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High-grade Cervical Squamous Intraepithelial Lesion during Pregnancy

Article in Tumori Journal · May 2002

DOI: 10.1177/030089160208800312 · Source: PubMed

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Tumori, 88: 246-250, 2002
HIGH-GRADE CERVICAL SQUAMOUS INTRAEPITHELIAL LESION DURING
PREGNANCY
Eddie Fernando Candido Murta, Flavio Henrique Caetano de Souza, Maria Azniv Hazarabedian de Souza,
and Sheila Jorge Adad
Discipline of Gynecology and Obstetrics, Faculty of Medicine of "Tritingulo Mineiro", Uberaba MG, Brazil
Aims and background: An increasing incidence of high-grade
squamous intraepithelial lesion (HSIL) has been observed
among young women. Consequently, an increased number of
cases are being discovered during pregnancy. We analyzed
the clinical and therapeutic management of HSIL during preg-
nancy.
Methods: A retrospective study was conducted from 1979 to
1998, and 58 registries of women with a cytological or histo-
logical diagnosis of HSIL during the pregnant-puerperal peri-
od were reviewed. Information obtained from medical records
included age, gestational age at diagnosis, parity, age of first
intercourse, number of sexual partners before pregnancy, to-
bacco use, cytologic and colposcopic findings, route of deliv-
ery, postpartum follow-up, and treatment. This information
was compared with a non-pregnant control group with HSIL.
Results: The average age of pregnant women with HSIL was
27.9 ± 5.2 years. The cytologic or histologic diagnosis of HSIL
was made in the first trimester in 12 (20.7%) women and in the
Key words: biopsy, conservative treatment, delivery, high-grade squamous intraepithelial lesion, pregnancy.
Introduction
Cervical carcinoma is the most common cancer asso-
ciated with pregnancy'. In the last years, an increasing
incidence of cervical intraepithelial neoplasia (CIN) has
been observed among young healthy women-? and
those with human immunodeficiency virus infection".
Consequently, an increasing number of cases are dis-
covered during pregnancy. A 0.93% to 5% incidence of
CIN in pregnancy has been described-I:". During preg-
nancy, the most common cervical abnormalities are
classified as low-grade squamous intraepithelial
lesions"!'. Apparently, pregnancy is not a risk for the
development of CIN because its incidence is similar to
that of non-pregnant women l ,7,ll , l 2. The progression rate
of CIN becoming invasive cancer during pregnancy is
low, and there are no data to indicate that CIN progress-
es more rapidly to an invasive cancer in the pregnant
state than in the non-pregnant state 8,13.
The regression rate to normal of high-grade squa-
mous intraepitheliallesions (HSIL) ranges from 12%8,9
to 53.5%14. Different treatments have been proposed
over the years, including hysterectomy, cold knife or
laser conization, loop electrosurgical excision procedure
(LEEP), and a close follow-up schedule'>!". The last
one has been proposed during pregnancy by several au-
Acknowledgments: We are grateful to Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) for research support.
Correspondence to: Eddie Fernando Candido Murta, Rua Alfen Paixao, 170 Apto. 202, 38.060-230, Uberaba MG, Brazil. Tel 55-34-3318-5326;
fax 55-34-3318-5342; e-mail eddiemurta@mednet.com.br
Received Apri127, 2001; accepted January 29, 2002.
second trimester in 30 (51.7%) women. Average parity was 2.8
± 2 deliveries. Age of first intercourse ranged from 13 to 29
years (16.1 ± 3.3). Thirty-two women (55.1%) had more than
one sexual partner before pregnancy. Thirty-seven (63.8%) ref-
ereed tobacco use. According to the aforementioned aspects,
no statistical difference was found in relation to control, ex-
cept to cervical ectopia, which was more frequent in pregnant
women (56.9% versus 42.6%). From the total of 58 pregnant
women with cytologic or biopsy HSIL diagnosis, 53 had HSIL
diagnosis made on cervical biopsy directed by colposcopy
performed during the pregnancy; 44 (83%) of them were sub-
mitted to conservative management. HSIL was diagnosed by
cervical biopsy in postpartum evaluation in 76% pregnant
women with vaginal delivery and 78.6% women who under-
went cesarean section.
