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ABSTRACT
Sao Paulo Med J. 2008;126(2):132-9.
REVIEW ARTICLE
Luís Carlos Machado Junior
Ana Sílvia Whitaker Dalmaso
Heráclito Barbosa de Carvalho
Evidence for benefi ts from treating
cervical ectopy: literature review
Centro de Saúde Escola Samuel Barnsley Pessoa, Faculdade de Medicina
da Universidade de São Paulo (FMUSP), São Paulo, Brazil
CONTEXT AND PURPOSE: Uterine cervical ectopy
(cervical erosion) is today considered to be a
physiological condition, but there still seems to
be a strong tendency towards treating it. The
purpose of this study was to review the medical
literature for evidence regarding benefi ts from
treating cervical ectopy.
METHODS: The following databases were re-
viewed: Medical Literature Analysis and Retrieval
System Online (Medline), Excerpta Medica
Database (Embase), Literatura Latino-Americana
e do Caribe em Ciências da Saúde (Lilacs) and
Cochrane Library databases. In addition, six
medical textbooks were consulted.
RESULTS: The review showed that: 1) there is
probably an association between ectopy and
higher risk of Chlamydia trachomatis, human
papillomavirus and human immunodefi ciency
virus infection; 4) there is probably an associa-
tion between ectopy and cervical intraepithelial
neoplasia; 5) there is an association between
ectopy and mucous discharge and nocturia;
and 6) there is no evidence of an association
between ectopy and cervical cancer, or of pro-
tection against cervical cancer associated with
ectopy treatment.
CONCLUSIONS: 1) No data were found in the
medical literature to support routine treatment
for ectopy; 2) Treatment could be recommended
for symptom relief, but more symptoms are at-
tributed to ectopy than could be demonstrated
in a controlled study; 3) Further studies to test the
hypothesis of protection against cervical cancer
associated with treatment are necessary.
KEY WORDS: Uterine cervical erosion. Uterine
cervicitis. Cervical intraepithelial neoplasia.
Uterine cervical dysplasia. Uterine cervical
neoplasm.
IntroduCTION
Uterine cervical ectopy is the occur-
rence of single-layered secreting columnar
epithelium (which usually covers the cervical
canal, i.e. the endocervix), beyond the exter-
nal cervical orifi ce. Thus, the multilayered
squamous epithelium typically found in the
vagina and exocervix are replaced.
1-3
This
condition has many designations in medi-
cal terminology: ectropion, erythroplakia,
macula rubra and erosion.
1,2,4,5
Not all factors involved in the pathogen-
esis of cervical ectopy are known but there is
an association with the action of estrogen.
2,3,6
Ectopy is rare beyond the menopause and
frequent at reproductive ages. It has higher
prevalence during pregnancy
2
and also among
users of estrogen-based contraceptives.
6-11
The
rare examinations on newborns that have been
reported show high prevalence, probably sec-
ondary to estrogens of pregnancy.
12
There is
also, starting in puberty, a negative association
with age, even before the menopause. Some
studies demonstrated a negative association
with the number of years of sexual activity
and number of partners.
2,7
The natural history of ectopy is well es-
tablished. After its development, a process of
metaplasia occurs in the columnar epithelium,
known as squamous metaplasia.
1,3
All women
go through this process, which may take
months or years, and the exposed columnar
epithelium is partially or fully converted into
stratifi ed squamous epithelium. The resulting
area is known as the transformation zone.
1,3
The prevalence reported for ectopy ranges
from 17 to 50%.
13,14
Given that its course is
usually time-limited, the prevalence estimates
in a population will detect only the women
with ectopy at that time. In such populations,
some women will already have had this condi-
tion and others will develop it. It is likely that
most women, if not all, will have ectopy at
some point during their lifetimes.
4,6
Cervical ectopy and the associated squa-
mous metaplasia are now considered to be
physiological phenomena.
1,15
Nonetheless,
its management has historically consisted of
interventions with the purpose of inducing or
accelerating its regression. There seems to be
a current trend towards less intervention, but
it is still very common. Although the spon-
taneous process of metaplasia almost always
leads to reduction or elimination of ectopy,
this is a much slower process than the process
resulting from treatment. The treatments
currently available are electrocoagulation,
cryocauterization, laser cauterization and drug
treatment.
16
Cauterization, in its several vari-
ants, is the treatment most often used. Patients
are treated on an outpatient basis. The effi cacy
for cauterization is around 90%.
16
There are several lines of argument that
would support routine treatment for ectopy.
The most common ones are:
a) Protection against cervical cancer. This is
probably the argument most generally seen.
There is a relationship between squamous
metaplasia and induction of squamous
cell carcinoma of the cervix.
2,3,15
Cells
undergoing metaplasia are more suscep-
tible to carcinogens. Precancerous lesions
often develop at the squamous-columnar
junction, i.e. the area of transition between
glandular and stratifi ed epithelium, which
is the location where metaplasia is most
intense.
