ORIGINAL STUDY
Increase in Cervical Adenocarcinoma Rate in Goiaˆnia, GO, Brazil Edesio Martins, MsHSc,* Maria Paula Curado, MD, PhD,*Þ Nilceana Maya Aires Freitas, MD, MsHSc,þ Jose´ Carlos de Oliveira, MD, PhD,* and Ruffo Freitas-Junior, MD, PhD§
Aim: To analyze the incidence and mortality trends of cervical adenocarcinoma in Goiaˆnia, Brazil. Methods: The cases were identified from the database of the Population-based Cancer Registry of Goiaˆnia. The primary site was confirmed from the medical files. For all variables studied, frequencies and linear and polynomial logistic regressions were calculated. The Statistical Package for the Social Sciences and Excel softwares were used. Results: Cervical adenocarcinoma accounted for 7.02% of all cancer cases, between 1998 and 2002. The mean age was 44 years for the in situ form and 52 years for the invasive form, and the age group with the highest incidence was from 45 to 49 years. Adenocarcinoma not otherwise specified (68.1%) and stage I were most frequent. The standardized rate incidence increased from 1.47 per 100,000 to 2.84 per 100,000 in 1988 and 2002, respectively (R2 = 0.424 and P = 0.008). The mortality rates due to cervical adenocarcinoma were 0.89 per 100,000 in 1988 and 0.51 per 100,000 in 2002. Conclusions: An increasing incidence of cervical adenocarcinoma was observed in Goiaˆnia, although the mortality rate remained stable. Key Words: Adenocarcinoma, Incidence, Mortality, Trends, Uterine cervix, Goiaˆnia (Int J Gynecol Cancer 2009;19: 694Y698)
T
he epidemiology of cervical cancer is related to women’s standard of living. Thus, for underdeveloped countries, cervical cancer has a high incidence and may be the second most common type of female cancer.1 Until the 1970s, cervical adenocarcinoma represented approximately 10% of cervical cancers. At the beginning of the 1980s, studies showed a prevalence higher than 20%.2Y4 Populationbased studies conducted in North America, Europe, and Asia have shown a decrease of 40% in the incidence rate of squamous cell *Population-Based Cancer Registry of Goiaˆnia, Goia´s Anticancer Association, Goiaˆnia, Brazil; †Descriptive Epidemiology Production Group, International Agency for Research on Cancer, Lyon, France; Departments of ‡Radiotherapy, and §Gynecology and Breast, Arau´jo Jorge Hospital, Goiaˆs Anticancer Association, Goiaˆnia, Brazil. Received September 7, 2008, and in revised form January 12, 2009. Accepted for publication January 15, 2009. Address correspondence and reprint requests to Ruffo Freitas-Junior, MD, PhD, Gynecology and Breast Department, Arau´jo Jorge Hospital, Goia´s Anticancer Association, Rua 239, n.181 Leste Universitario, 74605-070, Goiaˆnia, GO, Brazil. E-mail:
[email protected]. Copyright * 2009 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1111/IGC.0b013e3181a12ea6
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carcinoma (SCC) and an increase of 30% in the incidence of cervical adenocarcinoma, compared with the 1970s,4Y8 especially among women younger than 40 years and of high socioeconomic level.4,9,10 The prognosis for cervical adenocarcinoma has been shown to be worse than for SCC, with a metastatic rate of 12.9% (P G 0.001) and a risk of death that is 4 times greater than for SCC.11,12 In Latin America, little information on cervical adenocarcinoma is available. The data that do exist demonstrate that the incidence rates for adenocarcinoma of the uterine cervix have been increasing11 and that the prognosis for this neoplasia is worse than for SCC.11,13 The aims of this study were to describe the epidemiological profile and analyze the incidence and mortality trends for adenocarcinoma of the uterine cervix in Goiaˆnia, GO, Brazil.