Conclusions: A conservative management of HSIL in pregnancy
is proposed, with colposcopic evaluation during gestation
and postpartum, regardless of route of delivery.
thors who maintain that conization should be avoided
because of the high risk of maternal and fetal complica-
tions and that, after delivery, the surgical treatment is
done 9 ,15,17. Our objective is to contribute to this prob-
lem. We analyzed the clinical and therapeutic manage-
ment of HSIL during pregnancy.
Patients and methods
Patients
A retrospective study was conducted from 1979 to
1998, and 511 cases of HSIL were diagnosed, with 58
(11.3%) during the pregnant-puerperal period. In the
same period, 169 cases of invasive cancer were diag-
nosed, and 7 (4,1%) occurred during the pregnancy. We
considered the pregnant-puerperal period until 12 months
postpartum. A random control group with 68 non-preg-
nant women with HSIL diagnosed by cytology or/and
biopsy was used for comparison of epidemiological data,
cytological and colposcopical findings, and histology.
Methods
The information obtained from medical records in-
cluded: age, gestational age at diagnosis, parity, age of
 HSIL DURING PREGNANCY 247

the first intercourse, number of sexual partners before Table 2 - Distribution of 58 pregnant women and 68 non-preg-
nant women according to colposcopic findings
pregnancy, tobacco use, cytologic and colposcopic find-
ings, route of delivery, postpartum follow-up, and type Pregnant Not pregnant
of treatment. No patients were treated during the preg- Findings No. % No. %
nancy. All cytologies and biopsies were reviewed. Cyto-
logic findings were classified according to the Bethesda WP 28 48.3 22 32.3
M I 1.7 0 0
Systerrr". Colposcopy was performed after 3% acetic P 3 5.2 4 5.9
acid application, the Schiller test and Bissulfito applica- WP+M 8 13.8 II 16.2
WP+P 7 12 17 25
tion; it was considered unsatisfactory when the squa- M+P 3 5.2 3 4.4
mous-columnar junction could not be seen. We utilized WP+M+P 8 13.8 II 16.2
the nomenclature cited by Stafl and Wilbanks?'. Coniza- Total 58 100 68 100
tion and LEEP were used for the postpartum treatment WP: white epithelium; M: mosaic; P: punctation.
of HSIL. The criteria for LEEP were a small lesion, a
visible squamous-columnar junction, and desire of fu-
ture gestation.
<0.09; odds ratio, 1.952, marginally significant). Punc-
Statistical analysis tation was found in 35 (51.5%) cases of non-pregnant
The chi-squared test with Yates correction, the Fisher women versus 21 (36.2%) in pregnant women (P <0.06;
test, and Student's t test were used for statistical analy- odds ratio, 0.535, marginally significant). The associa-
sis. tion of two or more findings was more frequent in
non-pregnant women, with 42 (61.8%) cases versus 21
Results (36.2%) from the control group (P <0.05; odds ratio,
0.503). There was no case of unsatisfactory colposcopy
A total of 58 pregnant women with a cytologic or his- in either group.
tologic diagnosis of HSIL were analyzed. The diagnosis
of HSIL was made in the first trimester in 12 (20.7%) Biopsy evaluation in pre- and postpartum
women, in the second trimester in 30 (51.7%) women, From the total of 58 pregnant women with a cytologi-
and in the last trimester in 16 (27.6%) women. The dis- calor biopsy diagnosis of HSIL, one (1.7%) had an inva-
tribution of age, age of the first intercourse, parity, num- sive carcinoma in the cervical biopsy performed during
ber of sexual partner and tobacco use in gestational and pregnancy (stage IB, diagnosed in the second trimester
control group are reported in Table 1. No statistical dif- of gestation). She was submitted to an induced abortion,
ference was found between the groups. radiotherapy and Wertheim Meigs. Four women (6.9%)
underwent biopsy after delivery: 1 had normal cytologic
Colposcopic evaluation and colposcopic evaluations, and the other 3 had an inva-
Ectopia was presented in 29 (42.6%) cases in the sive carcinoma. A total of 53 women (91.4%) had the di-
control group compared to 56.9% of prenatal evaluation agnosis of HSIL made on cervical biopsy directed by
in the gestational group (P = 0.07; odds ratio, 0.563, colposcopy performed during the pregnancy. One
marginally significant). Colposcopic findings are shown woman aborted some weeks after biopsy.
