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Luís Carlos Machado Junior Ana Sílvia Whitaker Dalmaso Heráclito Barbosa de Carvalho
Evidence for beneﬁts 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 beneﬁts from treating cervical ectopy. METHODS: The following databases were reviewed: 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 immunodeﬁciency virus infection; 4) there is probably an association 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 protection 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 attributed 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 occurrence of single-layered secreting columnar epithelium (which usually covers the cervical canal, i.e. the endocervix), beyond the external cervical oriﬁce. Thus, the multilayered squamous epithelium typically found in the vagina and exocervix are replaced.1-3 This condition has many designations in medical terminology: ectropion, erythroplakia, macula rubra and erosion.1,2,4,5 Not all factors involved in the pathogenesis 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 pregnancy2 and also among users of estrogen-based contraceptives.6-11 The rare examinations on newborns that have been reported show high prevalence, probably secondary 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 established. 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 stratiﬁed 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 condition 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 squamous 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 spontaneous 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 variants, is the treatment most often used. Patients are treated on an outpatient basis. The efﬁcacy 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 susceptible to carcinogens. Precancerous lesions often develop at the squamous-columnar junction, i.e. the area of transition between glandular and stratiﬁed 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
Sao Paulo Med J. 2008;126(2):132-9.
Other symptoms are also sometimes attributed to ectopy. were consulted to ascertain whether they knew of any evidence in the literature regarding the beneﬁts from treatment. The protocol for this study was approved by the Ethics Committee of Hospital das Clínicas. keywords used and search database Database searched Medline Keywords used NLM ‘Cervix diseases (MeSH) erosion’ NLM ‘Cervix erosion (MeSH)’ NLM ‘Cervix erosion’ NLM ‘(Pubmed) ectopy’ NLM ‘Cervix diseases (MeSH) ectopy’ Bireme Embase Lilacs ‘Diseases of uterine cervix’ ‘Cervix erosion’ ‘Uterine cervix erosion’ ‘Uterine cervix disease’ Ectropion Ectopy Cauterization Diseases of uterine cervix Cochrane Library (in controlled trials): Total ‘Ectopy and cervical’ ‘Ectropion and cervical’ ‘Erosion and cervical’ Total references 423 381 94 71 19 1541 6 11 128 2 4 11 198 4 5 19 2917 Total selected articles 9 2 3 17 1 12 0 1 0 0 0 1 0 1 0 0 47 Medline = Medical Literature Analysis and Retrieval System Online.18 which may cause discomfort to women. Distribution of the articles selected. Table 2. Table 1.23 Rocha-Zavaleta et al. this would entail the utilization of substantial physical and human resources. whose work has been focused on conditions of the lower genital tract and colposcopy.917 articles were found. METHODS This study consisted of a literature review including searches in the Medical Literature Analysis and Retrieval System Online (Medline).20 did not address the issue of treatment. RESULTS FROM THE LITERATURE REVIEW Specialized books Cartier and Cartier1 stated that ectopy is a physiological phenomenon and thus should not be treated. it was selected for analysis of its full text. thereby making cervical cancer prevention more difﬁcult. The objective of this study was to assess. Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) and Cochrane Library databases up to July 2006. according to total number of references. the squamous-columnar junction is very often displaced up to the cervical canal. but they did not offer any arguments or references to support this.14 We believe this is a major issue because of the high prevalence of ectopy. When there was any chance that a study somehow addressed the issue of beneﬁts or indications for treatment.126(2):132-9. These studies are presented here. Lilacs = Literatura Latino-Americana e do Caribe em Ciências da Saúde.62 Moreira et al. even indirectly. through a comprehensive review of the literature. In summary. Piato19 and Pereyra et al.61 Vonka et al. .15. Selected studies Table 1 shows the results from the database searches. with treatment. Studies dealing with the question of the beneﬁts from routine treatment are rarely seen (Table 2). If it were decided to treat all women with ectopy. above all. Singer and Monaghan3.2. Pereyra and Guerra16 recommended treatment. even though the treatment is not complex. whether these beneﬁts are purely theoretical or are based on evidence from clinical and/or epidemiological studies.25 