PATIENTS AND METHODS This was a retrospective study on the cervical adenocarcinoma cases registered between 1988 and 2002 using the database of the Population-based Cancer Registry of Goiaˆnia. The primary site and histological diagnosis according to the International Classification of Diseases, Third Edition14 were then confirmed from the patients’ anatomopathological examinations. The eligibility for case inclusion was based on place of residence and primary site. Patients whose primary tumor location
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was not the uterine cervix and those who were not living in the city of Goiaˆnia at the time of the diagnosis were excluded from the study. The date of the cancer diagnosis among patients living in Goiaˆnia had to be subsequent to when they started to live in this city. Mortality data were collected from death certificates issued by the Municipal Health Department of Goiaˆnia for all of the patients who presented cervical adenocarcinoma. The Population-based Cancer Registry of Goiaˆnia has been collecting and processing data on both new cases and mortality every year since 1988. Data are collected from laboratories, hospitals, and clinics specializing in the diagnosis and treatment of oncological patients in Goiaˆnia, and mortality data come from the Municipal Health Department of Goiaˆnia. These data are collected on a specific form and are then typed into a database for analysis.15,16 The quality of the information follows the recommendations of the International Agency for Research on Cancer,17 and histological confirmation is the procedure that ensures the quality of the diagnosis. The extent of disease was divided as in situ, localized, regional to nodes, and distant metastasis, according to the database of the Population-based Cancer Registry of Goiaˆnia, as recommended by International Agency for Research on Cancer.17 The statistical analysis was performed by characterizing the sample in frequencies and means. The crude incidence and mortality rates were calculated and standardized according to the worldwide population.18 To calculate coefficients of incidence and mortality, the estimated annual populations furnished by DATASUS were used.19 The associations between the variables were evaluated using the W2 test. Linear and polynomial regressions were used to draw up the best trend model for cervical adenocarcinoma by means of the Statistical Package for the Social Sciences software for the databases and statistical analyses and the Excel 2003 spreadsheet editing software for the tables and graphs. The significance level was set at 5%. This project was approved by the Ethics Committee of Hospital Arau´jo Jorge of the Goia´s Anticancer Association and was registered under the number 024/2006 in accordance with the regulations for research on human beings of the Brazilian Government Resolution National Health Council-Brazil 196/96.20
RESULTS This study included 248 patients with a diagnosis of cervical adenocarcinoma and 70 deaths due to this neoplasia in Goiaˆnia between 1988 and 2002.
Cervical Adenocarcinoma Rate in Goiaˆnia
Adenocarcinoma of the uterine cervix accounted for 7.02% of the cases of malignant neoplasia of the uterine cervix (248/3531) collected in the Population-based Cancer Registry of Goiaˆnia. From 1988 to 1995, the number of new cases recorded in Goiaˆnia was on average 12 cases per year, whereas from 1996 to 2002, the average went up to 21 cases per year. The mean age of the patients with a diagnosis of adenocarcinoma of the uterine cervix with in situ extent was 44 years, and it was 52 years for invasive cervical adenocarcinoma. It was observed that in situ cervical adenocarcinoma occurred in patients who were 8 years younger than those with invasive adenocarcinoma. This neoplasia affected women between the ages of 35 and 60 years, and the age group with the greatest number of cases was from 45 to 49 years. The frequency of cervical adenocarcinoma cases went down approximately 50% after the age of 60 years. Regarding the histological subtype, adenocarcinoma not otherwise specified was the most frequent type, accounting for 68.1% (169/248) of the patients, followed by endometrioid with 11.3% (28/248), papillary with 9.7% (24/248), and mucinous with 6.5% (16/248). In comparing the prognosis between the histological subtypes, it was observed that the risk of death due to mucinous adenocarcinoma was 3.64 times greater (95% confidence interval, 1.30Y10.19; P = 0.008) than for the other histological types, thus presenting a worse prognosis. The coefficient for the crude incidence of cervical adenocarcinoma in 1988 was 2.44 per 100,000, and in 2002, it was 4.74 per 100,000. The coefficients for the standardized incidence rate were 1.47 per 100,000 in 1988 and 2.84 per 100,000 in 2002. The coefficient for mortality due to cervical adenocarcinoma in 1988 was 0.89 per 100,000, and in 2002, it was 0.51 per 100,000. The mortality-incidence (MI) ratio, defined as the number of deaths recorded during the year divided by the number of new cases recorded during the same year, was 28.59% for the patients analyzed in this study. Figure 1 shows the crude coefficients for incidence and mortality in Goiaˆnia from 1988 to 2002. Analysis of the incidence trends for adenocarcinoma of the uterine cervix showed that there was an increase in the incidence of this neoplasia. It went up by 75% from 1988 to 2002 in Goiaˆnia. The 2 models giving the best predictions of the increase in cervical adenocarcinoma for this period were identified. Univariate linear regression showed a moderate determination coefficient of R2 = 0.424 and P = 0.008 (Fig. 2). Polynomial regression also showed a moderate determination coefficient of R2 = 0.441 and P = 0.03 (Fig. 3).
FIGURE 1. Crude incidence rate (CIB) and crude mortality rate (CMB) of the cervix adenocarcinoma in Goiaˆnia from 1988 to 2002. * 2009 IGCS and ESGO
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FIGURE 2. Incidence trends of the cervix adenocarcinoma in Goiaˆnia from 1988 to 2002 using a linear univariate regression model. Analysis of the mortality trends showed that the mortality rate remained stable. The best statistical model was from polynomial regression, which showed a weak determination coefficient without any statistically significant association. The test values were R2 = 0.08 and P = 0.272 (Fig. 4).
