The Management of Cervical Intraepithelial Neoplasia During Pregnancy: Is Colposcopy Necessary?

Luisa A. Wetta, MD, Kellie S. Matthews, MD, Meredith L. Kemper, MD, Jenny M. Whitworth, MD, Emily T. Fain, Warner K. Huh, MD, James E. Kendrick, MD, and J. Michael Straughn, Jr., MD
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL

h Abstract
The 2006 American Society for Colposcopy and Cervical Pathology Consensus guidelines state that it is acceptable to defer colposcopy until 6 weeks postpartum in pregnant patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology. Therefore, we sought to determine the incidence of cervical intraepithelial neoplasia (CIN) 2,3 in pregnant patients referred to a university colposcopy clinic. Materials and Methods. A retrospective study identified all pregnant women with abnormal cytology referred to the University of Alabama at Birmingham colposcopy clinic between May 2005 and September 2007. After an institutional review board approval was obtained, demographic information, referral cytology, and histologic data were collected. The colposcopic impression was also obtained from the records. Results. Six hundred twenty-five pregnant patients were identified. The mean age was 23 years (range, 14Y44 years), the mean parity was 1 (range, 0Y7), and the mean gestational age was 24 weeks (range, 4Y39 weeks). The most common referral cytology was LSIL (41.0%), followed by ASC-US (34.1%), and high-grade squamous intraepithelial lesion (13.6%). One hundred thirty-eight
Objective.

patients (22%) underwent cervical biopsy at the time of initial colposcopy. Forty-three patients had CIN 1, 28 patients had CIN 2, and 23 patients had CIN 3. Fortyfour patients (32%) had no evidence of CIN on biopsy. There were no cases of invasive cervical cancer identified. Of the 469 patients with ASC-US and LSIL cytology, 20 of 78 patients who had a cervical biopsy were diagnosed with CIN 2,3. Of the 128 patients with high-grade intraepithelial lesion or high-grade squamous intraepithelial lesion cytology, 31 of 60 patients who had a cervical biopsy were diagnosed with CIN 2,3. Repeat colposcopy in the third trimester was performed on 47 patients. Only 3 of 13 patients with a repeat biopsy had CIN 2,3. Conclusions. Pregnant patients with ASC-US or LSIL cytology rarely have colposcopically suspected CIN 2,3 at their initial colposcopy that warrants a cervical biopsy; therefore, it is reasonable to defer the initial colposcopy in patients with ASC-US and LSIL until at least 6 weeks postpartum. h
Key Words: colposcopy, pregnancy, abnormal cytology, CIN

Reprint requests to: Luisa A. Wetta, MD, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 618 South 19th Street, Old Hillman Building 549, Birmingham, AL 35233. E-mail: Luisa.Wetta@ obgyn.uab.edu

2009, American Society for Colposcopy and Cervical Pathology Journal of Lower Genital Tract Disease, Volume 13, Number 3, 2009, 182Y185

ervical cytologic screening is a routine element of prenatal care, despite the extremely low incidence of cervical cancer in pregnancy (1 in 1,200 to 1 in 2,500 pregnancies) [1, 2]. Although pregnancy affords the opportunity for cancer screening, it is unknown if the diagnosis of cervical neoplasia affects the clinical outcome of a pregnant patient [3]. For example, it has been shown that pregnancy does not seem to increase the progression of invasive cervical cancer or worsen the prognosis. In addition, it is unclear if pregnancy

