European Journal of Obstetrics & Gynecology and Reproductive Biology 104 (2002) 67–69
Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum Evangelos Paraskevaidis*, George Koliopoulos, Sophia Kalantaridou, Lambrini Pappa, Iordanis Navrozoglou, Kostas Zikopoulos, Dimitrios E. Lolis Department of Obstetrics & Gynecology and Cytology Laboratory, Ioannina University Hospital, Ioannina, Greece Received 1 January 2002; accepted 18 February 2002
Abstract Objective: To investigate the evolution of cervical intraepithelial neoplasia (CIN), and to evaluate the safety of cytological and colposcopical surveillance of women with CIN during pregnancy. Study design: Ninety-eight women with antenatal cytological and/or colposcopical impression of CIN were followed up during pregnancy with cytology and colposcopy every 2 months. A cytological and colposcopical reevaluation 2 months postpartum was done, and large loop excision of the transformation zone (LLETZ) was performed if appropriate. Punch or loop biopsies were only taken if there was suspicion of microinvasion. Results: In 14 of 39 (35.9%) and in 25 of 52 (48.1%) women with antenatal impression of CIN I and CIN II–III, respectively, there was postnatal impression of regression. Seven women with findings suspicious of microinvasion underwent small loop biopsies during pregnancy, but early stromal invasion (<1 mm) was seen in just one case. There was one more case of microinvasion (1.5 mm) diagnosed postnatally in which the antenatal impression was of CIN III. 84.6% of the women with regression compared to 67.3% of the women with stable disease or progression had a vaginal delivery (P ¼ 0:057). Conclusion: There is a considerable regression rate of CIN after pregnancy possibly attributable to the loss of the dysplastic cervical epithelium during cervical ripening and vaginal delivery. Frequent cytological and colposcopical evaluation seems to be safe. Small loop biopsies are recommended in cases of possible microinvasion. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Pregnancy; CIN; Cytology and colposcopy
1. Introduction Colposcopic evaluation during pregnancy can be usually performed without great difficulty even in advanced gestational age using a four-blade speculum to control a normal vaginal prolapse, and it is usually satisfactory due to a peripheral transposition of the transformation zone of the cervix [1]. Apart from women who during their routine follow up after treatment of cervical intraepithelial neoplasia (CIN) become pregnant and need to be examined colposcopically, there are two other groups of women who during their pregnancy need to be attended with cytology and colposcopy. One group consists of women who had an abnormal result on a cervical smear taken during their first antenatal visit and need to be referred for colposcopy. The other group consists of women who had an abnormal Pap smear result and abnormal colposcopical or histological findings, but become pregnant while awaiting treatment. * Corresponding author. Tel.: þ30-113-651-99515; þ30-113-651-99788. E-mail address:
[email protected] (E. Paraskevaidis).
The aim of this study was to investigate the evolution of CIN in pregnancy as well as to evaluate the safety of cytological and colposcopical surveillance of pregnant women with CIN.
2. Materials and methods A total of 269 pregnant women who attended the colposcopy outpatient clinic of our Hospital between 1990 and 2000 were retrospectively studied. The referral criteria for colposcopy in our setting were a single report of high-grade squamous intraepithelial lesion (SIL) or persistent report of a smear suggestive of atypical squamous cells of undetermined significance (ASCUS) or low-grade SIL within a period of 3–6 months. Our treatment policy was selective ‘‘see and treat’’ without previous punch biopsies preferably at the follicular menstrual stage and the method of treatment was large loop excision of the transformation zone (LLETZ). Thirty-four women who had been evaluated shortly before menstruation and were scheduled for treatment following the end of the next menstruation returned being
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pregnant (Group A). Sixty-seven women had an abnormal result of dyskaryosis on the smear taken at the first antenatal visit (Group B). The intention in the women of groups A and B was not to take any biopsies and to withhold treatment until delivery. Repeated evaluation every 2 months was done with cytology and colposcopy. In women with no evidence of invasion, a meticulous cytological and colposcopical reevaluation 2 months postpartum was done, and LLETZ was performed if appropriate about a month later. The most severe antenatal impression was compared to the postnatal impression and the lesion was characterized as progression, stable or regression accordingly. Progression was characterized in any case where there were either cytological or colposcopical indications of progression of the lesion. Regression was characterized any case with cytological and colposcopical indications of regression. Only in cases with antenatal cytologic and/or colposcopic impression of a lesion worse than CIN III, a small loop biopsy was taken from the most colposcopically abnormal area to ensure histological diagnosis. One hundred thirty-six women were self-referred or referred by their obstetrician or cytologist with a Pap smear suggestive of HPV infection without dyskaryosis, because of the uncertainty around the evolution of HPV infection during pregnancy and the optimal mode of delivery (Group C). Follow up after 6 months, which was usually in advanced gestational age, was arranged in these women if colposcopy was not suggestive of CIN. If colposcopy was indicative of CIN, the women were followed up with cytology and colposcopy as in groups A and B. Finally, there were 32 pregnant women who were referred with clinical condylomata of the lower genital tract or perineum (Group D). This group of women was treated with laser ablation and follow up was arranged after 1 month and 1 month before the estimated date of delivery. Statistical analysis of findings was done with chi-square test.