in Table 2. All findings were classified as major Of the 53 patients, 44 (83%) women were submitted
changes. No statistically significance was found when a conservative treatment with a cytological and colpo-
all findings were analyzed together. The isolated analy- scopical evaluation in postpartum. Table 3 shows the
sis of white epithelium as the only finding showed that distribution of 44 pregnant women who underwent cer-
it was more frequent in the pregnant group, with 28 vical biopsy according to cytology and histology during
(48.3%) cases versus 22 (32.3%) in the control group (P pregnancy and postpartum. The diagnosis of HSIL was

Table 1 - Distribution of age, age of first intercourse, parity, Table 3 - Distribution of 44 pregnant women submitted to cer-
number of sexual partners and tobacco use in the pregnant vical biopsy according to cytology (Cyt) and histology (Hyst)
women (n == 58) and control group (n = 68) with HSIL before and postpartum
Pregnant women Control group Prenatal evaluation Postpartum evaluation
Mean Range Mean Range Vaginal Cesarean
Age (yr) 27.9 ± 5.2 16-39 30.6 ± 7.8 17-54 Diagnosis Cyt Hyst Cyt Hyst Cyt Hyst
Age of first intercourse (yr) 16.1±3.3 13-29 16.8 ± 4.2 13-44
Parity 2.8 ± 2 0-10 2.6 ± 1.9 0-9 WithoutCIN 2 3
Ascus I I
No. % No. % LSIL I 3 4
HSIL 43 44 24 23* 10 II
More than one sexual partner 32 55.1 39 57.3 Total 44 44 30 28 14 II
Tobacco use 37 63.8 42 61.8
Ascus, atypical squamous cells of undetermined significance.
P, not significant. *P, not significant, compared to cesarean section.

7
248
made by cervical biopsy in the postpartum evaluation in
76% of 30 pregnant women with vaginal delivery and
in 78.6% of 14 women with cesarean section. CIN III
was diagnosed histologically in 36 (81.2%) of 44 prena-
tal biopsies. In postpartum biopsy, CIN III was diag-
nosed in 23 (76.7%) of 30 vaginal deliveries and 9
(64.3%) of 14 cesarean sections. The other 9 (17%) did
not have a follow-up after delivery; all of them had
HSIL according to cytology and biopsy during pregnan-
cy, but they decided to be treated at another hospital.
Postpartum treatment
Of the 44 patients submitted to a conservative treat-
ment with a cytological and colposcopy evaluation in
postpartum, 26 (59.1 %) were submitted to LEEP or
conization (Table 4), 6 (13.6%) had a normal postpar-
tum cytology and biopsy, 2 (4.6%) were submitted to
cryocauterium for CIN I, and 10 (22.7%) did not return
during the pregnant puerperal period for treatment.
Of these last 10 cases, 6 (60%) did not return to our
service for treatment. Two (20%) patients returned re-
spectively 4 and 5 years later after delivery and present-
ed CIN III in the current biopsy; conization and LEEP
were performed, respectively, and a micro-carcinoma
was diagnosed. Two (20%) patients returned 3 years lat-
er after delivery: 1 had another pregnancy and cytology
and colposcopic evaluation were normal, and the other
presented CIN III in biopsy but she refused treatment.
No case of invasive carcinoma was found. Patient fol-
low-up with complete evaluation in postpartum ranged
from 1 to 12 years (4.4 ± 4.3).
In the control group, of the 68 patients, 31 (45.6%)
were submitted to LEEP, 32 (47.1%) to conization, and
5 (7.3%) patients were treated in another hospital. Of 63
cone biopsies or LEEP specimens, CIN III was present
in 51 (80.9%) cases, CIN II in 1 (1.6%) case, and CIN I
in 3 (4.8%) cases; 3 (4.8%) cases of invasive carcinoma
were found, and neoplasia was not diagnosed in 5
(7.9%) cases. Adenocarcinoma in situ was present in 2
(3.2%) of 63 cases (P = not significant, Fisher's test,
compared to the gestational group).
