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Obstetrics & Gynecology 1999;93:359-362
© 1999 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Postpartum Regression Rates of Antepartum Cervical Intraepithelial Neoplasia II and III Lesions

NICOLE P. YOST, MD, JOSEPH T. SANTOSO, MD, DONALD D. MCINTIRE, PhD and FAWZI A. ILIYA, MD

From the University of Texas Southwestern Medical Center, Dallas, Texas, and the University of Texas Medical Branch at Galveston, Galveston, Texas.

Address reprint requests to: Nicole P. Yost, MD, 5323 Harry Hines Boulevard, Dallas, TX 75235-9032


   Abstract
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Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objective: To study the histologic regression and progression rates of cervical intraepithelial neoplasia (CIN) II and III after delivery and the effect the route of delivery has on the regression rates of CIN.

Methods: Pregnant patients with satisfactory colposcopic examinations and biopsy-proven CIN II and III were identified. Delivery information and postpartum biopsy results were obtained by chart review.

Results: Two hundred seventy-nine patients had antepartum biopsies of CIN II or CIN III. Of these, 126 women were excluded for the following reasons: lost to follow-up (75), human immunodeficiency virus positive (two), cesarean hysterectomy (four), and inadequate postpartum follow-up (45). This yielded a study group of 153 patients consisting of 82 with CIN II and 71 with CIN III. The regression rates were 68% and 70% among CIN II and CIN III patients (P = .78), respectively. Seven percent of patients with CIN II progressed to CIN III on postpartum evaluation. Twenty-five percent of those patients with CIN II and 30% of those with CIN III remained the same postpartum. No CIN lesions progressed to invasive carcinoma. There were no differences in regression rates or progression rates among the women who had vaginal deliveries (130), women who labored and then underwent cesarean (17), or women who proceeded to a cesarean without laboring (six).

Conclusion: We found similar high postpartum regression rates despite the route of delivery. We recommend conservative antepartum management with postpartum colposcopic evaluation regardless of route of delivery because we are unable to predict which of these lesions are more likely to regress.

Up to 5% of pregnancies are complicated by an abnormal Papanicolaou smear.1 The trend of managing abnormal Papanicolaou smears during pregnancy has changed over the decades from an aggressive approach with the more liberal use of conizations to a more conservative approach of observation. The more conservative approach is justified by several studies that document high regression rates of dysplasia in women after delivery.2,3 Furthermore, the rate of progression to invasive carcinoma over this short period of time is minimal. Using antepartum and postpartum cytologic evaluation, Kiguchi et al2 describe regression rates of 74.1% and 53.8% in moderate and severe dysplasia, respectively. The same authors reported only a 0.4% progression rate to invasive carcinoma.

The literature contains contradicting data about the influence the route of delivery has on dysplastic regression rates. Two publications reported the reduction in cervical cancer risk with cesarean delivery, with one study reporting a reduction of 40% for each cesarean.4,5 In contrast, a recent article reported a 0% regression rate among women with high-grade dysplasia who had undergone cesarean delivery, while those who delivered vaginally had a 60% regression rate.3

Our study had two goals. The first was to study the biopsy-proven, antepartum cervical intraepithelial neoplasia (CIN) II and CIN III lesions and their regression and progression rates postpartum. Our second goal was to resolve the issue of the effect that the route of delivery has on the regression rates of cervical dysplasia.


   Materials and Methods
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Abstract
 Materials and Methods
Results
 Discussion
 References
 
The study population consisted of all pregnant patients evaluated at the Parkland Memorial Health and Hospital System from February 1, 1995, to November 20, 1996. The patients, who were found to have low-grade or high-grade squamous intraepithelial lesion Papanicolaou smears, were referred to the Colposcopy Clinic for evaluation within 4 weeks of their initial Papanicolaou smears. We used the nomenclature of cytologic evaluation as proposed by the Bethesda system.6 Evaluation included a history, an obstetric examination, and a colposcopic assessment of the cervical epithelium before and after the application of 5% acetic acid. A satisfactory colposcopic examination was defined as visualization of the entire transformation zone and lesion. The most abnormal appearing epithelium was biopsied under colposcopic guidance. No effort was made to remove the entire lesion by biopsy. Furthermore, sampling of the endocervical canal was not performed.

