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Age-period-cohort effect on mortality from cervical cancer

Abstracts

OBJECTIVE

To estimate the effect of age, period and birth cohort on mortality from cancer of the cervix.

METHODS

Mortality data for cervical cancer in women aged over 30, between1980 and 2009, for the municipalities of Rio de Janeiro and Sao Paulo, Southeastern Brazil,were extracted from the Mortality Information System. The estimated annual percentage change was calculated for the periods 1980-1994 and 1995-2009. Age, period and cohort effects were assessed employing the Poisson regression model, using estimated functions, deviations, curvatures and drift through the library Epi statistical program R version 2.7.2.

RESULTS

The average mortality rate per 100,000 women for the period in Rio de Janeiro was 15.90 and 15.87 in Sao Paulo. There was a significant reduction in mortality from cervical cancer in the two periods (1980-1994 and 1995-2009) in both Rio de Janeiro, -1.20% (95%CI -2.20;-0.09) -1.46% (95%CI -2.30;0.61) and in Sao Paulo, -2.58% (95%CI -3.41;1.76) and -3.30% (95%CI -4.30;2.29). The analysis of effects of curvature indicated reduction in deaths in successive cohorts (RR < 1 in women born after the 1960s). There was marked reduction in relative risk (RR) from the 2000s onwards.

CONCLUSIONS

The study showed that, in the time period analyzed, the period had an effect on the reduction in mortality rates for cervical cancer, bearing in mind that there was a protective effect (RR < 1) from the year 2000 onwards and in women born after the 1960s

Uterine Cervical Neoplasms, mortality ; Cohort Effect ; Period Effect ; Age Effect ; Logistic Models


OBJETIVO:

Estimar o efeito da idade, período e coorte de nascimento na mortalidade por câncer do colo do útero.

MÉTODOS:

Foram analisados dados de mortalidade por câncer do colo do útero em mulheres ≥ 30 anos nos municípios do Rio de Janeiro, RJ, e São Paulo, SP, de 1980 a 2009. Os dados foram extraídos do Sistema de Informação Sobre Mortalidade. A variação percentual anual estimada foi calculada para os períodos de 1980-1994 e 1995-2009. O efeito da idade, período e coorte de nascimento foi calculado pelo modelo de regressão de Poisson, utilizando funções estimáveis: desvios, curvaturas e drift , por meio da biblioteca Epi do programa estatístico R versão 2.7.2.

RESULTADOS:

A taxa de mortalidade média do período por 100.000 mulheres foi 15,90 no Rio de Janeiro e 15,87 em São Paulo. Houve redução significativa na mortalidade por câncer do colo do útero nos dois períodos: no Rio de Janeiro, -1,20% (IC95% -2,20;-0,09) e -1,46% (IC95% -2,30;-0,61), e em São Paulo, -2,58% (IC95% -3,41;-1,76) e -3,30% (IC95% -4,30;-2,29). A análise da curvatura dos efeitos indicou tendência de redução do risco de morte nas sucessivas coortes (RR < 1 nas mulheres nascidas após a década de 1960). Observou-se redução acentuada no risco relativo (RR) a partir dos anos 2000.

CONCLUSÕES:

O estudo evidenciou efeito de período na redução das taxas de mortalidade por câncer do colo do útero no período analisado, tendo em vista que houve efeito de proteção (RR < 1) a partir dos anos 2000 e nas mulheres nascidas após a década de 1960.

Neoplasias do Colo do Útero; mortalidade; Efeito de Coortes; Efeito Período; Efeito Idade; Modelos Logísticos


OBJETIVO:

Estimar el efecto de la edad, período y cohorte de nacimiento en la mortalidad por cáncer del cuello del útero

MÉTODOS:

Se analizaron datos de mortalidad por cáncer del cuello del útero en mujeres ≥ 30 años en los municipios de Rio de Janeiro, RJ, y Sao Paulo, SP (Brasil), de 1980 a 2009. Los datos fueron extraídos del Sistema de Información sobre Mortalidad. La variación porcentual anual estimada fue calculada para los períodos de 1980-1994 y 1995-2009. El efecto de la edad, período y cohorte de nacimiento fue calculado por el modelo de regresión de Poisson, utilizando funciones estimables: desviaciones, curvaturas y drift, por medio de la biblioteca Epi del programa estadístico R versión 2.7.2.