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affects patients with cervical intraepithelial neoplasia (CIN) [4]. Although colposcopy is a safe and effective method of evaluating abnormal cervical cytology in pregnant patients, many physicians prefer to refer these patients to a specialist [5]. The goal of colposcopy during pregnancy is to identify microinvasive or invasive disease; however, the incidence of cancer is quite low [4, 6]. Women diagnosed with CIN 2,3 are managed conservatively with observation because progression to invasive disease is unlikely [7]. As a result, studies have supported a conservative approach to the management of CIN during pregnancy, especially in patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology [7Y10]. The 2006 American Society for Colposcopy and Cervical Pathology (ASCCP) Consensus guidelines state that it is acceptable to defer colposcopy until 6 weeks postpartum in pregnant patients with ASC-US or LSIL cytology [6]. For most patients with no colposcopic or histologic evidence of CIN 2,3 or invasive carcinoma, postpartum follow-up is the preferred management. Our goal was to determine the incidence of CIN 2,3 and invasive cancer in pregnant patients referred to a university colposcopy clinic.

management was evaluated and included postpartum treatment, repeat antepartum colposcopy, or postpartum Pap smear. Follow-up histology was recorded if available. During the study period, all Pap smears and cervical biopsies were processed and evaluated by university-based cytopathologists. Cervical-directed biopsies were interpreted using standard histologic descriptions of CIN 1, CIN 2, or CIN 3.

RESULTS
A total of 625 pregnant patients were identified. Most patients were black (55.9%), and the mean age was 23 years. Mean parity was 1, and mean gestational age was 24 weeks. The most common referral cytology was LSIL (41.0%) followed by ASC-US (34.1%). Patient demographics are depicted in Table 1. One hundred thirty-eight (22%) of pregnant patients underwent cervical biopsy at the time of initial colposcopy based on colposcopic impression of the colposcopist. Of the 138 patients biopsied, 43 (31.2%) patients had CIN 1, 28 (20.3%) patients had CIN 2, and 23 (16.7%) patients had CIN 3. Forty-four (31.8%) patients biopsied had no evidence of CIN on biopsy. No cases of invasive cancer were identified. The relationship of referral cytology to histologic biopsy is shown in Table 2. Of 469 patients with ASC-US or LSIL referral cytology, only 78 patients underwent a cervical biopsy. Thirty-one (39.7%) patients had CIN 1, whereas
Table 1. Patient Demographics
Characteristic Race White Black Other Age, y Mean Range Parity Mean Range Gestational age, y Mean Range Referral cytology ASC-US LSIL HSIL ASC-H AGC Unknown N (%)

PARTICIPANTS AND METHODS

After approval by the Institutional Review Board, a retrospective chart review was performed of pregnant women referred to the University of Alabama at Birmingham colposcopy clinic for abnormal cervical cytology. Patients were identified by a computerized database and were evaluated between May 2005 and September 2007. The patients were primarily managed by surrounding health departments, private practitioners, and university-based clinics. Referrals were based on abnormal cytology including ASC-US; ASC cannot exclude high-grade intraepithelial lesion (ASC-H), LSIL, high-grade squamous intraepithelial lesion (HSIL), or atypical glandular cells (AGC). All patients underwent a colposcopic examination with or without directed biopsy depending on the colposcopic impression. A gynecologic oncologist performed colposcopic examinations. Demographic information, referral cytology, colposcopic impression, and histologic data were collected from the chart. Colposcopic impression was classified as normal, CIN 1, CIN 2, CIN 3, or cancer. Postcolposcopy

184 (29.4%) 349 (55.9%) 92 (14.7%) 23 14Y44 1 0Y7 24 4Y39 213 (34.1%) 256 (41.0%) 85 (13.6%) 43 (6.9%) 1 (0.0%) 27 (4.3%)

ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; ASC-H, high-grade intraepithelial lesion; AGC, atypical glandular cells.

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Table 2. Relationship of Referral Cytology to Histologic Biopsy

Histology Referral cytology ASC-US LSIL ASC-H HSIL Total Negative 7 20 4 13 44 (31.9%) CIN 1 8 23 0 12 43 (31.2%) CIN 2 6 8 3 11 28 (20.3%) CIN 3 3 3 3 14 23 (16.7%) Total 24 54 10 50 138 (100%)

CIN, cervical intraepithelial neoplasia; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; ASC-H, high-grade intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion.