15
Thus, theoretically, if this process
could be made to occur over a shorter time
span and if, by reducing ectopy, metaplasia
would be less extensive, there would be a
lower risk of cancer.
b) Some sexually transmitted microorganisms
such as Chlamydia trachomatis and Neisseria
gonorrhoeae preferentially infect glandular
epithelium. Ectopy would, by exposing this
epithelium, favor infection.
15,17
c) Ectopy consists of secreting epithelium,
and it is thus associated with increased
133
Sao Paulo Med J. 2008;126(2):132-9.
mucus production,
2,18
which may cause
discomfort to women. Other symptoms
are also sometimes attributed to ectopy,
like pelvic pain and postcoital bleeding.
14
We believe this is a major issue because
of the high prevalence of ectopy. If it were
decided to treat all women with ectopy, this
would entail the utilization of substantial
physical and human resources, even though
the treatment is not complex. Hence the need
to evaluate whether intervention produces any
real benefit.
The objective of this study was to assess,
through a comprehensive review of the litera-
ture, what the alleged indications for and ben-
efits from treating ectopy are and, above all,
whether these benefits are purely theoretical
or are based on evidence from clinical and/or
epidemiological studies.
METHODS
This study consisted of a literature review
including searches in the Medical Literature
Analysis and Retrieval System Online (Med-
line), Literatura Latino-Americana e do Caribe
em Ciências da Saúde (Lilacs) and Cochrane
Library databases up to July 2006; the Ex-
cerpta Medica Database (Embase) database
from 1994 to 1999; and specialized books
and references in books and selected articles.
In addition, two professors of Gynecology at
two different public universities in São Paulo,
whose work has been focused on conditions
of the lower genital tract and colposcopy, were
consulted to ascertain whether they knew of
any evidence in the literature regarding the
benefits from treatment.
The review of the databases included the
following approach: any study with ectopy
as a main or secondary subject was searched.
Once found, the titles and abstracts of the
studies were evaluated. When there was any
chance that a study somehow addressed the
issue of benefits or indications for treatment,
even indirectly, it was selected for analysis of
its full text.
The protocol for this study was approved
by the Ethics Committee of Hospital das
Clínicas, Faculdade de Medicina da Univer-
sidade de São Paulo (HCFMUSP).
RESULTS FROM THE
LITERATURE REVIEW
Specialized books
Cartier and Cartier
1
stated that ectopy is
a physiological phenomenon and thus should
not be treated. They also argued that, with
treatment, the squamous-columnar junction
is very often displaced up to the cervical
canal, thereby making cervical cancer pre-
vention more difficult. The book does not
contain bibliographical references. De Palo
4
recommended treatment because “strati-
fied epithelium is more physiological in the
exocervix”. His opinion was not supported
by bibliographical references. Pereyra and
Guerra
16
recommended treatment, but they
did not offer any arguments or references to
support this.
Singer and Monaghan
3
, Berek et al.
15
,
Piato
19
and Pereyra et al.
20
did not address the
issue of treatment.
Selected studies
Table 1 shows the results from the da-
tabase searches. In summary, 2,917 articles
were found. Most of these studies addressed
the efficacy of treatment approaches promot-
ing ectopy regression, and sometimes the
physiological or histological features of this
condition as well. Studies dealing with the
question of the benefits from routine treat-
ment are rarely seen (Table 2). These studies
are presented here, as well as a larger number
of other studies showing possible associations
between ectopy and certain diseases or symp-
toms, which could indirectly imply that there
are occasional benefits from treatment.
Table 1. Distribution of the articles selected, according to total number of references,
keywords used and search database
Database searched Keywords used Total references
Total selected
articles
Medline
NLM ‘Cervix diseases (MeSH) erosion’ 423 9
NLM ‘Cervix erosion (MeSH)’ 381 2
NLM ‘Cervix erosion’ 94 3
NLM ‘(Pubmed) ectopy’ 71 17
NLM ‘Cervix diseases (MeSH) ectopy’ 19 1
Bireme
‘Diseases of uterine cervix’ 1541 12
‘Cervix erosion’ 6 0
Embase
‘Uterine cervix erosion’ 11 1
‘Uterine cervix disease’ 128 0
Lilacs
Ectropion 2 0
Ectopy 4 0
Cauterization 11 1
Diseases of uterine cervix 198 0
Cochrane Library
(in controlled trials):
‘Ectopy and cervical’ 4 1
‘Ectropion and cervical’ 5 0
‘Erosion and cervical’ 19 0
Total 2917 47
Medline = Medical Literature Analysis and Retrieval System Online; Bireme = Biblioteca Regional de Medicina;
Embase = Excerpta Medica Database; Lilacs = Literatura Latino-Americana e do Caribe em Ciências da Saúde.
Table 2. Authors who made suggestions regarding treatment for ectopy
Author Type of work
Year of
publication
Recommended
treatment
Argument for
treatment
Leppaluoto
21
Opinion article 1974 Yes Prevention of
cervical cancer
Donahue
22
Opinion article 1976 No -
Kauraniemi et al.