Pregnant patients with biopsy-proven CIN II or CIN III on their initial evaluation were reevaluated at 28 to 32 weeks’ gestation for repeat Papanicolaou smear and colposcopic evaluation. A biopsy was repeated if worsening of the lesion was suspected colposcopically. Patients with antepartum CIN II and CIN III were reevaluated at 3 months and 6 weeks postpartum, respectively. Cervical cytology was performed and colposcopically guided biopsies were done as indicated. The grading of intraepithelial neoplasia was carried out as proposed by Richart and Barron.7 Postpartum regression of dysplasia was defined as complete normalization or downgrading from the antepartum histologic biopsy.

Statistical analysis was performed using Pearson {chi}2 and Breslow-Day statistic. The Breslow-Day statistic examines the equivalence of the association between degree of dysplasia and regression outcome across the route of delivery strata. P < .05 was considered statistically significant.


   Results
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Abstract
 Materials and Methods
 Results
Discussion
 References
 
During the study period, we identified 6628 colposcopic examinations, 1821 (27.5%) of which were performed on pregnant patients. From this pregnant population, 279 women met the inclusion criteria, which consisted of satisfactory colposcopic examinations with antepartum biopsies of CIN II or CIN III. Of the 279 patients, 126 were excluded for the following reasons: lost to follow-up (75), human immunodeficiency virus (HIV) positive (two), cesarean hysterectomy (four), or inadequate postpartum follow-up (45) (Figure 1Go). Inadequate follow-up consisted of those patients who were seen in the emergency room and did not have a colposcopic evaluation (22), those who were seen more than 1 year after delivery (19), and those whose histopathology was not graded (four).



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  		Figure 1. Distribution of patients who were included (study group) and excluded from the study. HIV = human immunodeficiency virus; C hyst = cesarean hysterectomy.

 
Consequently, our study group comprised 153 patients consisting of 82 patients with CIN II and 71 with CIN III. Table 1Go depicts the demographics of the study population. Antepartum cone biopsy or loop electrosurgical excision procedure was not performed in this group of patients. Immediately following cervical biopsy, no patients reported excessive bleeding (requiring vaginal packing, suture ligation, or blood transfusion) or premature labor (delivery before 37 completed weeks’ gestation).


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  		Table 1. Group-Specific Demographics
 
We found a similar high regression rate for patients with antepartum CIN II and CIN III (P = .78). The regression rates were 68% and 70% among CIN II and CIN III patients, respectively. A small proportion of patients with CIN II progressed to CIN III on postpartum evaluation (7%). A quarter of those patients with CIN II and approximately one third of those patients with CIN III remained the same postpartum. Most importantly, no patient progressed to invasive carcinoma (Table 2Go).


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  		Table 2. Regression and Progression Rates of Cervical Intraepithelial Neoplasia as a Function of Time
 
No statistical difference was found when the regression rates of the CIN II and CIN III groups were compared (P = .78). Subsequently, the CIN II and CIN III groups were each broken down into three separate groups by route of delivery, and regression rates were compared among these three groups. Again, no statistically significant difference was found in the regression rates between the CIN II and CIN III women who delivered vaginally, those who labored and then delivered by cesarean, and those who had a cesarean delivery without laboring (P = .53, Breslow-Day test).8 Therefore, we combined the CIN II and III groups into one large group and examined the regression rates among the three routes of delivery.

This compilation yielded 130 women who delivered vaginally, 17 who labored and then delivered by cesarean (12 were at least 4 cm dilated), and six who delivered by cesarean without laboring. Despite the different routes of delivery, there was no statistical difference in regression or progression rates (P = .74) among the three groups. Similar regression rates also were observed when all women who had cesarean delivery (23) were compared with the 130 women who had vaginal deliveries (P = .6) (Figure 2Go).



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  		Figure 2. Effect of delivery route on regression and progression rates of CIN II and CIN III. Vag = vaginal delivery; Labor + C = cesarean after laboring; C = cesarean without laboring.

 

   Discussion
Top
Abstract
 Materials and Methods
 Results
 Discussion
References
 
In our study, pregnant women with CIN II or CIN III showed similar high postpartum regression rates when delivered vaginally. Upon further evaluation, the regression rates appeared to be similar despite the different routes of delivery. However, this observation is not statistically significant because of the small sample size in the cesarean delivery groups. The most common explanation for this regression is the cervical trauma that occurs at the time of delivery. This leads to the desquamation of dysplastic cells and the subsequent cervical epithelium repair that takes place postpartum. A recent article reported regression rates after vaginal delivery that are similar to our findings.3

In contrast to our data, which are based on histologic evaluation, a recent article described a postpartum cytologic evaluation with a 0% regression rate in those women who had a cesarean delivery.3 This finding, which is in marked contrast from our findings, may be explained by the cervical trauma that occurred in the women who had undergone cesarean delivery after laboring.