Discussion
Our results did not show any statistically significant
difference in relation to the control group in mean age,
parity, age of first intercourse, number of sexual part-
ners during the last year before diagnosis, and tobacco
Table 4 - Distribution of 26 pregnant women submitted to treatment in the puerperal period
LEEP
Postpartum biopsy CIN III CINII CINI
CIN III 10
CINII
CINI
*Two (10%) cases of adenocarcinoma in situ were diagnosed concomitantly with CIN III (n = 20).
EFC MURTA, FHC DE SOUZA, MAH DE SOUZA, SJ ADAD
use. These results suggested that HSIL presented the
same epidemiological factors in pregnant and non-preg-
nant women. Mean age, parity, and tobacco use were
similar to those reported by other authors".
Cervical cancer and CIN in pregnant women have
been reported to have the same frequency as in non-
pregnant wornen-i. During pregnancy, approximately
14% of all cervical abnormalities are classified' as
HSIL. Pregnancy is not a risk factor for the develop-
ment of CIN 23, and the rate of CIN becoming invasive
cancer during gestation is 10w8 ,l3 . Nevertheless, in this
period, invasive disease was excluded if a conservative
management was established-".
Penna et at. 25 proposed that laser conization can be
carried out in the sixteenth week of gestation without
major complications. In contrast, some authors-r" have
stated that residual disease in pregnancy is more com-
mon because the excision cannot be as wide and deep
as necessary due to the risk of complications.
We demonstrated that ectopia was marginally signifi-
cant and more frequent in pregnant women. This was
expected because ectopia is more frequent in gestation
because of hormonal modifications'. This is an impor-
tant point, because the conservative management of
HSIL is more acceptable if colposcopy is satisfactory.
We believe that the absence of unsatisfactory col-
poscopy cases in both groups of our study is a casual
event. Unsatisfactory colposcopy has been reported in
0-12% of pregnant womenI3.27-30. Despite the high rates
of complications of conization during pregnancy, the
procedure is indicated in patients with an unsatisfactory
and a Papanicolaou smear suggestive of HSIL or of a
more severe lesion 27•28,
White epithelium was more frequent in pregnant
women with HSIL. The increased vascularity of the
cervix may exaggerate the acetic acid reaction, and mi-
nor changes can be misinterpreted as major changes 1.
This can explain our findings, even though all colpo-
scopic examinations were done by an experienced col-
poscopist, and it suggests that white epithelium is a
more frequent finding in pregnant women with HSIL.
Most HSIL diagnoses were made in the second and
third trimester of pregnancy. These results differ from
others authors who demonstrated that the diagnosis was
most common in the first trimester", The patients treat-
ed in our service have a low socioeconomic level, and
most pregnant women begin prenatal care after the first
trimester.
Conization
WithoutCIN CIN III CINII CINI WithoutCIN
10*
1
HSIL DURING PREGNANCY
No case of bleeding occurred in pregnant women
submitted to cervical biopsy during prepartum evalua-
tion. Literature data have demonstrated that cervical
biopsy done during pregnancy does not have any major
complications". We had one case of abortion but do not
believe it was due to biopsy complications because it
occurred some weeks later.
In 4 cases the women were not submitted to col-
poscopy or biopsy during the prenatal evaluation: 1 had
a normal cytology and colposcopy, and the other 3 had
an invasive carcinoma in the postpartum evaluation.
Benedet et al." found 5 of 9 women with invasive dis-
ease. They were not diagnosed until postpartum. Sood
et al. 32 compared the prognosis of 66 women with cer-
vical cancer, diagnosed during pregnancy, with the
prognosis of 27 women with cervical cancer, diagnosed
within 6 months of delivery and also analyzed the effect
of delivery route on recurrence risk and prognosis.
These authors showed that vaginal delivery was the
most significant predictor of recurrence, and women di-
agnosed postpartum had a worse survival than those di-
agnosed during pregnancy. These findings supported
the liberal use of colposcopic directed biopsies during
pregnancy for diagnosis and excluded invasive disease.
In contrast, our data showed that the delivery route did
not influence the prognosis of those patients with HSIL
diagnosis who had cytological and colposcopic evalua-
tion during pregnancy and after delivery. No invasive
disease was found in our patients after treatment during
a follow-up of 4.4 ± 4.3 years.
It has been postulated that spontaneous regression of
HSIL occurs due to trauma at delivery or changes in the
maternal immune status after pregnancy". Our results
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