Pereyra and Guerra16 De Palo4 Madej et al. Bireme = Biblioteca Regional de Medicina. which could indirectly imply that there are occasional beneﬁts from treatment. the titles and abstracts of the studies were evaluated. the Excerpta Medica Database (Embase) database from 1994 to 1999. Faculdade de Medicina da Universidade de São Paulo (HCFMUSP).59 De Punzio et al. 2008. In addition. two professors of Gynecology at two different public universities in São Paulo. what the alleged indications for and beneﬁts from treating ectopy are and. Authors who made suggestions regarding treatment for ectopy Author Leppaluoto21 Donahue22 Kauraniemi et al. De Palo4 recommended treatment because “stratiﬁed epithelium is more physiological in the exocervix”. The book does not contain bibliographical references. Hence the need to evaluate whether intervention produces any real beneﬁt. Embase = Excerpta Medica Database. Most of these studies addressed the efﬁcacy of treatment approaches promoting ectopy regression.24 Cartier and Cartier1 De Luca Brunori et al. They also argued that.60 La Vecchia et al.46 Type of work Opinion article Opinion article Cross-sectional study Cross-sectional study Cross-sectional study Case-control study Opinion article Text in book Laboratory study Text in book Text in book Opinion article Cross-sectional study Year of publication 1974 1976 1978 1984 1984 1985 1990 1994 1994 1994 1996 1999 2004 Recommended treatment Yes No Yes No Yes No No No Yes Yes Yes No Yes Argument for treatment Prevention of cervical cancer Prevention of cervical cancer Prevention of cervical cancer Better immunity None Not clear Prevention of cervical cancer Sao Paulo Med J. like pelvic pain and postcoital bleeding. 2. and sometimes the physiological or histological features of this condition as well. Berek et al. The review of the databases included the following approach: any study with ectopy as a main or secondary subject was searched. Once found. His opinion was not supported by bibliographical references.133 mucus production. and specialized books and references in books and selected articles. as well as a larger number of other studies showing possible associations between ectopy and certain diseases or symptoms.
4. Among the 48 studies selected.27 Arya et al. In a cross-sectional study on 97 HIVpositive women.0004 0.001 0.95-3. symptoms of ectopy.126(2):132-9.39 studied the relationship between sexual activity and CMV infection.33 Louv et al. One of these was a reference in another study.18 found a higher frequency of HIV isolation from the cervix and vagina in the women with ectopy.001 RR = 1.30. human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN). given the association with oral contraceptive use.005 0.10 Handsﬁeld et al. schooling level and race.29. Out of these 48 studies. Cytomegalovirus Collier et al.8 Mallinson et al.9 1. This association remained in the multivariate analysis: OR = 5. List of studies selected according to the association between Chlamydia infection and ectopy Author Ripa et al. Based on this ﬁnding. in addition to these arguments.11 Jacobson et al. Plourde et al.98 X2 = 12. and also an association between ectopy and shorter time for seroconversion. A further two crosssectional studies36.7 OR = 2.5-16.01 0. HIV Moss et al. a score including ectopy.34 reported that there was no association between gonococcus and ectopy (Table 3). RR = relative risk.11. 2008.30 Paavonen et al.6 RR = 1. The two professors consulted said that they were unaware of any clinical evidence in the literature regarding beneﬁts from treatment. Authors’ opinions Leppaluoto was in favor of routine treatment. No association was found between HIV infection and ectopy. Ectopy was also assessed.34 Critchlow et al.78 OR = 3. Out of all of these women.9.4 OR = 1. He found an association between cervical CMV infection and ectopy that disappeared in multivariate analysis that included age. four are not discussed here because they present major methodological ﬂaws.01 0. Donahue22 and Madej et al.33.8.05 0. They found that the women with ectopy were at greater risk of being HIV-positive.43 conducted a cross-sectional study among 189 HIV-positive adolescents and 92 HIV-negative adolescents.31 Rahm et al. p = 0. human immunodeficiency virus (HIV). .7.28 Harrison et al.134 A set of 48 studies was selected to be presented. to assess the association between the risk of HIV infection and contraceptive methods. and that this risk was maintained in multivariate analysis: odds ratio (OR) = 5.5-3.23 believed that ectopy was a physiological phenomenon and should only be treated when symptomatic. 95% confidence interval (CI) = 1.49 X2 = 9.38 Stergachis et al. studied asymptomatic women with ectopy and obtained biopsy samples from areas of ectopy and stratiﬁed epithelium.40-2. in order to prevent cervical cancer. Clemetson et al.33 2-6.32 Chacko and Lovchik 29 Wood et al. p = 0. 