20 (25.6%) patients had CIN 2,3. Twenty-seven (34.6%) patients had negative biopsies. Of 128 patients with ASC-H or HSIL cytology, 60 patients had a cervical biopsy. Twelve (20.0%) patients had CIN 1, and 31 (51.7%) patients had CIN 2,3. Seventeen (28.3%) patients had a negative biopsy. Repeat colposcopy in the third trimester was performed on 47 patients; 13 patients underwent a repeat biopsy. Three patients had biopsy-proven CIN 2,3, and no patients had progression of disease documented on repeat colposcopy.

DISCUSSION
The 2001 ASCCP guidelines recommended colposcopy for all pregnant patients with abnormal cervical cytology, regardless of the degree of abnormality [6]. This recommendation was based on previous studies that supported the safety and efficacy of colposcopy for pregnant women [5, 11, 12]. The 2006 ASCCP guidelines now state that colposcopic evaluation of ASC-US or LSIL cytology can be delayed until 6 weeks postpartum [6]. This change was based on evidence that women with ASC-US or LSIL cytology rarely have biopsy-proven CIN 2,3 at the time of initial evaluation and are at low risk for the development of invasive cervical cancer during pregnancy [13]. In a study by Jain et al., prenatal colposcopy was performed on women with LSIL (220 patients) and ASC-US (33 patients) cytology. Sixty-seven patients underwent a biopsy. None of the 7 women biopsied with ASC-US cytology had CIN 2,3. In the 60 women biopsied with LSIL, only 6 (10%) had a biopsy consistent with CIN 2,3. During postpartum follow-up, no women were found to have invasive cervical cancer [1]. Fortunately, patients who are diagnosed with CIN 2,3 during pregnancy rarely will require treatment or a change in their obstetrical management [14]. In a study

of 208 pregnant women by Vlahos et al., 78 patients with biopsy-proven CIN 2,3 were followed with colposcopy every 8 to 10 weeks and at 6 weeks postpartum. Forty-eight patients had regression to CIN 1. Thirty patients had persistence of CIN 2,3; however, no patients experienced progression of disease, and no cases of invasive cervical cancer were identified [7]. In our study, only 20 (25.6%) of 78 patients biopsied with LSIL or ASC-US cytology had CIN 2,3. In contrast, 31 (51.6%) of 60 patients biopsied with HSIL or ASC-H cytology had CIN 2,3. The findings of our study are consistent with previous studies that demonstrated an overall low incidence of CIN 2,3 in patients with ASC-US or LSIL cytology. Similar to previous studies, we found no incidence of invasive cervical malignancy. Although 51% of patients with HSIL or ASC-H cytology had biopsy-proven CIN 2,3 at the time of initial colposcopy, reevaluation in the third trimester did not find new cases of CIN 2,3 or progression of disease. Therefore, a repeat colposcopic examination during the third trimester rarely alters the clinical management of the patient and may only increase patient anxiety, discomfort, and cost. Although this is a large single institution study, there are a number of limitations. Due to the low incidence of cervical cancer in pregnancy, it is unlikely that we would detect a case of invasive cancer in a population of 625 patients. Because only 78 patients with ASC-US or LSIL cytology underwent cervical biopsy, it is likely that some cases of CIN may have been missed. Furthermore, using random biopsies of the cervix instead of colposcopic impression would have detected more cases of CIN. Finally, only 47 patients underwent repeat colposcopy during the pregnancy, limiting our ability to detect all cases of disease progression. These results support the 2006 consensus guidelines to defer colposcopy until 6 weeks postpartum in patients with LSIL or ASC-US cytology. Our findings also suggest that colposcopic evaluation of pregnant patients with HSIL and ASC-H could potentially be delayed until the postpartum period because invasive malignancies are extremely rare. Furthermore, repeat colposcopy of patients with CIN 2,3 during pregnancy is unnecessary because it rarely impacts the clinical management of the pregnant patient.

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