59
Cross-sectional study 1978 Yes Prevention of
cervical cancer
De Punzio et al.
61
Cross-sectional study 1984 No -
Vonka et al.
60
Cross-sectional study 1984 Yes Prevention of
cervical cancer
La Vecchia et al.
62
Case-control study 1985 No -
Moreira et al.
24
Opinion article 1990 No -
Cartier and Cartier
1
Text in book 1994 No -
De Luca Brunori et al.
25
Laboratory study 1994 Yes Better immunity
Pereyra and Guerra
16
Text in book 1994 Yes None
De Palo
4
Text in book 1996 Yes Not clear
Madej et al.
23
Opinion article 1999 No -
Rocha-Zavaleta et al.
46
Cross-sectional study 2004 Yes Prevention of
cervical cancer
134
Sao Paulo Med J. 2008;126(2):132-9.
A set of 48 studies was selected to be
presented. One of these was a reference in
another study. The two professors consulted
said that they were unaware of any clinical
evidence in the literature regarding benefits
from treatment. No study regarded as relevant
was left out of the analysis due to any language
difficulty. Copies of eight studies not available
in Brazil were imported.
Among the 48 studies selected, four
expressed the authors’ opinions, one was a
laboratory study and 43 were clinical studies.
The clinical studies included the following
topics: associations between ectopy and cer-
vical infection due to Chlamydia trachomatis
and Neisseria gonorrhoeae, cytomegalovirus
(CMV), human immunodeficiency virus
(HIV), human papillomavirus (HPV) and
cervical intraepithelial neoplasia (CIN);
symptoms of ectopy; and cervical cancer and
protection against this cancer by cauteriza-
tion. Out of these 48 studies, four are not
discussed here because they present major
methodological flaws.
Authors’ opinions
Leppaluoto
21
was in favor of routine treat-
ment, in order to prevent cervical cancer.
Donahue
22
and Madej et al.
23
believed that
ectopy was a physiological phenomenon and
should only be treated when symptomatic.
Moreira et al.
24
, in addition to these argu-
ments, maintained that treatment did not
prevent cervical cancer.
Laboratory study
De Luca Brunori et al.
25
studied asymp-
tomatic women with ectopy and obtained
biopsy samples from areas of ectopy and
stratified epithelium. They found lower cel-
lular immune activity in areas of ectopy. Based
on this finding, they proposed that treatment
should be undertaken routinely.
Clinical studies
Chlamydia
and
gonococcus
Nine cross-sectional studies
7,8,26-32
using uni-
variate analysis reported an association between
cervical Chlamydia infection and ectopy. In
another four cross-sectional studies
10,11,33,34
and in
one clinical trial,
35
this association was maintained
in multivariate analyses. A further two cross-
sectional studies
36,37
showed that this association
disappeared in the multivariate analysis and a
cohort study
38
found a strong tendency towards
an association but did not reach significance.
Seven cross-sectional studies
8,11,14,29,30,33,34
reported that there was no association between
gonococcus and ectopy (Table 3).
Cytomegalovirus
Collier et al.
39
studied the relationship
between sexual activity and CMV infection.
He found an association between cervical
CMV infection and ectopy that disappeared
in multivariate analysis that included age,
schooling level and race.
HIV
Moss et al.
40
conducted a cross-sectional
study among 70 couples in which the men
were HIV-positive. They found that the
women with ectopy were at greater risk of
being HIV-positive, and that this risk was
maintained in multivariate analysis: odds
ratio (OR) = 5; 95% confidence interval
(CI) = 1.7-14.7; p = 0.007.
In a cross-sectional study on 97 HIV-
positive women, Clemetson et al.
18
found a
higher frequency of HIV isolation from the
cervix and vagina in the women with ectopy.
This association remained in the multivari-
ate analysis: OR = 5; 95% CI = 1.5-16.9;
p = 0.006.
Plourde et al.
41
conducted a cohort study
on 134 HIV-negative women with genital
ulcers. The group was followed up monthly
for six months and infection with the HIV
virus during this period was correlated with the
women’s characteristics. They found an associa-
tion between ectopy and risk of HIV infection:
relative risk (RR) = 3.9; 95% CI = 1.2 – 12.7;
and also an association between ectopy and
shorter time for seroconversion.
Mati et al.
42
conducted a cross-sectional
study comprising 4,404 women in fam-
ily planning clinics, to assess the association
between the risk of HIV infection and con-
traceptive methods. Ectopy was also assessed,
given the association with oral contraceptive
use. Out of all of these women, 4.9% were
HIV-positive. No association was found be-
tween HIV infection and ectopy.
Moscicki et al.
43
conducted a cross-sec-
tional study among 189 HIV-positive adoles-
cents and 92 HIV-negative adolescents. Factors
Table 3. List of studies selected according to the association between Chlamydia infection and ectopy
Author Year Location Study design Type of analysis Association MA 95% CI p-value
Ripa et al.
26
1978 Sweden Cross-sectional Univariate Yes
Hobson et al.