RESULTADOS:

La tasa de mortalidad promedio del período por 100.000 mujeres fue 15,90 en Rio de Janeiro y 15,87 en Sao Paulo. Hubo reducción significativa en la mortalidad por cáncer del cuello de útero en los dos períodos, en Rio de Janeiro: 1,20% (IC95% -2,2;-0,09) -1,46% (IC95% -2,30;-0,61), y en Sao Paulo: 2,58% (IC95% -3,41;-1,76) y -3,30% (IC95% -4,30;-2,29). El análisis de la curvatura de los efectos indicó tendencia de reducción de muerte en las sucesivas cohortes (RR ˂ 1 en las mujeres nacidas posterior a la década de 60). Se observó reducción acentuada en el RR a partir de los años 2000.

CONCLUSIONES

: El estudio evidenció efecto de período en la reducción de las tasas de mortalidad por cáncer del cuello del útero en el período analizado. Teniendo en cuenta que hubo efecto de protección (RR˂1) a partir de los años 2000, y en las mujeres nacidas posterior a la década de 1960.


INTRODUCTION

Cervical cancer is a preventable neoplasia. It is a disease with a well-documented natural history, with well-defined stages and slow progression of lesions. These characteristics mean it can be detected at an early, treatable stage through Pap smear testing. In the last ten years, vaccinations against the HPV virus, a cause of this type of cancer, have become available.1212. Martins LFL, Thuler LC, Valente JG. Cobertura do exame de Papanicolauo no Brasil e seus fatores determinantes: uma revisão da literatura. Rev Bras Ginecol Obstet. 2005;27(8):485-92. DOI: http://dx.doi.org/10.1590/S0100-72032005000800009
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, 1717. Saslow D, Castle PE, Cox JT, Davey DD, Einstein MH, Ferris DG, et al. American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors. CA Cancer J Clin. 2007;57(1):7-28. DOI: http://dx.doi.org/10.3322/canjclin.57.1.7
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, 1919. Taplin SH, Ichikawa L, Yood MU, Manos MM, Geiger AM, Weinmann S, et al. Cervical cancer in women with comprehensive health care acess: attributable factors in screening process. J Natl Cancer Inst. 2005;97(9):675-83. DOI: http://dx.doi.org/10.1093/jnci/dji115
http://dx.doi.org/10.1093/jnci/dji115...

Although measures are taken for its prevention and early detection, cervical cancer is the third most common cancer in women and the fourth most common cause of mortality worldwide. It is the fourth most common cause of death in Brazil, moving to second place in less developed regions.33. Bosseti C, Malvezzi M, Chatenoud L, Negri E, Levi F, La Veccia C. Trends in cancer mortality in Americas, 1970 a 2000. Ann Oncol. 2005;16(3):489-511. DOI: http://dx.doi.org/10.1093/annonc/mdi086
http://dx.doi.org/10.1093/annonc/mdi086...
, 99. Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Cervical Cancer mortality in young women in Europe: patterny and trends. Eur J Cancer. 2000;36(17):2266-71. DOI: http://dx.doi.org/10.1016/S0959-8049(00)00346-4
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, 1414. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statiscs, 2002. CA Cancer J Clin. 2005;55(1):74-108. DOI: http://dx.doi.org/10.3322/canjclin.55.2.74
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, 1818. Silva AG, Girianelli VR, Guamarra CJ, Bustamante-Teixeira MT. Cervical cancer mortality trends in Brazil, 1981-2006. Cad Saude Publica. 2010;26(12):2339-407. DOI: http://dx.doi.org/10.1590/S0102-311X2010001200018
http://dx.doi.org/10.1590/S0102-311X2010...

