Of the LEEP specimens, 47% (140 of 298) were noted to have the histologic risk factors for recurrent dysplasia of marginal (ectocervical and/or endocervical) or glandular involvement with dysplasia. When the rate of follow‐up abnormal cytology was stratified based on the presence of dysplasia at the histologic LEEP margin or endocervical glandular involvement with dysplasia, no statistical significance was found (P = .097) (Table 1). Ectocervical marginal status, endocervical marginal status, and glandular involvement were not independent risk factors for early cytologic abnormalities. However, the greater the cumulative number of risk factors identified in the LEEP specimen, the greater the risk for abnormal post‐LEEP cytology. This abnormal cytology rate increased from 24% when no risk factors were identified in the LEEP specimen to 67% when all three risk factors were present. This finding was statistically significant (P = .037) (Table 3).
A total of 254 (85%) patients in the study group had further follow‐up data that could be located beyond the initial 3‐month Papanicolaou smear. Subsequent dysplasia was found in 46 of 254 (18.1%) patients (Table 4). This recurrent dysplasia could represent residual or recurrent dysplasia because of the relatively short time of follow‐up. In those patients with normal post‐LEEP cytology, 8.0% had documented dysplasia on follow‐up with the mean time to diagnosis of approximately 8 months (range 2–12 months). Patients who had abnormal cytology on initial follow‐up cytology were found to have persistent or recurrent dysplasia 40.0% of the time (Table 4). The percentage of patients with recurrent dysplasia increased from 30% of patients diagnosed with ASCUS at initial follow‐up cytology to 82% of those with high‐grade squamous intraepithelial lesion on initial follow‐up cytology. The mean time to diagnosis was approximately 6.46 months (range 2–12 months). The rate of recurrence was significantly quicker among those patients with low‐grade squamous intraepithelial lesion and high‐grade squamous intraepithelial lesion on cytology (P < .001). There was no significant increased relative risk for the development of dysplasia among patients who had ASCUS or low‐grade squamous intra‐epithelial lesion cytology (P = .14). If, however, post‐LEEP cytology was high‐grade squamous intraepithelial lesion, there was an increased relative risk of 2.16 for the subsequent development of dysplasia (P < .01) (Table 4).
The overall rate of early cytologic abnormalities after LEEP in this study approaches 30%. This is consistent with that reported in the literature.10 Hanau et al10 looked at 162 LEEP patients and found an overall abnormal cytology rate of 33.3% with a mean length of follow‐up of 10.9 months. Margins were positive in 32.4% of their LEEP specimens.7,10 However, margins could not be accurately evaluated in approximately 30% of their patients, whereas in our study, only three (1%) patients were excluded because of indeterminate margins. The authors in this study also did not look at the rate of persistent histologically proven dysplasia. They concluded that prediction of follow‐up by marginal status was dubious.
The number of LEEP specimens with dysplasia involving the endocervical or ectocervical margins or endocervical glandular involvement was 50% and within the variable rate of 29–50% reported in the literature.4,5,7,9 Variability in the literature is probably a result of technique, the definition of positive margin used by the authors, and whether they included endocervical glandular or endocervical and ectocervical involvement with dysplasia. Although we were not able to identify a single statistically significant risk factor for abnormal initial cytology, we demonstrated that an increasing rate of residual dysplasia was associated with an increasing cumulative number of risk factors found on histologic evaluation of the LEEP specimen. We defined these risk factors as positive endocervical margin for dysplasia, positive ectocervical margin for dysplasia, or endocervical glandular involvement with dysplasia. The presence of these risk factors logically represents the impinging proximity of the lesion to the excision margin. Previous studies have documented the decreased specimen volume obtained with LEEP compared with conization.4,6 Previous reports have also cited severity of dysplasia in LEEP specimen and marginal status as risk factors for recurrent dysplasia.4,6,11 Histologic severity of dysplasia on the LEEP specimen, however, and individual marginal involvement were not independently associated with an increased risk of abnormal cytology or recurrent dysplasia in our study. Those patients, however, who developed abnormal cytology at initial follow‐up visit, were found to have up to twice the risk of persistent/ recurrent dysplasia after LEEP. The mean time to the development of recurrent dysplasia was also significantly shorter among those patients who had initial abnormal cytology after LEEP when compared with patients with normal cytology, 6 months versus 8 months, respectively.