7
1980 England Cross-sectional Univariate Yes
*
X
2
= 9.98 0.01
Tait et al.
27
1980 England Cross-sectional Univariate Yes X
2
= 12.5 0.0004
Arya et al.
8
1981 England Cross-sectional Univariate Yes X
2
= 24.34 0.001
Mallinson et al.
32
1982 England Cross-sectional Univariate Yes
*
X
2
= 3.96 0.05
Chacko and Lovchik
29
1984 US Cross-sectional Univariate Yes
Wood et al.
28
1984 England Cross-sectional Univariate Yes X
2
= 9.24 0.001
Harrison et al.
10
1985 US Cross-sectional Multivariate Yes
†
Handsfield et al.
36
1986 US Cross-sectional Multivariate No
Blythe et al.
33
1988 US Cross-sectional Multivariate Yes
Louv et al.
30
1989 US Cross-sectional Univariate Yes RR = 1.49 1.12-1.97 0.005
Paavonen et al.
35
1989 Sweden Clinical trial Multivariate Yes
Rahm et al.
31
1990 Sweden Cross-sectional Univariate Yes X
2
= 9.6 0.01
Rahm et al.
38
1991 Sweden Cohort Univariate No RR = 1.78 0.95-3.33
Stergachis et al.
34
1993 US Cross-sectional Multivariate Yes OR = 3.7 2-6.9
Critchlow et al.
11
1995 US Cross-sectional Multivariate Yes OR = 2.4 1.5-3.9
Jacobson et al.
37
2000 US Cross-sectional Multivariate No OR = 1.94 0.40-2.39
*
Association between infection intensity and ectopy;
†
Multivariate analysis did not include ectopy individually but, rather, a score including ectopy.
MA = measurement of association; CI = confidence interval; C2 = chi-squared; OR = odds ratio; RR = relative risk; US = United States.
135
Sao Paulo Med J. 2008;126(2):132-9.
associated with their HIV status, including
ectopy, were studied. Ectopy was measured
through computerized analysis. The univariate
analysis showed a negative association between
ectopy and HIV infection, which remained
in the multivariate analysis: OR = 0.55; 95%
CI = 0.31-0.98; p = 0.04 (Table 4).
HPV and CIN
Toon et al.
44
conducted a cross-sectional
study among 210 women to identify factors
associated with inflammatory cytological con-
ditions. He found a much higher frequency of
HPV in biopsies from women with ectopy (all
the participants underwent biopsy; statistical
data not available).
Duttagupta et al.
45
conducted a cross-
sectional study on 850 women to assess the
validity of detection of HPV subtypes 16 and
18 (which were considered to be oncogenic)
as an approach for cervical cancer screening.
An association between ectopy and HPV
(OR = 2.09; p = 0.005) was found.
In a cross-sectional study, Rocha-Zavaleta
et al.
46
found a higher general HPV rate and
also a higher rate of HPV 16 in women
with ectopy. However, the association was
not significant, either for HPV in general
(OR = 2.06; 95% CI = 0.99-4.33) or for HPV
16 (OR = 6.47; 95% CI = 0.88-133). They
proposed routine treatment for ectopy, in
areas with high HPV prevalence, to prevent
cervical cancer.
Castle et al.
47
studied the relationship
between ectopy and two different groups of
HPV: the alpha 9 group (mostly oncogenic)
and the alpha 3/alpha 15 group (mostly
non-oncogenic). A significantly higher rate
of ectopy was found in women with the
non-oncogenic group than in the other group
(control group). They also found an asso-
ciation between infection in the oncogenic
group and younger age. They suggested that
the greater oncogenicity in this group could
be due to higher affinity to metaplastic epi-
thelium in young women.
Moscicki et al.
48
conducted a case-control
study on 18 adolescents with CIN and 204
controls. Among other variables, ectopy was
assessed using computer-processed images.
They found an association between these vari-
ables (RR = 4.27; 95% CI = 1.45-12.45).
Sarkar and Steele
49
conducted a study
on 100 women who had been referred to
a clinic for ectopy treatment. All of these
women had normal cervical cytology. All
underwent colposcopy and, if needed, cervical
biopsy prior to treatment. CIN was found in
19 patients, and five of them had high-grade
lesions. The authors considered that this CIN
prevalence (both the high and low-grade,
types) was greater than the expected rate for
this population.
Moscicki et al.
50
conducted a case-control
study comprising 75 adolescents with CIN
and 75 controls. These were followed up for
an average of 32 months. The authors found
an association between CIN and the intensity
of metaplasia (which is related to ectopy),
immediately before CIN was diagnosed:
OR = 3; 95% CI = 1.3-6.82.
Symptoms
Goldacre et al.