95% CI = 1. Moscicki et al.9 0.36 Blythe et al. US = United States. †Multivariate analysis did not include ectopy individually but. 95% CI = 1. Copies of eight studies not available in Brazil were imported. Moreira et al.35 this association was maintained in multivariate analyses.34 X2 = 3.24 95% CI p-value 0. OR = odds ratio.7. 21 Laboratory study De Luca Brunori et al. four expressed the authors’ opinions. C2 = chi-squared.40 conducted a cross-sectional study among 70 couples in which the men were HIV-positive.9% were HIV-positive.14.37 showed that this association disappeared in the multivariate analysis and a cohort study38 found a strong tendency towards an association but did not reach signiﬁcance. They found an association between ectopy and risk of HIV infection: relative risk (RR) = 3.37 * Year 1978 1980 1980 1981 1982 1984 1984 1985 1986 1988 1989 1989 1990 1991 1993 1995 2000 Location Sweden England England England England US England US US US US Sweden Sweden Sweden US US US Study design Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Clinical trial Cross-sectional Cohort Cross-sectional Cross-sectional Cross-sectional Type of analysis Univariate Univariate Univariate Univariate Univariate Univariate Univariate Multivariate Multivariate Multivariate Univariate Multivariate Univariate Univariate Multivariate Multivariate Multivariate Association Yes Yes* Yes Yes Yes* Yes Yes Yes† No Yes Yes Yes Yes No Yes Yes No MA X2 = 9. and cervical cancer and protection against this cancer by cauterization.7 Tait et al.11.007.24. they proposed that treatment should be undertaken routinely.96 X2 = 9. Factors Table 3.5 X2 = 24. No study regarded as relevant was left out of the analysis due to any language difﬁculty. Seven cross-sectional studies8. Sao Paulo Med J.7-14. In another four cross-sectional studies10.34 and in one clinical trial.26 Hobson et al.33.94 1.006. Clinical studies Chlamydia and gonococcus 25 Nine cross-sectional studies7. rather. They found lower cellular immune activity in areas of ectopy.35 Rahm et al.42 conducted a cross-sectional study comprising 4.9.97 0. cytomegalovirus (CMV). CI = conﬁdence interval.26-32 using univariate analysis reported an association between cervical Chlamydia infection and ectopy.404 women in family planning clinics.12-1.39 Association between infection intensity and ectopy. The clinical studies included the following topics: associations between ectopy and cervical infection due to Chlamydia trachomatis and Neisseria gonorrhoeae. one was a laboratory study and 43 were clinical studies. maintained that treatment did not prevent cervical cancer. Mati et al.2 – 12. 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. MA = measurement of association.41 conducted a cohort study on 134 HIV-negative women with genital ulcers.
their conclusion was based on a study with serious methodological ﬂaws and therefore it will not be discussed further here. statistical data not available). Juneja et al. 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. only the associations with mucus discharge and nocturia remained (p < 0. postcoital bleeding.55 95% CI 1. List of studies selected according to association between ectopy and HIV infection Author Moss et al. 14 conducted a crosssectional study correlating epidemiological features and symptoms with ectopy. ectopy was assessed using computer-processed images.9 OR = 1.04 (Table 4). In the multivariate analysis.5-15.98 p-value 0.99-4. parity.007 0. types) was greater than the expected rate for this population. 95% CI = 0.45-12. the association with ectopy was maintained. contraceptive method and evaluating physician. nocturia.498 women who had sought out a family planning center. At the time of data collection.9 1. was considered to be the deﬁnition of cancer.98.9 0.1 0. fungi.41 Mati et al. Moscicki et al. which. They studied 1.135 associated with their HIV status.50 conducted a case-control study comprising 75 adolescents with CIN and 75 controls.5-16. . Cervical cancer (Table 5) Goldacre et al.46 found a higher general HPV rate and also a higher rate of HPV 16 in women with ectopy. The Jiangxi Cooperative Group of Cervical Cancer52 conducted a case-control study in China. There was no association between ectopy and fungal. No differences were seen in the bacte- Simm and Doltaniak51 suggested that there was an association between ectopy and cervical cancer. The authors found an association between CIN and the intensity of metaplasia (which is related to ectopy). such as vaginal discharge. along Table 4. They were followed up at three to six-month intervals with colposcopy.06. 55 organized a cohort consisting of 1. painful intercourse. However. OR = odds ratio.7-2. Sarkar and Steele49 conducted a study on 100 women who had been referred to a clinic for ectopy treatment. CI = conﬁdence interval. Associations between 39 variables and cancer occurrence were assessed.4%) had cytological ﬁndings suggestive of invasive cancer.3-6. They suggested that the greater oncogenicity in this group could be due to higher afﬁnity to metaplastic epithelium in young women. 