspach LI, Gebhardt JA, Groshen S, Morrow CP, et al. Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. Am J Obstet Gynecol 1999;180:276–82.
5. Spitzer M, Chernys AE, Seltzer VL. The use of large-loop excision of the transformation zone in an inner-city population. Obstet Gynecol 1993;82:731–5.
6. Gold M, Dunton CJ, Murray J, Macones G, Hanau C, Carlson JA Jr. Loop electrocautery excisional procedure: therapeutic effectiveness as an ablation and a conization equivalent. Gynecol Oncol 1996;61:241–4.
7. Mathevet P, Dargent D, Roy M, Beau G. A randomized prospective study comparing three techniques of conization: cold knife, laser, and LEEP. Gynecol Oncol 1994;54:175–9.
8. Girardi F, Heydarfadai M, Koroschetz F, Pickel H, Winter R. Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial. Gynecol Oncol 1994;55:368–70.
9. Wright TC, Gagnon S, Richart RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol 1992;79:173–8.
10. Oyesanya OA, Amerasinghe C, Manning EA. A comparison between loop diathermy conization and cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy. Gynecol Oncol 1993;50:84–8.
11. Gonzalez DI Jr, Zahn CM, Retzloff MG, Moore WF, Kost ER, Snyder RR. Recurrence of dysplasia after loop electrosurgical excision procedures with long-term follow-up. Am J Obstet Gynecol 2001;184:315–21.
12. Murdoch JB, Grimshaw RN, Monaghan JM. Loop diathermy excision of the abnormal zone. Int J Gynecol Cancer 1991;1:105–111.
13. Zhang J, Yu KF. What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 1998;280:1690–1.
14. Breslow NE, Day NE. Statistical methods in cancer research. Volume I - The analysis of case-control studies. IARC Sci Publ 1980;5–338.
15. Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol 1994;84:996–1000.
16. Hanau CA, Bibbo M. The case for cytologic follow-up after LEEP. Acta Cytol 1997;41:731–6.
17. Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol 1992;99:990–3.
18. Keijser KG, Kenemans P, van der Zanden PH, Schijf CP, Vooijs GP, Rolland R. Diathermy loop excision in the management of cervical intraepithelial neoplasia: diagnosis and treatment in one procedure. Am J Obstet Gynecol 1992;166:1281–7.
19. Bigrigg A, Haffenden DK, Sheehan AL, Codling BW, Read MD. Efficacy and safety of large-loop excision of the transformation zone. Lancet 1994;343:32–4.
20. Shafi MI, Dunn JA, Buxton EJ, Finn CB, Jordan JA, Luesley DM. Abnormal cervical cytology following large loop excision of the transformation zone: a case controlled study. Br J Obstet Gynaecol 1993;100:145–8.
21. Naumann RW, Bell MC, Alvarez RD, Edwards RP, Partridge EE, Helm CW, et al. LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol 1994;55:224–8.
22. Laedtke TW, Dignan M. Compliance with therapy for cervical dysplasia among women of low socioeconomic status. South Med J 1992;85:5–8.
23. McKee D. Improving the follow-up of patients with abnormal Papanicolaou smear results. Arch Fam Med 1997;6:574–7.
24. Paskett ED, White E, Carter WB, Chu J. Improving follow-up after an abnormal Pap smear: a randomized controlled trial. Prev Med 1990;19:630–41.
25. Brooks SE, Gordon NJ, Keller SJ, Thomas SK, Chen TT, Moses G. Association of knowledge, anxiety, and fear with adherence to follow up for colposcopy. J Low Genit Tract Dis 2002;6:17–22.
26. Yauger BJ, Rodriguez M, Parker MF. Default from colposcopy and loop excision electrocautery procedure appointments in a military clinic. J Low Genit Tract Dis 2005;9:78–81.
27. Behbakht K, Lynch A, Teal S, Degeest K, Massad S. Social and cultural barriers to Papanicolaou test screening in an urban population. Obstet Gynecol 2004;104:1355–61.
28. Breitkopf CR, Catero J, Jaccard J, Berenson AB. Psychological and sociocultural perspectives on follow-up of abnormal Papanicolaou results. Obstet Gynecol 2004;104:1347–54.
29. Wright TC Jr, Cox JT, Massad LS, Carlson J, Twiggs LB, Wilkinson EJ. 2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia. Am J Obstet Gynecol 2003;189:295–304.
30. Oladipo A, Ogden S, Pugh S. Preclinic appointment telephone contact: an effective intervention for colposcopy clinic nonattendance. J Low Genit Tract Dis 2007;11:35–8.