The findings in this study are consistent with some of the previously published conclusions in the literature. Murdoch et al7 reviewed 721 LEEP patients. They noted that a histologic report of incomplete excision increased the risk of residual disease and was greatest when both endocervical and ectocervical margins were involved. Patients at their center who have positive margins are initially followed colposcopically for this reason.7 If initial follow‐up colposcopy is negative, they are discharged to routine care. We, however, noted no independent association between any single risk factor and abnormal initial follow‐up cytology or recurrent dysplasia. Also, the mean time to diagnosis of recurrent dysplasia in our population was 6 to 8 months after LEEP for those patients who had initial normal or abnormal cytology, respectively. As a result, a significant number of women who would eventually develop recurrent dysplasia would be missed if patients with normal cytology were eliminated from follow‐up based on an initial 3‐month cytologic evaluation. Particularly, patients with positive endocervical glandular involvement as their only risk factor for recurrence would be missed with this follow‐up schema. Livasy et al evaluated 248 patients after LEEP and found that positive margins, positive glands, and multiquadrant disease were all predictors of residual/ recurrent dysplasia and warranted close follow‐up with colposcopy.11 Our study's findings are most consistent with the latter; however, we did not find any association between severity of dysplasia and recurrence. Additionally, they did not comment on the interval of initial follow‐up after LEEP. We also did not observe any individual correlation between positive endocervical or ectocervical marginal status, endocervical glandular involvement, and abnormal initial follow‐up cytology or recurrent dysplasia. However, the presence of one or more risk factors found on LEEP specimen to include positive margins or endocervical glandular involvement with dysplasia increased the risk for recurrence.
Finally, it is important to note that 40% of our patients were not included in the final analysis of this study. However, the majority of the patients, 57%, were excluded because their initial follow‐up cytology occurred after the 3‐month interval prescribed by the study. These patients were not “lost to follow‐up” as they did have an evaluation within 6 months of their LEEP. Given that the study was performed to determine the optimal time and type of follow‐up analysis, it was necessary to exclude these patients. Therefore, those patients who were truly lost to follow‐up accounted for only 18% (89 of 509) of our population. The literature reports a lost to follow‐up rate of 20–30% after LEEP.10,11 Even a prospective study evaluating histologic follow‐up after LEEP had 13% of patients lost to follow‐up.8 The percentage of patients lost to follow‐up in our study was probably associated with the transient nature of the population involved in this study.
Based on our study, we propose the following scheme for the postprocedure management of women undergoing LEEP. Those patients who have cumulative evidence of endocervical marginal, ectocervical marginal, and endocervical glandular involvement with dysplasia on their LEEP specimens should have colposcopic evaluation with screening cytology at their initial follow‐up visit. This initial visit should take place at 6 months after LEEP, given the mean time for development of dysplasia in our study was 6.5 months. These patients are at increased risk for abnormal cytology and persistent dysplasia. As a result, performing colposcopic evaluation with screening cytology at initial 6‐month follow‐up quickly identifies these histologic abnormalities, and would save them an additional office visit. This decrease in office visits could positively impact compliance by decreasing any time away from job or family, and also decreasing the possibility of any discomfort that might be caused by the visits. Additionally, as in our population, if adequate follow‐up after cytologic evaluation cannot be assured, then colposcopic evaluation and treatment of high‐risk patients in a timely, organized, and prudent manner would ensure that patients with recurrent dysplasia would not go untreated. Thin‐prep cytology technique could also be considered for initial follow‐up evaluation of patients after LEEP, given the 14% of patients who had ASCUS on initial follow‐up cytology (Table 4). Future studies can be directed at developing a prospective randomized trial comparing cytological evaluation with colposcopic evaluation in patients undergoing LEEP.
1. Leusley D, Cullimore J, Redman C, Lawton F, Emens J, Rollason T, et al. Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears. BMJ 1990;300:1690–3.
2. Brigg A, Haffenden D, Sheehan A, Codling B, Read M. Efficacy and safety of large-loop excision of the transformation zone. Lancet 1994;343:32–4.
3. Ferris D, Hainer B, Pfenninger J, Zuber T, DeWitt D, Line R. Electrosurgical loop excision of the cervical transformation zone: The experience of family physicians. J Fam Pract 1995;41:337–44.
4. 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.
5. Simmons JR, Anderson L, Hernandez E, Heller P. Evaluating cervical neoplasia: LEEP as an alternative to cold knife conization. J Reprod Med 1998;43:1007–13.
6. Huang L, Hwang J. A comparison between loop electrosurgical excision procedure and cold knife conization for treatment of cervical dysplasia: Residual disease in a subsequent hysterectomy specimen. Gynecol Oncol 1999;73:12–5.
7. 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.
8. Baldauf J, Dreyfus M, Ritter J, Cuenin C, Tissier I, Meyer P. Cytology and colposcopy after loop electrosurgical excision: Implications for follow-up. Obstet Gynecol 1998;92:124–9.
9. Felix J, Muderspach L, Duggan B, Roman L. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol 1994;84:996–1000.
10. Hanau C, Bibbo M. The case for cytologic follow-up after LEEP. Acta Cytol 1997;41:731–6.
© 2002 The American College of Obstetricians and Gynecologists
11. Livasy C, Maygraden S, Rajaratnam C, Novotny D. Predictors of recurrent dysplasia after loop electrocautery excision procedure for CIN-3: A study of margin, endocervical gland and quadrant involvement. Mod Pathol 1999;12:233–8.