95% CI = 1. in 1980. dysuria. Thirty-six variables were investigated through direct interview. Ectopy was measured through computerized analysis.40 Clemetson et al. An association between ectopy and HPV (OR = 2.48 conducted a case-control study on 18 adolescents with CIN and 204 44 controls. Tests for pathogenic microorganisms of the cervix and vagina were also conducted: Trichomonas vaginalis. The cervix was classiﬁed as normal or presenting ectopic bleeding upon touch. and biopsy if necessary. conducted a cross-sectional study among 210 women to identify factors associated with inﬂammatory cytological conditions.005) was found.107 women with cytological ﬁndings suggestive of CIN. In the multivariate analysis.45 conducted a crosssectional 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.31-0. including ectopic bleeding upon touch. A total of 250 women (0. Castle et al. They studied 67. CIN was found in 19 patients. p = 0.3 OR = 0. for the purposes of that study.27.04 Moscicki et al. In a cross-sectional study. They also found an association between infection in the oncogenic group and younger age. 42 18 Year 1991 1993 1994 1995 2001 Location Kenya Kenya Kenya Kenya US Study design Cross-sectional Cross-sectional Cohort Cross-sectional Cross-sectional Type of analysis Multivariate Multivariate Univariate Univariate Multivariate Association Yes Yes* Yes No Yes (negative) Measurement of association OR = 5 OR = 5 RR = 4.31-0.126(2):132-9. if needed. Ectopy was found in 550 women (36. immediately before CIN was diagnosed: OR = 3.02 – 0. including ectopy. to prevent cervical cancer. A signiﬁcant association between cancer and all variables was seen.82. Duttagupta et al. 95% CI = 1.06 0.7%).47. 95% CI = 0.47 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). which included mucus discharge.55. Symptoms rial ﬂora of the vagina. Among other variables. Plourde et al. Moscicki et al. The women were asked about symptoms that are attributed to ectopy. They studied 306 women with cervical cancer and 306 controls. They found an association with ectopy.000 women who underwent a cytology test.09. either for HPV in general (OR = 2. The univariate analysis showed a negative association between ectopy and HIV infection.05). in areas with high HPV prevalence. all women underwent an examination.43 * Association between ectopy and viral isolation from vaginal and cervical discharges among HIV-positive women. They proposed routine treatment for ectopy. Zhang and Xu53 conducted a case-control study comprising 125 cases of cervical cancer and 125 controls in China. p = 0. cervical biopsy prior to treatment. These were followed up for an average of 32 months. nocturia. RR = relative risk. which remained in the multivariate analysis: OR = 0. Ectopy was evaluated through clinical examination. The authors considered that this CIN prevalence (both the high and low-grade. the association was not signiﬁcant. and pollakiuria. A signiﬁcantly higher rate of ectopy was found in women with the non-oncogenic group than in the other group (control group). and gonococcus and the bacterial ﬂora of the vagina.45). vulvar pruritus. He found a much higher frequency of HPV in biopsies from women with ectopy (all the participants underwent biopsy. and ﬁve of them had high-grade lesions. All of these women had normal cervical cytology.88-133). However. They found an association between these variables (RR = 4.7 1. Rocha-Zavaleta et al. “suspicious appearance” or “unhealthy” appearance.7-14.33) or for HPV 16 (OR = 6. Sao Paulo Med J.54 conducted a cross-sectional study to identify variables that were associated with cervical cancer. Murthy et al. were studied. among others. low back pain. All underwent colposcopy and. US = United States. 2008. Trichomonas vaginalis or gonococcal infection. HPV and CIN Toon et al. 95% CI = 0.
DISCUSSION OF THE STUDIES As mentioned earlier.94 Conﬁdence intervals and p-values not made available by the authors. In the Cochrane Library’s review. List of studies selected according to the association between cervical cancer and cauterization of ectopy Author Kauraniemi et al.62 * Year 1978 1984 1984 1985 Location Finland Czechoslovakia Italy Italy Type of analysis Univariate Univariate Univariate Multivariate Protection Yes Yes No No Measurement of protection* RR = 0. They compared the prevalence of preneoplastic and neoplastic lesions with histories of cauterization at any time and due to any indication. They found a protective effect for history of cauterization: 24.62) cited the aforementioned studies of Peyton et al.22-0. in situ carcinoma. Table 5. during interactions with teachers. beliefs and motivations. Within the same stratum of cytological tests. After stratiﬁcation by marital status. Two case-control studies were conducted simultaneously.832 women who underwent cervical cancer screening with cytological tests. physicians tend to recognize knowledge acquired both at medical school. Sao Paulo Med J.83 