14
conducted a cross-
sectional study correlating epidemiological
features and symptoms with ectopy. They
studied 1,498 women who had sought out a
family planning center. Ectopy was evaluated
through clinical examination. The women
were asked about symptoms that are attrib-
uted to ectopy, such as vaginal discharge,
vulvar pruritus, low back pain, postcoital
bleeding, painful intercourse, dysuria, noc-
turia, and pollakiuria. Tests for pathogenic
microorganisms of the cervix and vagina
were also conducted: Trichomonas vaginalis,
fungi, and gonococcus and the bacterial flora
of the vagina. The person who performed
the examination (for detecting ectopy) was
unaware of the subjects’ symptoms and the
person who evaluated the symptoms was
unaware of the existence of ectopy. Ectopy
was found in 550 women (36.7%). There was
no association between ectopy and fungal,
Trichomonas vaginalis or gonococcal infec-
tion. No differences were seen in the bacte-
rial flora of the vagina. In the multivariate
analysis, which included mucus discharge,
nocturia, parity, contraceptive method and
evaluating physician, only the associations
with mucus discharge and nocturia remained
(p < 0.05).
Cervical cancer (Table 5)
Simm and Doltaniak
51
suggested that
there was an association between ectopy and
cervical cancer. However, their conclusion
was based on a study with serious method-
ological flaws and therefore it will not be
discussed further here.
The Jiangxi Cooperative Group of
Cervical Cancer
52
conducted a case-control
study in China, in 1980. They studied 306
women with cervical cancer and 306 controls.
Thirty-six variables were investigated through
direct interview. They found an association
with ectopy.
Zhang and Xu
53
conducted a case-control
study comprising 125 cases of cervical cancer
and 125 controls in China. Associations
between 39 variables and cancer occurrence
were assessed. In the multivariate analysis,
the association with ectopy was maintained,
among others.
Juneja et al.
54
conducted a cross-sectional
study to identify variables that were associated
with cervical cancer. They studied 67,000
women who underwent a cytology test. At the
time of data collection, all women underwent
an examination. The cervix was classified as
normal or presenting ectopic bleeding upon
touch, “suspicious appearance” or “unhealthy”
appearance. A total of 250 women (0.4%)
had cytological findings suggestive of invasive
cancer, which, for the purposes of that study,
was considered to be the definition of cancer.
A significant association between cancer and
all variables was seen, including ectopic bleed-
ing upon touch.
Murthy et al.
55
organized a cohort
consisting of 1,107 women with cytological
findings suggestive of CIN. They were fol-
lowed up at three to six-month intervals with
colposcopy, and biopsy if necessary, along
Table 4. List of studies selected according to association between ectopy and HIV infection
Author Year Location Study design Type of analysis Association Measurement of association 95% CI p-value
Moss et al.
40
1991 Kenya Cross-sectional Multivariate Yes OR = 5 1.7-14.7 0.007
Clemetson et al.
18
1993 Kenya Cross-sectional Multivariate Yes* OR = 5 1.5-16.9 0.06
Plourde et al.
41
1994 Kenya Cohort Univariate Yes RR = 4.9 1.5-15.9 0.02
Mati et al.
42
1995 Kenya Cross-sectional Univariate No OR = 1.3 0.7-2.1 –
Moscicki et al.
43
2001 US Cross-sectional Multivariate Yes (negative) OR = 0.55 0.31-0.98 0.04
*
Association between ectopy and viral isolation from vaginal and cervical discharges among HIV-positive women.
CI = confidence interval; OR = odds ratio; RR = relative risk; US = United States.
136
Sao Paulo Med J. 2008;126(2):132-9.
with cytological tests. Associations between
progress to in situ carcinoma and the follow-
ing variables were studied: age (35 years or
over), use or nonuse of contraception, parity,
fetal losses, Herpes simplex I and II status
and ectopy. Over the course of 78 months
of follow-up, 75 women progressed to in
situ carcinoma. In the multivariate analysis,
only the association with age at marriage was
maintained (p = 0.02). No association with
ectopy was found.
Cancer prevention using
cauterization
Kanka et al.
56
, Bouda and Dohnal
57
and
Peyton et al.
58
conducted studies to investigate
cancer prevention using cauterization. How-
ever, these studies presented methodological
flaws that made them inconsistent, and thus
they will not be discussed further here.
Kauraniemi et al.
59
conducted a cross-
sectional population-based study among
429,832 women who underwent cervical
cancer screening with cytological tests.
They correlated histories of cauterization
due to any indication at any time with the
detection of malignant or premalignant
histological lesions. They found a negative
association between cauterization and neo-
plastic and preneoplastic cervical lesions.
The relative risks were: low-grade dysplasia,
0.40; high-grade dysplasia, 0.24; in situ
carcinoma, 0.23; and invasive carcinoma,
0.15. After stratification by age, the associa-
tion remained. After stratification by marital
status, the association disappeared for single
women. They concluded that cauterization
protected against cervical cancer and noted
that this protection might be greater than
the protection resulting from mass screen-
ing programs.
Vonka et al.
60
conducted a cross-section
study among 10,683 women to identify risk
factors for CIN. They found a protective ef-
fect for history of cauterization: 24.6% of the
controls had cauterization versus 13.4% of the
women with cervical intraepithelial neoplasia
grade I (CIN I), 6.9% of those with CIN II,
8.7% of those with CIN III and 9.5% of
those with in situ carcinoma (p < 0.05). They
concluded that ectopy should be cauterized to
prevent cervical cancer.