In Brazil, the first preventative measures for this neoplasia, using the Pap smear, occurred in the state of Sao Paulo in the second half of the 1980s. Public cytopathology laboratories and a referral system to care for positive or suspected cases were set up in municipalities and regions of the state.2121. Zeferino LC, Costa AM, Panetta K, Neves-Jorge J. Screening da neoplasia cervical. J Bras Ginecol. 1996;106(11/12):415-9. Cervical cancer screening campaigns also became part of the Ministry of Health’s Comprehensive Women’s Health Care Program (PAISM) in this decade. There preventative actions were expanded to cover the whole country in 1998, through the National Cervical Cancer Control Program (NCCCP), known as the Life-Woman Program.1313. Osis MJMD. Paism: um marco na abordagem da saúde reprodutiva no Brasil. Cad Saude Publica. 1998;14Suppl 1:25-32. DOI: http://dx.doi.org/10.1590/S0102-311X1998000500011
http://dx.doi.org/10.1590/S0102-311X1998...
, 2020. Teixeira AL, Löwy I. Imperfect tools for a difficult job: Colposcopy, “colpocytogy” and screening for cervical cancer in Brazil. Soc Stud Sci. 2011;41(4):586-608. DOI: http://dx.doi.org/10.1177/0306312711408380
http://dx.doi.org/10.1177/03063127114083...
, 2121. Zeferino LC, Costa AM, Panetta K, Neves-Jorge J. Screening da neoplasia cervical. J Bras Ginecol. 1996;106(11/12):415-9.

Analyses of mortality trends for this type of cancer show a reduction over the last three decades.1818. Silva AG, Girianelli VR, Guamarra CJ, Bustamante-Teixeira MT. Cervical cancer mortality trends in Brazil, 1981-2006. Cad Saude Publica. 2010;26(12):2339-407. DOI: http://dx.doi.org/10.1590/S0102-311X2010001200018
http://dx.doi.org/10.1590/S0102-311X2010...
However, these analyses made use of rates which summarized age and period of death, without considering the effect of the birth cohort, an important factor in understanding the evolution of diseases.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

The age effect represents changes in rates associated with age. The incidence and mortality from chronic illness increase with age.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

Period effect refers to changes in incidence and mortality due to events occurring at specific periods, simultaneously affecting all age groups. Cohort effect is provoked by factors which affect a generation and promote changes of different rates of magnitude in successive age groups and successive periods. Allowing us to evaluate the risk associated with habits and exposures of long duration.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

Using age-period-cohort (APC) models enables period and cohort effects to be separated44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...
and to identify whether changes in mortality rates are correlated with alterations in the level of exposure to the HPV virus (cohort effect) and to co-factors associated with the persistence of lesions caused by the virus or to changes in specific preventative measures (period effect).

This study aimed to estimate the age, period and birth cohort effect (APC) on mortality from cervical cancer.

METHODS

Information on deaths from cervical cancer, cancer of the uterine body and cancer of the uterus, part unspecified, in women aged ≥ 30 in Rio de Janeiro, and Sao Paulo, in Southeastern, Brazil, were included in this study. The data were taken from the Mortality Information System (SIM/DATASUS). The population data were obtained from DATASUS, based on population censuses from 1980, 1991, 2000 and 2010. Projections for intercensal populations for 1st July of the census years were estimated by the Instituto Brasileiro de Geografia e Estatística (IBGE).

The city of Sao Paulo was chosen as the state of Sao Paulo was the first place in Brazil where screening using Pap smears was implemented. The city of Rio de Janeiro was chosen as it is the second largest city in the country, it is located in the Southeast and has similar socio-economic conditions to Sao Paulo.

In the period in which the study took place there were two revisions of the International Statistical Classification of Diseases and Related Health Problems (ICD) underway. In the ninth version, the three digit character for cervical cancer was 180; for cancer of the uterus, part unspecified 179; and for cancer of the body of uterus, 182. The codes from the tenth revision were C53, C55 and C54 respectively. Deaths classified as cancer of the uterus, part unspecified, were redistributed as cervical cancer and cancer of the uterine body according to the proportions of death certificates originally registered for each category for cause, year and age group. Specific mortality rates were calculated according to age groups and mortality rates standardized by the direct method after redistribution using the world standard population as proposed by Segi.55. Doll R, Payne P, Waterhouse J. Cancer incidence in five continents: a technical report. Berlin: Springer-Verlarg; 1966. The redistribution was carried out by correcting cervical cancer mortality rates, considering the large proportion of deaths classified as cancer of the uterus, part unspecified.

The Estimated Annual Percent Change (EAPC) was calculated based on the equation:. in which m was estimated based on the regression model in which the logarithm of mortality rates was the dependent variable and the calendar year the independent variable. This calculation assumes that the rate increases or decreases in a linear fashion year on year, during the entire interval in question. The EAPC was calculated for two consecutive periods: 1980-1994 and 1995-2009.