Several other factors that may be responsible for the high regression rates in our cesarean delivery group include: the extensive metaplasia known to occur during pregnancy and postpartum, postpartum resolution of the immunosuppression believed to occur during pregnancy, the resolution of the enhanced expression of the human papillomavirus genome that appears to occur during the third trimester of pregnancy, and the removal of the lesion or a portion of the lesion by biopsy with the accompanying inflammatory process that may enhance the dysplastic resolution process.4,9

Histologic evaluation of colposcopically directed biopsies in the pregnant patient is superior to colposcopic examination alone. Economos et al10 reported a high misdiagnosis rate when colposcopic evaluation was done alone without directed biopsies in pregnancy. Fifty-four percent of colposcopic examinations thought to be normal were in fact CIN I or CIN II upon histologic evaluation, and 14% of those with colposcopic impressions of CIN I were actually CIN III. This discrepancy may be explained by the numerous cervical changes known to occur during pregnancy making colposcopy more difficult. Furthermore, even the most expert colposcopist achieves an accuracy of only 85% when predicting final histology.1,11 This study attests to the safety of performing cervical biopsies during pregnancy as has been the practice in our colposcopy clinic for many years. This has been supported by other studies.10,12

There were no patients in our study with CIN II or CIN III who progressed to invasive carcinoma. Thus, our findings support conservative management of those patients with CIN II or CIN III during pregnancy. Although many of these patients will not require post-partum intervention, we still recommend postpartum colposcopic evaluation regardless of the route of delivery because we are unable to predict which CIN II or CIN III lesions are more likely to regress.


   Footnotes
 
PII S0029-7844(98)00483-9

Received June 15, 1998. Received in revised form September 16, 1998. Accepted September 24, 1998.


   References
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Abstract
 Materials and Methods
 Results
 Discussion
 References
 
1. Campion MJ, Sedlacek TV. Colposcopy in pregnancy. Obstet Gynecol Clin North Am 1993;20:153–63.[Medline]

2. Kiguchi K, Bibbo M, Hasegawa T, Kurihara S, Tsutsui F, Wied G. Dysplasia during pregnancy: A cytologic follow-up study. J Reprod Med 1981;26:66–72.[Medline]

3. Ahdoot D, Van Nostrand KM, Nguyen NJ, Tewari DS, Kurasaki T, DiSaia PJ, et al. The effect of route of delivery on regression of abnormal cervical cytologic findings in the postpartum period. Am J Obstet Gynecol 1998;178:1116–20.[Medline]

4. Brinton LA, Reeves WC, Brenes MM, Herrero R, de Britton RC, Gaitan E, et al. Parity as a risk factor for cervical cancer. Am J Epidemiol 1989;130:486–96.[Abstract/Free Full Text]

5. Bosch FX, Munoz N, de Sanjose S, Izarzugaza I, Gili M, Viladiu P, et al. Risk factors for cervical cancer in Columbia and Spain. Int J Cancer 1992;52:750–8.[Medline]

6. Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH. National Cancer Institute workshop 1992. Interim guidelines for management of abnormal cervical cytology. JAMA 1994;271: 1866–9.[Medline]

7. Richart RM, Barron BA. A follow up study of patients with cervical dysplasia. Am J Obstet Gynecol 1969;105:386–93.[Medline]

8. Breslow NE, Day NE. The analysis of case-control studies. In: Statistical methods in cancer research, volume I—The analysis of case-control studies. Lyon: IARC Scientific Publications, No. 32, 1980:142–6.

9. Rock JD, Thompson JA. Te Linde’s operative gynecology, 8th ed. Philadelphia: Lippincott-Raven, 1997:1403.

10. Economos K, Veridiano NP, Delke I, Collado ML, Tancer ML. Abnormal cervical cytology in pregnancy: A 17-year experience. Obstet Gynecol 1993;81;915–8.[Abstract/Free Full Text]

11. Powell JL. Pitfalls in cervical colposcopy. Obstet Gynecol Clin North Am 1993;20:177–88.[Medline]

12. LaPolla JP, O’Neill C, Wetrich D. Colposcopic management of abnormal cervical cytology in pregnancy. J Reprod Med 1988;33: 301–6.[Medline]




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