De Punzio et al.
61
conducted a cross-sec-
tional study among 2,001 women in a private
clinic for cervical cancer prevention. They
compared the prevalence of preneoplastic and
neoplastic lesions with histories of cauteriza-
tion at any time and due to any indication.
They found no association.
La Vecchia et al.
62
conducted a case-
control study with the specific objective
of assessing whether electrocoagulation of
ectopy protected against cervical cancer.
Two case-control studies were conducted
simultaneously. In the first study, the cases
were 191 women with invasive cervical
cancer and there were 191 controls. The
second study had the same format as the
first one, except that the cases were women
with CIN.
In their first study, on invasive carci-
noma, the univariate analysis showed an
apparent protective effect among cauterized
women: RR = 0.42; 95% CI = 0.22-0.82.
After adjusting for the number of cervi-
cal cytological tests (none, one, or two or
more), it was found that the RR increased
to 0.83 and was no longer significant (95%
CI = 0.40-1.72). In the multivariate analy-
sis, which included age, education, parity,
number of sexual partners, age at first sexual
intercourse and use of oral contraceptives,
it reached as high as 0.94. Within the same
stratum of cytological tests, adjusting for
cauterization did not change the relative
risk. In the second study, among women
with CIN, the same sequence of results
was found.
These authors (La Vecchia et al.
62
) cited
the aforementioned studies of Peyton et
al.
58
, Kauraniemi et al.
59
and Vonka et al.
60
as major references on this issue. They stated
that, differently from those other studies,
their study showed evidence against the
protective effect of cauterization for cervical
cancer (Table 6).
DISCUSSION OF THE STUDIES
As mentioned earlier, few studies have
been conducted to evaluate the benefits
from routine treatment for ectopy. In the
Cochrane Library’s review, for example, only
the efficacy of treatments for ectopy regres-
sion was discussed.
The small number of studies reviewing
the validity of routine treatment indicates
that the medical scientific community has
not been greatly interested in answering
this question, even though treatment for
ectopy is a very common intervention. The
large number of articles dealing exclusively
with treatment approaches corroborates
this statement.
The lack of correlation between scientific
evidence for benefits and the widely practiced
treatments makes it clear that, in the medi-
cal field, the clinical management methods
are not only supported by recent scientific
knowledge. Some authors have pointed out
that Medicine has the characteristics of
a practice that is supported by scientific
knowledge but connected to other areas of
social life
63,64
and based on the physician’s
performance. The physician is not only a
knowledge holder but also an individual who
possesses values, beliefs and motivations.
65
If, on the one hand, up-to-date scien-
tific knowledge is paramount, as seen in the
present study, physicians tend to recognize
knowledge acquired both at medical school,
during interactions with teachers, and in
their clinical experience, in autonomous
practice. Physicians make therapeutic deci-
sions based on a set of sources, with varying
levels of patient involvement.
Thus, there were several articles that, al-
though they did not address the main concern
of the present study, suggested associations
between ectopy and certain diseases or symp-
toms. These will be discussed now.
Table 5. Studies that evaluated the association between ectopy and cervical cancer
Author Type of Study Year of publication Association
Jiangxi Group
52
Case-control 1986 Yes
Murthy et al.
55
Cohort 1990 No
Zhang and Xu
53
Case-control 1990 Yes
Juneja et al.
54
Case-control 1993 Yes
Table 6. List of studies selected according to the association between cervical cancer
and cauterization of ectopy
Author Year Location Type of analysis Protection
Measurement
of protection*
Kauraniemi et al.
59
1978 Finland Univariate Yes RR = 0.15
Vonka et al.
60
1984 Czechoslovakia Univariate Yes
De Punzio et al.
61
1984 Italy Univariate No
La Vecchia et al.
62
1985 Italy Multivariate No RR = 0.94
*
Confidence intervals and p-values not made available by the authors. RR = relative risk.
137
Sao Paulo Med J. 2008;126(2):132-9.
Gonococcus
None of the seven studies investigating
associations between ectopy and gonococcal
infection was able to confirm such an associa-
tion.
8,11,14,29,30,33,36
It can be concluded these
conditions are not associated.
Chlamydia
An association between Chlamydia infec-
tion and ectopy can be assumed to be very
likely. Out of the 17 studies investigating this,
14 found an association (five also in multivari-
ate analysis) and only three did not show it.
Among these three, the study by Rahm et
al.
38
showed a higher frequency of infection
among women with ectopy, but had a small
sample and was not statistically significant
(OR = 1.78; 95% CI = 0.95-3.33).
It can also be assumed that a cause-effect
relationship is likely, such that ectopy favors
infection, given the affinity of Chlamydia
for glandular epithelium.
17
Supposing these
hypotheses to be true, it can be assumed that
treatment for ectopy could reduce the risk of
Chlamydia infection.