The age, period and birth cohort effects (APC) were calculated using the Poisson regression model, which assumes that the number of deaths follows a Poisson distribution. In this model, the effects behave in a multiplicative manner on the rate, so that the expected value of the logarithm of the ratio is a linear function of the age, period and cohort effect:44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

in which denotes the expected mortality rate at age i in the period j , the expected number of deaths at age i in period j , and denotes the population at risk of death at age i in period j : µ represents the mean effect, represents the age group effect i , represents the period effect j and the cohort effect k .

The age groups used were grouped by five year intervals, starting at 30-34 and ending at 75 and over, making a total of ten age groups. The period were also grouped by five year intervals, making six periods (1980 to 1984, 1985 to 1989, 1990 to 1994, 1995 to 1999, 2000 to 2004 and 2005 to 2009) and the birth cohorts started at 1900 and finished in 1979, making a total of 15 cohorts.

The main problem with estimating the parameters of the APC affect is the exact linear relationship between the age, period and cohort factors, which impedes estimation of the complete model. Various methodologies have been proposed to resolve this problem; however, no consensus exists in the literature. It was decided to estimate the parameters of the APC effect using estimable functions: deviations, curves and drift . 44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
,66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

The estimable functions limit the analysis of the effects to their linear combinations and curves. The curves are estimable functions of the parameters and remain constant regardless of the parameterization used.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...
The linear trend of the effects is divided into two components: the first is the linear effect of age and the other is the so-called drift, the linear effect of the cohort period.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...
The longitudinal tendency of age is equal to the sum of age and the gradient of period. in which and are the linear trend of age and of period respectively. Drift represents the linear trend of the logarithm of the rates specific to age. It is equal to the sum of the gradients of period and cohort.in which and are the linear trends for period and cohort, respectively.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...

For this methodology, a cohort and a period were chosen as reference. The specific rates for age and cohort/period of reference will be the RR (relative risk) of each cohort compared to the reference cohort and of each period compared to the reference period. It is advisable to choose central cohorts, as they was more complete than the first and last birth cohorts.44. Clayton D. Schifflers E. Models for temporal variation in cancer rates I: Age-period and Age-Cohort models. Stat Med. 1987;6(4):449-67. DOI: http://dx.doi.org/10.1002/sim.4780060405
http://dx.doi.org/10.1002/sim.4780060405...
, 66. Holford TR. The estimation of age, period and cohort effects for vital rates. Biometrics. 1983;39(2):311-24. DOI: http://dx.doi.org/10.2307/2531004
http://dx.doi.org/10.2307/2531004...
, 77. Holford TR. Undestranding the effects of age, period, and cohort on incidence and mortality rates. Annu Rev Public Health. 1991;12(1):425-57. DOI: http://dx.doi.org/10.1146/annurev.pu.12.050191.002233
http://dx.doi.org/10.1146/annurev.pu.12....
, 1515. Robertson B, Boyle P. Age period-cohort analysis of chronic disease rates I: Modelling approach. J Start Med. 1998;17(12):1305-23. DOI: http://dx.doi.org/10.1016/S0895-4356(99)00033-5
http://dx.doi.org/10.1016/S0895-4356(99)...
In this article, the 196-1964 cohort was used as the reference. The RR of the birth cohorts were adjusted for age and period effect and the RR of the period for birth cohort and age effect. These measures of association and their respective confidence intervals (95%CI) were calculated using Epi 1.1.18 a a Carstensen B, Plummer M, Hills M, Laara E. A package for statistical analysis in epidemiology. Vienna: Institute for Statistics and Mathematics; 2001 [cited 2010 Oct 19]. Available from: http://cran.r-project.org/web/packages/Epi/index.html (R statistic program, version 2.7.2).

The quality of fit was assessed using deviance statistics, defined as two times the logarithm of the estimated likelihood function of the model. The contribution of the effects was assessed by comparing the deviance of the model with the specific effect compared to the complete model (age-period-cohort). Results with p ≤ 0.05 were considered significant. The tests were carried out using the R statistic program version 2.7.2, through the Epi 1.1.18 library, a a Carstensen B, Plummer M, Hills M, Laara E. A package for statistical analysis in epidemiology. Vienna: Institute for Statistics and Mathematics; 2001 [cited 2010 Oct 19]. Available from: http://cran.r-project.org/web/packages/Epi/index.html as shown in Figuras 1 and 2.