and was no longer signiﬁcant (95% CI = 0. although they did not address the main concern of the present study. In the multivariate analysis. They concluded that ectopy should be cauterized to prevent cervical cancer. Cancer prevention using cauterization Kanka et al. even though treatment for ectopy is a very common intervention. In their ﬁrst study.7% of those with CIN III and 9. Studies that evaluated the association between ectopy and cervical cancer Author Jiangxi Group52 Murthy et al. The second study had the same format as the ﬁrst one.64 and based on the physician’s performance.59 conducted a crosssectional population-based study among 429.55 Zhang and Xu53 Juneja et al.61 La Vecchia et al. adjusting for cauterization did not change the relative risk. education. After adjusting for the number of cervical cytological tests (none. except that the cases were women with CIN. only the association with age at marriage was maintained (p = 0. La Vecchia et al. and invasive carcinoma. differently from those other studies. 0. Over the course of 78 months of follow-up. Kauraniemi et al.54 Type of Study Case-control Cohort Case-control Case-control Year of publication 1986 1990 1990 1993 Association Yes No Yes Yes Table 6.4% of the women with cervical intraepithelial neoplasia grade I (CIN I).59 and Vonka et al. The lack of correlation between scientiﬁc evidence for beneﬁts and the widely practiced treatments makes it clear that. on invasive carcinoma. it was found that the RR increased to 0. for example.56. 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 life63.82. the same sequence of results was found. age at ﬁrst sexual intercourse and use of oral contraceptives. 95% CI = 0. parity.58. there were several articles that. They correlated histories of cauterization due to any indication at any time with the detection of malignant or premalignant histological lesions.61 conducted a cross-sectional study among 2.683 women to identify risk factors for CIN.94. 2008. The large number of articles dealing exclusively with treatment approaches corroborates this statement.9% of those with CIN II. it reached as high as 0. in the medical ﬁeld. However. They found a negative association between cauterization and neoplastic and preneoplastic cervical lesions. In the second study. The physician is not only a knowledge holder but also an individual who possesses values. 0. Herpes simplex I and II status and ectopy. After stratiﬁcation by age. which included age. and in their clinical experience. or two or more). and thus they will not be discussed further here.58 conducted studies to investigate cancer prevention using cauterization. 0. number of sexual partners. Kauraniemi et al. 6. Physicians make therapeutic decisions based on a set of sources.126(2):132-9.72).60 conducted a cross-section study among 10. The relative risks were: low-grade dysplasia.136 with cytological tests. one.23. 0. high-grade dysplasia. the clinical management methods are not only supported by recent scientiﬁc knowledge. in autonomous practice. the univariate analysis showed an apparent protective effect among cauterized women: RR = 0. the association disappeared for single women.5% of those with in situ carcinoma (p < 0. In the ﬁrst study.05). among women with CIN. . the cases were 191 women with invasive cervical cancer and there were 191 controls. parity. as seen in the present study.42.60 as major references on this issue. Thus. 8. RR = relative risk. They stated that. De Punzio et al.15 RR = 0.6% of the controls had cauterization versus 13.02). 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. In the multivariate analysis. with varying levels of patient involvement.40-1. Associations between progress to in situ carcinoma and the following variables were studied: age (35 years or over). only the efﬁcacy of treatments for ectopy regression was discussed. 75 women progressed to in situ carcinoma.24.65 If. They found no association. up-to-date scientiﬁc knowledge is paramount. Bouda and Dohnal57 and Peyton et al. the association remained. They concluded that cauterization protected against cervical cancer and noted that this protection might be greater than the protection resulting from mass screening programs.001 women in a private clinic for cervical cancer prevention. fetal losses. these studies presented methodological ﬂaws that made them inconsistent. their study showed evidence against the protective effect of cauterization for cervical cancer (Table 6). use or nonuse of contraception. suggested associations between ectopy and certain diseases or symptoms. These will be discussed now. These authors (La Vecchia et al.60 De Punzio et al. on the one hand. 62 conducted a casecontrol study with the speciﬁc objective of assessing whether electrocoagulation of ectopy protected against cervical cancer. few studies have been conducted to evaluate the benefits from routine treatment for ectopy.15.40. Vonka et al.59 Vonka et al. No association with ectopy was found.