There would be no sense, however, in
treating all women with ectopy with this
purpose. Based on the Chlamydia studies
reviewed here, the infection prevalence ranges
from 3.7% to 35%; the former rate is probably
closer to that of the general population, since
it was estimated in a primary care service.
11
In Brazilian studies, the infection rates have
ranged from 4% to 11.2%.
66-68
It should
be underlined that most infected women
are asymptomatic, and represent a problem
only in that they may be possible carriers of
infection.
17
Since the prevalence of ectopy is
high, its treatment would be an intervention
of little benefit, given the large population to
be treated. Moreover, there are strategies for
managing Chlamydia infection in the general
population that are more effective. None-
theless, there could be specific situations in
which such interventions would be effective,
for instance, in cases of women with high
exposure to sexually transmitted diseases and
some difficulty in getting their partners to use
condoms regularly.
HIV
A similar discussion holds for HIV infec-
tion. It can be assumed that women with
ectopy are likely to be susceptible to HIV
infection. However, the studies presented
here showed contradictory results. One likely
explanation for these inconsistencies is that,
when exposed to HIV, women with ectopy
are at higher risk of infection, probably due to
lower immune competence of their glandular
epithelium.
24
Ectopy is, however, inversely
associated with age and sexual exposure.
11
Women with ectopy would thus comprise a
group at lower risk of HIV exposure, since
they are on average younger and have lower
sexual exposure. In the study by Moss et al.
40
,
all the women were exposed to an HIV-posi-
tive partner and, consequently, women with
ectopy were more infected. In the studies by
Mati et al.
42
and Moscicki et al.
43
, the women
with ectopy were drawn from the general
population and thus were less likely to be
exposed to HIV, hence the lack of association
or negative association found. In the study by
Plourde et al.
41
, since all the women had geni-
tal ulcers, they probably comprised a group
with higher exposure to sexually transmitted
diseases and therefore to HIV.
On the other hand, assuming that this
population has higher susceptibility, it would
be pointless to treat all women with ectopy
to reduce this risk, even with regard to fatal
conditions. It would be an extensive thera-
peutic intervention of low efficacy. Even if it
were believed that treatment provided some
protection, it would never provide full protec-
tion. In the same way as with Chlamydia infec-
tion, particular situations could be envisaged
in which treatment would be justifiable, for
example, cases of HIV-negative women with
HIV-positive partners.
The alleged benefits in these specific
situations are, however, only theoretically
inferred on the basis of the present review.
They have not been proven across the
population. For example, among the stud-
ies reviewed that dealt with the issues of
HIV and Chlamydia, none of them even
mentioned treatment for ectopy. Their focus
was basically on identifying risk markers for
those infections.
Symptomatic ectopy
It is accepted that ectopy should be treated
when there are symptoms attributable to this
condition that cause discomfort. However,
Goldacre et al.
14
showed that more symptoms
are attributed to ectopy than are actually
caused by it.
HPV and CIN
All four studies dealing with HPV
infection and ectopy
44,45,59,60
showed an as-
sociation between these conditions. Three
of them showed associations with oncogenic
subtypes. Three studies dealing with asso-
ciations between ectopy and CIN were re-
viewed.
48,50
The study by Sarkar and Steele
49
suggested that there was an association
between CIN and ectopy, and both studies
by Moscicki et al.
48,50
showed an association
between these conditions. If it is assumed
that there is an association between ectopy
and both HPV and CIN, and that ectopy
favors the occurrence of these two condi-
tions (a more likely scenario) rather than
these conditions favoring the occurrence of
ectopy, ectopy should be taken to be a risk
factor for cervical cancer.
However, the seven studies discussed
above do not provide evidence for such an
association. CIN and HPV do not have a
direct relationship with cervical cancer, even
when oncogenic virus subtypes are involved.
Based on these studies, it can be said that the
ultimate argument in support of carrying out
interventions to treat ectopy would be if it
prevented cervical cancer. This issue will be
further discussed below.
Cervical cancer
The existence of an association between
ectopy and cervical cancer would, in theory,
be the most important argument in favor
of routine treatment. Cervical cancer is a
severe disease that is usually fatal when not
treated in a timely manner.
2
An interven-
tion leading to a reduction of, for example,
15% of the incidence rate expected for a
specific population (taking the protection
factor estimated in the study by Kaurani-
emi et al.,
59
) would have a great impact on
the mortality and morbidity caused by this
disease. If this protection actually exists, it
would justify searching for and treating all
detected cases of ectopy.
Both of the case-control studies that
investigated this issue (Jiangxi Co-opera-
tive Group of Cervical Cancer
52
and Zhang
and Xu
53
) reported that such an association
existed. In both studies, however, the al-
leged risk factors were assessed through a
questionnaire applied to women and it is
possible that there may have been some
classification bias. When cancer patients are
clinically examined before their cancer has
been diagnosed, they could be considered
to present ectopy (erosion), which can be
clinically mistaken for incipient cancer.
In the study by Juneja et al.
54
, bias is even
more likely. The cancer diagnosis was made
based on cytological data collected during the
same evaluation as when ectopy was detected.