Figure 1 .
Cervical cancer mortality rates by birth cohort and age for deaths in the municipalities of Rio de Janeiro, and Sao Paulo, in Southeastern Brazil, 1980 to 2009.

Figure 2 .
Results of the Age-period-cohort model, adjusted for cervical cancer mortality in the municipalities of Rio de Janeiro, and Sao Paulo, in Southeastern Brazil, 1980 to 2009.

Figure 1 shows mortality rates by birth cohort for each age group. Figure 2 shows the effects of age, period and birth cohort based on the complete model. To the left, the mortality rates per 100,000 women by age are shown. The figure to the right of that shows the RR of the periods, adjusted for birth cohort and age effect and RR of birth cohorts adjusted for age and period in which death occurred.

RESULTS

Between 1980 and 2009 there were 9,995 deaths from cancer of the uterus in women aged over 30 in the municipality of Rio de Janeiro (MRJ), and 14,158 in the municipality of Sao Paulo (MSP). Deaths from cervical cancer were predominant in both cities (49.7% in MRJ and 51.9% in MSP).

The mortality rate from cervical cancer in MRJ was 10.76/100,000 women, and from cancer of the uterine body, 2.93/100,000 and for cancer of the uterus, part unspecified, 6.98/100,000 women. In MSP these figures were 11.45/100,000, 3.92/100,000 and 2.98/100,000 women respectively.

After redistributing the deaths classified as being from cancer of the uterus, part unspecified, mean mortality rates of 15.90/100,000 women from cervical cancer and 5.13/100,000 from cancer of the uterine body in MRJ and 15.87/100,000 and 5.75/100,000 women, respectively, in MSP.

The highest mortality rates in the two cities from this neoplasia were observed between 1980 and 1984, the rates declined between 1985 and 1989, although they rose again in the period 1990 and 1994. From 1995 to 1999 onwards there was a decrease in the mortality rates, a trend which continued until 2005 to 2009. This five-year-period had the lowest levels in the series studied (Table 1).

Table 1.
Mortality from cervical cancer (per 100,000 women), in the municipalities of Rio de Janeiro and Sao Paulo, Southeastern Brazil, 1980 to 2009.

The highest mortality rates were in women born between 1900 and 1940, over 20.0 deaths per 100,000 women aged up to 50-54 years old, in both cities. The mortality rates decreased in the younger age groups in each birth cohort, these being under 10.0 deaths per 100,000 in women born after the 1950s and in the age group 40 to 44 (1).

There was an overall decrease in cervical cancer mortality rates in both cities in the EAPC. The EAPC between 1980 and 1994 was -1.20% (95%CI -2.20;-0.09) and -2.58% (95%CI -3.41;-1.76) in MRJ between 1995 and 2009. In Sao Paulo, this was -1.46% (95%CI -2.30;-0.61) and -3.30% (95%CI -4.30;-2.29), respectively. Variations in the age groups showed that the MSP had a greater number of age groups with a statistically significant decrease, compared with MRJ (Table 2).

Table 2.
Estimated annual percentage variation (EAPC) of cervical cancer mortality rates, in the municipalities of Rio de Janeiro, and Sao Paulo, in Southeastern Brazil, 1980 to 2009.

Both age-cohort and age-period models showed better fit to the data than the models containing just age and age-drift. The complete model was significantly better than that with only two factors AP (p < 0.0001) and AC (p < 0.0001). The AC model had as null hypothesis the lack of influence of period effect on mortality rates. And the AP model had as null hypothesis the lack of influence of the birth cohort effect (Table 3)

Table 3.
Adjustments to the models of age-period-cohort effects, for mortality from cervical cancer in the municipalities of Rio de Janeiro, and Sao Paulo, in Southeastern Brazil, 1980 to 2009.

In both cities, there was a progressive increase in cervical cancer mortality rates with age (Figure 2).

In MRJ, a reduced risk of death compared to the reference period (1990 to 1994) was observed between 1985 and 1989 (RR = 0.93; 95%CI 0.89;0.97). There was an increased risk in the 1990s, with the highest value between 1995 and 1999 (RR = 1.12; 95%CI 1.04;1.20), which again decreased in the 2000s, and the lowest value was between 2005 and 2009 (RR = 0.86; 95%CI 0.83;0.92). The period between 1985 and 1989 had RR = 1.04 (95%CI 1.01;1.08) in MSP; there was increased risk in the 1990s, reaching a peak between 1995 and 1999 (RR = 1.22; 95%CI 1.15;1.31), which then fell and continued to do so until 2009 (RR =1.02; 95%CI 0.97;1.07) (Figure 2).