such that ectopy favors infection.2%. it would never provide full protection. In the studies by Mati et al. For example. all the participants underwent colposcopy.40. it can be said that the ultimate argument in support of carrying out interventions to treat ectopy would be if it prevented cervical cancer. particular situations could be envisaged in which treatment would be justiﬁable. none of them even mentioned treatment for ectopy. The alleged beneﬁts in these speciﬁc situations are. 14 found an association (ﬁve also in multivariate analysis) and only three did not show it. However.14 showed that more symptoms are attributed to ectopy than are actually caused by it. when exposed to HIV. These authors did not ﬁnd any association between ectopy and progression to in situ carcinoma. the infection prevalence ranges from 3.17 Supposing these hypotheses to be true. which is the best approach for diagnosing ectopy.36 It can be concluded these conditions are not associated. it can be assumed that treatment for ectopy could reduce the risk of Chlamydia infection. which can be clinically mistaken for incipient cancer. 2008.54. the former rate is probably closer to that of the general population. In both studies. they probably comprised a group with higher exposure to sexually transmitted diseases and therefore to HIV.55.7% to 35%. In the study by Plourde et al. the study by Rahm et al. 95% CI = 0. Based on the Chlamydia studies reviewed here.50 The study by Sarkar and Steele49 suggested that there was an association between CIN and ectopy. there could be speciﬁc situations in which such interventions would be effective. and both studies by Moscicki et al. since they are on average younger and have lower sexual exposure. they could be considered to present ectopy (erosion).50 showed an association between these conditions. the studies presented here showed contradictory results. even with regard to fatal conditions. However. It would be an extensive therapeutic intervention of low efﬁcacy. Cervical cancer is a severe disease that is usually fatal when not treated in a timely manner. HIV associated with age and sexual exposure. for example. even when oncogenic virus subtypes are involved.33).24 Ectopy is. HPV and CIN A similar discussion holds for HIV infection. One likely explanation for these inconsistencies is that. since it was estimated in a primary care service. Among these three. however. the women with ectopy were drawn from the general population and thus were less likely to be exposed to HIV. all the women were exposed to an HIV-positive partner and. assuming that this population has higher susceptibility.33.42 and Moscicki et al. bias is even more likely.126(2):132-9. in theory. Cervical cancer It is accepted that ectopy should be treated when there are symptoms attributable to this condition that cause discomfort. There would be no sense.95-3. given the afﬁnity of Chlamydia for glandular epithelium. It can be assumed that women with ectopy are likely to be susceptible to HIV infection. it would be pointless to treat all women with ectopy to reduce this risk. and that ectopy favors the occurrence of these two conditions (a more likely scenario) rather than these conditions favoring the occurrence of ectopy. for example. Nonetheless. . It can also be assumed that a cause-effect relationship is likely. women with ectopy are at higher risk of infection. Based on these studies. CIN and HPV do not have a direct relationship with cervical cancer. However.17 Since the prevalence of ectopy is high. only theoretically inferred on the basis of the present review. it is very likely that well-established cancer was misdiagnosed as “ectopic bleeding upon touch”. its treatment would be an intervention of little beneﬁt. however. cases of HIV-negative women with HIV-positive partners. Sao Paulo Med J.30. Even if it were believed that treatment provided some protection. In the same way as with Chlamydia infection. The cancer diagnosis was made based on cytological data collected during the same evaluation as when ectopy was detected. Their focus was basically on identifying risk markers for those infections. Both of the case-control studies that investigated this issue (Jiangxi Co-operative Group of Cervical Cancer52 and Zhang and Xu53) reported that such an association existed.137 Gonococcus None of the seven studies investigating associations between ectopy and gonococcal infection was able to conﬁrm such an association. the alleged risk factors were assessed through a questionnaire applied to women and it is possible that there may have been some classiﬁcation bias. In contrast.48. Goldacre et al. there are strategies for managing Chlamydia infection in the general population that are more effective.11.78. This issue will be further discussed below. 15% of the incidence rate expected for a speciﬁc population (taking the protection factor estimated in the study by Kauraniemi et al.45.41.11 In Brazilian studies. Three of them showed associations with oncogenic subtypes. given the large population to be treated. They have not been proven across the population.66-68 It should be underlined that most infected women are asymptomatic. Moreover.. inversely All four studies dealing with HPV infection and ectopy44. but had a small sample and was not statistically signiﬁcant (OR = 1.48. In the study by Juneja et al. it would justify searching for and treating all detected cases of ectopy. hence the lack of association or negative association found. Chlamydia An association between Chlamydia infection and ectopy can be assumed to be very likely.60 showed an association between these conditions.11 Women with ectopy would thus comprise a group at lower risk of HIV exposure. When cancer patients are clinically examined before their cancer has been diagnosed. On the other hand. ectopy should be taken to be a risk factor for cervical cancer. since all the women had genital ulcers.43. be the most important argument in favor of routine treatment. Out of the 17 studies investigating this.38 showed a higher frequency of infection among women with ectopy. probably due to lower immune competence of their glandular epithelium. In the study by Moss et al. among the studies reviewed that dealt with the issues of HIV and Chlamydia.14. women with ectopy were more infected. and represent a problem only in that they may be possible carriers of infection. If this protection actually exists. In this case. Three studies dealing with associations between ectopy and CIN were reviewed. however. however. in the cohort studied by Murthy et al. the seven studies discussed above do not provide evidence for such an association. If it is assumed The existence of an association between ectopy and cervical cancer would.59) would have a great impact on the mortality and morbidity caused by this disease.8. consequently. for instance.2 An intervention leading to a reduction of.29.59. in cases of women with high exposure to sexually transmitted diseases and some difﬁculty in getting their partners to use condoms regularly. the infection rates have ranged from 4% to 11. in treating all women with ectopy with this purpose. Symptomatic ectopy that there is an association between ectopy and both HPV and CIN.