DISCUSSION Cancer of the uterine cervix has been occupying a prominent position in the morbidity-mortality rates among the female population, especially in developing countries.21 In Goiaˆnia, cervical adenocarcinoma accounted for 7.02% (248/3531) of the cases of cancer of the uterine cervix. However, other centers have reported that adenocarcinoma accounts for up to 20% of the cases of malignant neoplasia of the uterine cervix.5 Another study conducted in Goiaˆnia, considering all cervical cancers, showed that the SCC was the most frequent (52.2%), followed by carcinoma no other specification (12.2%).11 The mean age for in situ cervical adenocarcinoma related in other series was 37 years.13,22 This form has been found to occur more in women 10 to 20 years younger than does the invasive form.13,22 In the present study, it was observed that the mean age for cervical adenocarcinoma was 52 years, and there was an 8-year difference in age between the invasive and in situ forms (lower for in situ). Hence, our patients were older than those described in previous studies.23,24 The greatest number of cases was observed between the ages of 45 and 49 years. Their percentages of types were 14.5% in situ, 52% invasive, and 8.9% metastatic adenocarcinoma. Lee et al23
found that 85% of their patients with adenocarcinoma of the uterine cervix had in situ disease and that 9 of 10 cases were minimally invasive. They concluded that in situ cervical adenocarcinoma was the precursor for invasive adenocarcinoma of the uterine cervix, with a mean interval between clinically detecting the in situ and invasive forms of 5 years, thus providing backing for the results from the present study. Adenocarcinoma not otherwise specified was the most frequent type in Goiaˆnia (68.1%). In other studies, the mucinous type accounted for 70% to 80% of the cases of adenocarcinoma,25 and the endometrioid corresponded to 20%.26 The frequencies of the histological types of cervical adenocarcinoma differed from those reported in the literature, about the mucinous and endometrioid types. In our analysis, adenocarcinoma of the mucinous type was identified as a histological subgroup with worse prognosis, for which the risk of death was 3 times greater than in the other types (3.643; 95% confidence interval, 1.302Y10.192; P = 0.008). It might be inferred that there was a bias in the histological classification of these tumors in Goiaˆnia, or that this could be a particular characteristic of the population studied. This information may be the subject of future studies because these cases did not undergo any review of their histological classification. During the present study, a significant increase in the incidence of cervical adenocarcinoma was observed. This was particularly so from 1996 onwards, with an increase of 75% over the remainder of the study period. We believe that one of the hypotheses for the increased rate of cervical adenocarcinoma was the implementation of the National Program for Prevention of Cancer of the Uterine Cervix in Brazil.27 This health policy increased the
FIGURE 3. Incidence trends of the cervix adenocarcinoma in Goiaˆnia from 1988 to 2002 using a polynomial univariate regression model.
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Cervical Adenocarcinoma Rate in Goiaˆnia
FIGURE 4. Mortality trends of the cervix adenocarcinoma in Goiaˆnia from 1988 to 2002 using a polynomial univariate regression model. diagnosis rate among women younger than 55 years. This differed from what was observed by Bergstrom et al,28 who stated that the increase in the incidence of cervical adenocarcinoma did not seem to be influenced by screening programs. One of the possible factors for this affirmation must be that patients with adenocarcinoma had significantly more false-negative results on their most recent Papanicolaou test than patients with SCC.29 The increase in the incidence of cervical adenocarcinoma found in Goiaˆnia is in agreement with other authors.4,5,9,30 Visioli et al7 stated that the impact of this neoplasia could increase in the future if no specific preventive strategies were implemented. The mortality rate due to cervical adenocarcinoma in Goiaˆnia remained stable during the period observed. According to Liu et al,5 there was a reduction in the mortality because of cervical adenocarcinoma in 3 provinces of Canada. In analyzing the MI ratio, an increase was observed in the years 1996 and 1997, which was probably because of the implementation of prevention campaigns. In 2001, there was a decrease in this ratio, reflecting a reduction in mortality, which may have been a demonstration of the efficiency of the treatment and improvement in accessibility for patients. In the present study, statistical models for the incidence and mortality rates for adenocarcinoma of the uterine cervix in Goiaˆnia were determined. These models reflect the behavior of adenocarcinoma of the uterine cervix in Goiaˆnia and confirm the increase in the incidence of cervical adenocarcinoma that was previously described.
CONCLUSIONS Thus, we conclude from this study that there was a 75% increase in the incidence of adenocarcinoma of the uterine cervix in Goiaˆnia. The mortality rate due to adenocarcinoma remained stable during the period analyzed, with a slight decrease in the MI rate from 2001 onwards.
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