Analysis of mortality in birth cohorts shows an accentuated tendency for risk of death to decrease in successive birth cohorts. There was a high risk of death from this neoplasia for women in both cities between 1900 and 1940. The 1900-1940 birth cohort had an RR = 3.30 (95%CI 2.78;3.86) in MRJ and RR = 2.40 (95%CI 2.05;2.80) in MSP. In both cities, there was a reduction in the rate for the 1930 to 1934 cohort (RR = 1.47; 95%CI 1.33;1.62) in MRJ and in MSP (RR = 1.57; 95%CI 1.45;1.72). After this decade, there was a progressive decrease in the risk of death, becoming < 1 in women born after the reference birth cohort (1960 to 1964); the lowest value was seen in women born in the 1975 to 1979 cohort. In MRJ, the RR was 0.89 (95%CI 0.81;0.96) and in MSP, was 0.85 (95%CI 0.78;0.95) (Figure 2).

DISCUSSION

This study showed a significant difference in mortality from cervical cancer in both cities during the period in question, a significant period effect (national program for controlling cervical cancer) in reducing the risk of death. Lower RRs were observed after the 2000s, above all in women born after the 1960s.

Evaluating the risk of death from cervical cancer according to birth cohort showed that women born between 190 and 1920 had a high risk of death from this neoplasia. Birth cohorts after 1930 a progressively reduced risk of death, with a protective effect (RR < 1) for women born after 1960.

Between 1900 and 1920, cancer was seen as an incurable disease and there were no secondary preventative practices. This may explain the higher risk of death when compared with more recent birth cohorts.11. Alves CMM, Bastos RR, Guerra MR. Mortality due to cancer of the uterine cervix in the state of Minas Gerais, Brazil, 1980-2005: period and cohort analysis. Cad Saude Publica. 2010;26(7):1446-56. DOI: http://dx.doi.org/10.1590/S0102-311X2010000700024
http://dx.doi.org/10.1590/S0102-311X2010...
, 2020. Teixeira AL, Löwy I. Imperfect tools for a difficult job: Colposcopy, “colpocytogy” and screening for cervical cancer in Brazil. Soc Stud Sci. 2011;41(4):586-608. DOI: http://dx.doi.org/10.1177/0306312711408380
http://dx.doi.org/10.1177/03063127114083...

Among women in the 1930 to 1940 birth cohort, the introduction of measures to care for and prevent cancer may have had some influence on mortality rates. In the 1940s, pioneering work among health care professionals started to bring the practice of cytology and colposcopy to Brazil. These preventative and curative measures only reached a small group of the population, as at that time public health care resources prioritized the prevention and treatment of infectious diseases.11. Alves CMM, Bastos RR, Guerra MR. Mortality due to cancer of the uterine cervix in the state of Minas Gerais, Brazil, 1980-2005: period and cohort analysis. Cad Saude Publica. 2010;26(7):1446-56. DOI: http://dx.doi.org/10.1590/S0102-311X2010000700024
http://dx.doi.org/10.1590/S0102-311X2010...
, 2020. Teixeira AL, Löwy I. Imperfect tools for a difficult job: Colposcopy, “colpocytogy” and screening for cervical cancer in Brazil. Soc Stud Sci. 2011;41(4):586-608. DOI: http://dx.doi.org/10.1177/0306312711408380
http://dx.doi.org/10.1177/03063127114083...

The protective effect observed in women born after the 1960s may be related to intensified efforts to prevent and control this neoplasia with the establishing of the PNCCC at the end of the 1990s. This program increased the number of screening tests carried out annually by the Brazilian Unified Health System (SUS) by 81% between 1995 and 2003.2020. Teixeira AL, Löwy I. Imperfect tools for a difficult job: Colposcopy, “colpocytogy” and screening for cervical cancer in Brazil. Soc Stud Sci. 2011;41(4):586-608. DOI: http://dx.doi.org/10.1177/0306312711408380
http://dx.doi.org/10.1177/03063127114083...