Am J Obstet Gynecol. the history of cauterization did not change the risk of cervical cancer.73(6):836-40. Cuello inﬂamatorio. is a confounder for cervical cytological ﬁndings. 29. smoking. 2. Eur J Cancer Prev. 1984. JAMA. Eschenbach DA. 3a ed. However. 1981. 1999. et al.39(7):568-73. 10. J Am Coll Health Assoc. Meaning of the word erosion.91(12):1171-6. 48.62 was speciﬁcally designed to explore this issue and showed that treatment for ectopy. Coupez F. 2008. 1974. Chlamydia trachomatis infection in sexually active adolescents: prevalence and risk factors.112(6):1000-4. Gynecol Oncol. Jeronimo J. Although three earlier studies had demonstrated apparent protection. 1991. Sharp DS. Br J Vener Dis. 13. Terruhn V. J Pediatr. Maggwa BN. Zenilman J. Colposcopia e patologia do trato genital inferior. it can be said that the current evidence does not support the hypothesis that treatment for ectopy provides protection against cervical cancer. sexual behavior. D’Costa L. J Infect Dis. 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Determinants of cervical ectopia and of cervicitis: age. Rivoire WA. 3 ed.24(3):167-8. Historical and clinical factors associated with Chlamydia trachomatis genitourinary infection in female adolescents.1(6115):748-50. Mardh PA. Stamm WE.52(6):698-702. Costin M. Clin Exp Obstet Gynecol. Gnarpe H. In: Carrera JM. Therefore. Vermund SH.183(6): 865-70. Rocha-Zavaleta L. 9.138 Cancer prevention using cauterization The studies by Kauraniemi et al. Cancer. Association of cervical ectopy with heterosexual transmission of human immunodeﬁciency virus: results of a study of couples in Nairobi.66(2):1218-24. Jasman LL. Pereyra E. São Paulo: Artes Médica. Kanowitz S. 44.115(3):487-93. 41. 24. 1989. São Paulo: Roca. CONCLUSION The present study allows the following conclusions: • No data in the medical literature was found supporting routine treatment for ectopy. Factors related to genital chlamydial infection: a prospective study.59 and Vonka et al. 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[STD screening in a public family planning clinic in Brazil]. de centros de saúde de São Paulo. Literatura Latino-Americane e do Caribe em Ciências da Saúde (Lilacs). 2007 Last received: March 7. 3) existe associação com mucorréia e nictúria. Ferraz do Lago R.33(1):49-60. Nuzzi FM. 1990. Brazil. 65. Jiangxi Co-operative Group of Cervical Cancer].5(2):131-4. [The signiﬁcance of electrodiathermocogulation in the prevention of cervix cancer]. Excerpta Medica Database (Embase). Franceschi S. Castro S. Cristofoletti ML. 1993. MD.61(5):732-6. MSc. Subrt I. Is electrodiathermy coagulation (EDC) of cervical ectropion effective in the prevention of cervical carcinoma? Eur J Gynaecol Oncol. Rev Bras Ginecol Obstet. Contraception. 64. Schraiber LB. Gritti P. Am J Obstet Gynecol. 1968. Teti G. The cytologic progression from benign to malignant changes in a cervical erosion. Biblioteca Cochrane e seis livros especializados. Epidemiological characteristics. Int J Cancer. 1993. Sources of funding: None Conﬂict of interest: None Date of ﬁrst submission: April 9. Faúndes A. Neoplasia do colo do útero. 1978. Neoplasma. et al. Br J Cancer. Faculdade de Medicina da Universidade de São Paulo (FMUSP). Faculdade de Medicina da Universidade de São Paulo (FMUSP). 2008 AUTHOR INFORMATION Luís Carlos Machado Junior.169(3):289-96. (+55 11) 3726-8452 — Fax. 2003. Zhonghua Zhong Liu Za Zhi. Vecoli LE. São Paulo: Hucitec. Place where the paper was presented: Master’s degree defense by Luis Carlos Machado Junior. Hardy E. 53.24(2):101-6. Sehgal A. MD. 63. PhD. Faculdade de Medicina da Universidade de São Paulo (FMUSP). Jelínek J. 1985.131(5):533-8. Murthy NS. Brazil. Decarli A. Sao Paulo Med J. Zhang GN. 58. São Paulo: Hucitec. Faúndes D. Ana Sílvia Whitaker Dalmaso. Telles E. MD. Simm S. 59. 56. Peyton FW. Räsänen-Virtanen U. Follow-up of users of intrauterine device with and without bacterial vaginosis and other cevicovaginal infections. Selective cervical cytology screening: discriminant analysis approach. Kanka J. 62. 