3. Results Of the 136 women with HPV infection only in their smears (group C), 14 had colposcopic impression of CIN and attended every 2 months as in groups A and B. In 122 women, colposcopy was either normal or suggestive of HPV
infection only. They were given follow up appointments after 6 months, which 97 women attended without anyone presenting with indications of progression. Thirty-four women from group A, 67 women from group B and 14 women with abnormal colposcopy from group C were reviewed every 2 months (total 115). Of the 67 women with abnormal smears (group B), 13 had normal colposcopy, however, they remained under close surveillance every 2 months. Seventeen of the 115 defaulted follow up and the remaining 98 had cytology and colposcopy every 2 months. In 83 of 98 (84.6%) women, the first and last antenatal impression was the same. The most severe antenatal impression and the postnatal impression are given in Table 1. In 14 of 39 (35.9%) women with antenatal impression of CIN I and in 25 of 52 (48.1%) women with antenatal impression of high-grade lesion there was postnatal impression of regression. Seven women who during pregnancy had findings suspicious of microinvasion, underwent small loop biopsies and the histological report was decidual reaction in five cases, CIN III in one and early stromal invasion (<1 mm) in one more, a primigravida at 26 weeks gestation. The last woman continued with pregnancy, fully informed on the natural history of cervical carcinogenesis, and delivered at 37 weeks gestation after induction of labor. Six weeks later, LLETZ was performed and histology revealed microinvasive cervical carcinoma excised on clear margins [2]. There was one more case of microinvasion (1.5 mm) diagnosed postnatally in which the antenatal impression was of highgrade lesion (Table 2). Of the 98 women with abnormal antenatal findings 66 (67.3%) underwent LLETZ, because of they still had abnormal findings in the postnatal evaluation. The histological results in the patients that had a LLETZ postnatally are shown in Table 2. In 11 of them, postnatal histology was less than CIN and should be considered as overtreatment. Of the 39 women with regression 33 (84.6%) had a vaginal delivery and 6 (13.4%) a cesarean section, while of the 52 women with stable disease or progression 35 (67.3%) had a vaginal delivery and 17 (32.7%) had a cesarean section (P ¼ 0:057). Thirty-one of 32 women with condylomata (group D) were treated with laser ablation. For 24 (77.4%), this was the definitive treatment. Six required further treatment and one did not return for follow up. Twenty-three women delivered vaginally, six had a cesarean section for obstetrical reasons,
Table 1 Ante- and postnatal cytological and colposcopical impression in 98 women Antenatal impression
CIN I (n ¼ 39) CIN II–III (n ¼ 52) Possible microinvasion (n ¼ 7) Total (n ¼ 98) a
Decidual reaction.
Postnatal impression Nil
HPV
CIN I
CIN II–III
Microinvasion
8 5 5a 18
6 8 0 14
23 12 0 35
2 26 1 29
0 1 1 2
E. Paraskevaidis et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 104 (2002) 67–69
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Table 2 Histological results in the 67 patients that had a loop excision postnatally in correlation to the antenatal impression Antenatal impression
CIN I (n ¼ 25) CIN II–III (n ¼ 39) Microinvasion (n ¼ 2)a Total (n ¼ 66) a
Histology Less than CIN
CIN I
CIN II–III
Microinvasion
8 3 0 11
16 13 0 29
1 22 1 24
0 1 1 2
Five women with decidual reaction on the small loop performed antenatally are excluded.
and for one there are no data available since she moved from the area. 4. Discussion According to the results of this study there is a considerably high rate of regression of CIN after delivery. The regression rate of 35.9% for CIN I found in this study is double than the regression rate for CIN I found in a previous study on non-pregnant women [3]. This finding is in accordance with other studies in which pregnant women were followed up with colposcopy and punch biopsies [4,5]. In our study, however, punch or loop biopsies, which have been shown to alter the natural history of CIN through a local inflammatory reaction and therefore might cause the regression [6,7], were not performed unless there was suspicion of microinvasion (seven cases). Having excluded punch biopsies as a possible cause of regression, the fact that after vaginal delivery the rates of regression were higher, a finding which is in contrast to another study [5], possibly suggests that the regression is not attributable to the pregnancy itself, but to the loss of the dysplastic cervical epithelium during cervical ripening and vaginal delivery. Although LLETZ is a more conservative method than cold knife conization, it has not been shown to cause less complications than cold knife conization during pregnancy [8]. It is therefore recommended to minimize treatment interventions for CIN in pregnancy, not because of the possibility of regression postpartum, but mainly in order to avoid the serious complications of a procedure such as severe hemorrhage, chorioamnionitis, preterm labor and fetal loss [9]. On the other hand colposcopic and cytological surveillance of cervical lesions during pregnancy seems to be safe. The fact that the majority of pregnant women are young along with the transposition of the transformation zone to the periphery of the cervix associated with pregnancy are the main reasons why colposcopy is usually satisfactory in pregnancy. Only in two cases was final histology worse than the antenatal impression (Table 2). There were no cases of invasive carcinoma diagnosed postnatally, although there was one case of microinvasion in which the antenatal impression was of CIN III. While the possibility of infiltration of the basal membrane and stromal invasion occurring during pregnancy cannot be excluded, it is more likely that the microinvasion pre-existed from the beginning of pregnancy despite frequent cytological
and colposcopical evaluations. It is possible that in some of the 14 women with postnatal impression of subclinical HPV infection only, and despite the agreement of both cytology and colposcopy, a more severe lesion might be underlying (Table 1). Therefore, this group of women should remain under close surveillance for a short period. In some cases a decidual reaction might confuse an unexperienced colposcopist. A loop biopsy using the smallest electrode can be used for histological verification in uncertain cases with safety, since we did not encounter any bleeding in our cases. Although it is sometimes tempting to use a normal sized loop electrode to perform even a shallow loop excision of the transformation zone, this is not recommended since the risk of severe bleeding and the possibility of incompletely excising the lesion, resulting in a second procedure postnatally are rather high. A thoughtful decision to use the smallest loop wire, which ensures enough tissue depth to examine possible microinvasion, instead of the conventional punch biopsy, seems the more rational approach.
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