In this case, it is very likely that well-estab-
lished cancer was misdiagnosed as “ectopic
bleeding upon touch”.
In contrast, in the cohort studied by
Murthy et al.
55
, all the participants underwent
colposcopy, which is the best approach for
diagnosing ectopy. These authors did not find
any association between ectopy and progres-
sion to in situ carcinoma.
138
Sao Paulo Med J. 2008;126(2):132-9.
Cancer prevention using
cauterization
The studies by Kauraniemi et al.
59
and Von-
ka et al.
60
suggested that cauterization would
have a protective effect, but not all possible
confounders were properly controlled for.
The most convincing study is certainly the
one by La Vecchia et al.
62
Based on arguments
developed in previous studies, they questioned
them using proper methodology. Although
three earlier studies had demonstrated ap-
parent protection, the study by La Vecchia et
al.
62
was specifically designed to explore this
issue and showed that treatment for ectopy, is
a confounder for cervical cytological findings.
The protection factor, which was of magni-
tude similar to what had been found by other
authors, disappeared after controlling for the
number of cytological tests. After stratifying
according to the number of cytological tests,
the history of cauterization did not change the
risk of cervical cancer.
Therefore, it can be said that the current
evidence does not support the hypothesis
that treatment for ectopy provides protection
against cervical cancer. It is remarkable that
the study by La Vecchia et al.
62
was published
as long ago as 1985. In the present review, no
studies of more recent date that retested this
hypothesis were found.
CONCLUSION
The present study allows the following
conclusions:
• No data in the medical literature was
found supporting routine treatment for
ectopy.
• Treatment can be used to relieve occa-
sional symptoms associated with ectopy.
However, more symptoms are attributed
to this condition than can be confirmed
in a controlled study.
• Further studies designed to test the hy-
pothesis that protection against cervical
cancer is provided by treatment for ectopy
are needed.
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AUTHOR INFORMATION
Luís Carlos Machado Junior, MD, MSc. Gynecologist, Centro
de Saúde Escola Samuel Barnsley Pessoa, Faculdade de
Medicina da Universidade de São Paulo (FMUSP), São
Paulo, Brazil.
Ana Sílvia Whitaker Dalmaso, MD, PhD. Medical hygienist,
Centro de Saúde Escola Samuel Barnsley Pessoa, Facul-
dade de Medicina da Universidade de São Paulo (FMUSP),
São Paulo, Brazil.
Heráclito Barbosa de Carvalho, MD, PhD. Professor, Depart-
ment of Preventive Medicine, Faculdade de Medicina da
Universidade de São Paulo (FMUSP), São Paulo, Brazil.
Place where the paper was presented: Master’s degree
defense by Luis Carlos Machado Junior, Faculdade de
Medicina da Universidade de São Paulo (FMUSP), May
18, 2004.
Address for correspondence:
Luís Carlos Machado Junior
Av. Dr. Vital Brasil, 1.490 — Butantã
São Paulo (SP) — Brasil — CEP 05503-000
Tel. (+55 11) 3726-8452 — Fax. (+55 11) 3726-2912
E-mail: csesbp@usp.br
Copyright © 2008, Associação Paulista de Medicina
RESUMO
Evidências de benefícios no tratamento de ectopia do colo do útero: revisão de literatura
CONTEXTO E OBJETIVO: A ectopia do colo do útero é hoje considerada um fenômeno fisiológico, mas parece
ainda haver uma forte tendência no sentido da intervenção (tratamento). Este estudo se propõe a realizar
revisão da literatura buscando evidências de benefícios conseqüentes ao tratamento da ectopia.
MÉTODOS: Pesquisa nas bases Medical Literature Analysis and Retrieval Sysem Online (Medline), Excerp-
ta Medica Database (Embase), Literatura Latino-Americane e do Caribe em Ciências da Saúde (Lilacs),
Biblioteca Cochrane e seis livros especializados.
RESULTADOS: A revisão mostrou que: 1) existe provavelmente associação de ectopia com infecção cervical
por Chlamydia trachomatis, pelo vírus HPV e maior risco de soroconversão para HIV; 2) existe provavel-
mente associação entre ectopia e neoplasia intra-epitelial cervical; 3) existe associação com mucorréia e
nictúria; 4) não existem evidências sobre associação entre ectopia e câncer de colo do útero nem sobre
proteção contra este câncer proporcionada pelo tratamento da ectopia.
CONCLUSÕES: 1) Não foram encontrados na literatura dados que justifiquem o tratamento rotineiro da
ectopia; 2) O tratamento pode ser utilizado para tratar sintomas associados à ectopia, porém mais sintomas
são atribuídos à ectopia do que se pôde confirmar em um estudo controlado; 3) Seriam necessários novos
estudos para testar a hipótese de proteção contra o câncer de colo proporcionada pelo tratamento.
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Sources of funding: None
Conflict of interest: None
Date of first submission: April 9, 2007
Last received: March 7, 2008
Accepted: March 7, 2008