2008 Accepted: March 7. [Epidemiologic factors in cervical cancer--investigation on 306 pairs of partners. 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. PALVRAS-CHAVE: Erosão cervical uterina. 1984. [On the problem of cancer prophylaxis by electrocoagulation in cervical erosion and in the changing zone]. Fasoli M. MÉTODOS: Pesquisa nas bases Medical Literature Analysis and Retrieval Sysem Online (Medline). Department of Preventive Medicine. Pavnica P. Codes JS. São Paulo. et al. 2008. São Paulo. 1990. pelo vírus HPV e maior risco de soroconversão para HIV.131(4):374-80. Gynecologist. 1984. Long-term study from a private gynecologic practice. Shukla DK. Centro de Saúde Escola Samuel Barnsley Pessoa. 54.58(2):105-9. Estruturação e transformação da prática médica: estudo de algumas características do modelo de trabalho na segunda metade do século XIX e início do século XX. Este estudo se propõe a realizar revisão da literatura buscando evidências de benefícios conseqüentes ao tratamento da ectopia. 1965. Kanka J. Electrocoagulation and the risk of cervical neoplasia. Centro de Saúde Escola Samuel Barnsley Pessoa.66(5):703-7. Stolz J. São Paulo. Z Geburtshilfe Gynakol. May 18. I. Juneja A. Svoboda B. [dissertation]. Satyanarayana L. 2) O tratamento pode ser utilizado para tratar sintomas associados à ectopia. 1998. Xu AQ.8(6):444-6. São Paulo: Faculdade de Medicina da Universidade de São Paulo. Cervicite uterina. Gentile A. Camargo RP. Monteiro I. Tecnologia e organização social das práticas de saúde: características tecnológicas do processo de trabalho na rede estadual 67. Gynaecologia. 68. 1994.139 51. Risk of cervical cancer among an electrocoagulated population. 2) existe provavelmente associação entre ectopia e neoplasia intra-epitelial cervical. Geburtshilfe Frauenheilkd. 3) Seriam necessários novos estudos para testar a hipótese de proteção contra o câncer de colo proporcionada pelo tratamento. 66. Medical hygienist. Bahamondes L. Dalmaso ASW. Heráclito Barbosa de Carvalho. Peyton RR. Fiore N. Sharma S. Die Bedeutung der Elektrodiathermokoagulation in der Prävention des Zervixkrebses.490 — Butantã São Paulo (SP) — Brasil — CEP 05503-000 Tel. 1978. Faculdade de Medicina da Universidade de São Paulo (FMUSP). Gonçalves RBM. Address for correspondence: Luís Carlos Machado Junior Av. Professor. Simões JA. 1986. 2004. 55. Murthy NS. Doltoniak D. Das DK. 52.68(2):105-9. Risk factors related to biological behaviour of precancerous lesions of the uterine cervix. Neoplasia intra-epitelial cervical. 57. . Vital Brasil. Anderson VL. mas parece ainda haver uma forte tendência no sentido da intervenção (tratamento). 1966. 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. 2002. Dr.162(1):48-56. RESULTADOS: A revisão mostrou que: 1) existe provavelmente associação de ectopia com infecção cervical por Chlamydia trachomatis.40(6):401-4. Contraception. The importance of cauterization to maintain a healthy cervix. La Vecchia C. O médico e seu trabalho: limites da liberdade. Pomponi P. 1991. Roy M. 60. Dohnal V. et al.11(4):212-6. Brazil. PhD. Hakama M. 1.br Copyright © 2008. Am J Obstet Gynecol. Prospective study on the relationship between cervical neoplasia and herpes simplex type-2 virus. Vonka V.25(12):1186-94. Perrotti M. Melo NA. [Conditional logistic regression analysis and path analysis of risk factors of cervical cancer]. Bouda J. Cohen DA. 61. Doenças do colo do útero. Detecção de doenças sexualmente transmissíveis em clínica de planejamento familiar da rede pública no Brasil.126(2):132-9. De Punzio C. Obstet Gynecol. (+55 11) 3726-2912 E-mail: csesbp@usp. The risk of inadvertent intrauterine device insertion in women carriers of endocervical Chlamydia trachomatis. porém mais sintomas são atribuídos à ectopia do que se pôde conﬁrmar em um estudo controlado. CONCLUSÕES: 1) Não foram encontrados na literatura dados que justiﬁquem o tratamento rotineiro da ectopia. Zhonghua Liu Xing Bing Xue Za Zhi. Kauraniemi T.
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