There was an increase in the risk of death from this neoplasia during the 1990s, peaking between 1995 and 1999 in both MRJ and MSP, which then declined after 2000 and continued to decline until 2009.

The increased cervical cancer mortality rate in the 1990s may be related to low levels of coverage for the cytology tests at the beginning of the decade. In 1994, 37% of Brazilian women aged 35 to 49 had never had a smear test, in the Southeast the figure was 32%. b b Ministério da Saúde. Instituto Nacional de Câncer. Viva Mulher – Programa Nacional de Controle do Câncer do Colo Uterino. Brasília (DF); 1996. After the NCCCP was established in 1998, availability and access to these tests increased. Data from the National Research by Household Survey (PNAD) between 2003 c c Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios (PNAD) 2003 – Acesso e utilização dos serviços de saúde. Brasília (DF); 2011 [cited 2010 Oct 20]. Available from: http://www.ibge.gov.br/home/estatistica/populacao/trabalhoerendimento/pnad2003/saude/saude2003.pdf and 2008 d d Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios (PNAD) 2008 – Suplemento Saúde. Brasília (DF); 2011 [cited 2010 Oct 20]. Available from: http://www.ibge.gov.br/home/estatistica/populacao/panorama_saude_brasil_2003_2008/default.shtm estimated coverage of 68.7% and 84.5% for protective gynecology in women aged over 25, respectively.

Decreasing mortality rates for this neoplasia related to the effect of the program for prevention and control of cervical cancer (period effect), indicated in this study, are similar to those of other studies carried out in the United Kingdom (1950-1997),16 16. Sasiene P, Adams J. Effect of screening on cervical cancer mortality in England and Wales: analysis of trend with an age, period and cohort model. BMJ. 1999;318(7193):1244-5. DOI: http://dx.doi.org/10.1136/bmj.318.7193.1244
http://dx.doi.org/10.1136/bmj.318.7193.1...
Switzerland (1953-1995)2 2. Bergström R, Sparén P, Adami HO. Trends in cancer of the cervix uteri in Sweden following cytological screening. Br J Cancer. 1999;81(1):159-66. DOI: http://dx.doi.org/10.1038/sj.bjc.6690666
http://dx.doi.org/10.1038/sj.bjc.6690666...
and in the state to Minas Gerais, Southeast, (1980-2005).1 1. Alves CMM, Bastos RR, Guerra MR. Mortality due to cancer of the uterine cervix in the state of Minas Gerais, Brazil, 1980-2005: period and cohort analysis. Cad Saude Publica. 2010;26(7):1446-56. DOI: http://dx.doi.org/10.1590/S0102-311X2010000700024
http://dx.doi.org/10.1590/S0102-311X2010...
The authors of these studies unanimously interpret the results of these studies as best explained by the establishment of a program of screening for cancer than as a birth cohort effect.

These results do not agree with those observed in Shandong, China (1970-1992),1010. Li H, Jin S, Xu H, Thomas DB. The decline in the mortality rates of cervical cancer and plausible explanation in Shandong, China. Int J Epidemiol. 2000;29(3):398-404. DOI: http://dx.doi.org/10.1093/ije/29.3.398
http://dx.doi.org/10.1093/ije/29.3.398...
and in Spain (1951-1991),1111. Llorca J, Prieto MD, Delgado-Rodriguez M. Increase in cervical cancer mortalility in Spain 1951-1991. J Epidemiol Community Health. 1999;53(7):408-11. DOI: http://dx.doi.org/10.1136/jech.53.7.408
http://dx.doi.org/10.1136/jech.53.7.408...
as the reduction in mortality rates was related to cohort effect in function of lowered exposure to risk factors related to this type of cancer. This hypothesis is coherent, considering that in China, brothels were closed, prostitution banned and the single child per couple policy instituted. In the same way, in Spain, before 1975 the low mortality rates found there were associated with becoming sexually active at a later age, a reduced number of sexual partners, delayed widespread use of hormonal contraceptives as well as the fact that adultery was criminalized until 1976. Campaigns to combat cervical cancer were regionalized and, in the period studied, only covered a small part of the female population.1010. Li H, Jin S, Xu H, Thomas DB. The decline in the mortality rates of cervical cancer and plausible explanation in Shandong, China. Int J Epidemiol. 2000;29(3):398-404. DOI: http://dx.doi.org/10.1093/ije/29.3.398
http://dx.doi.org/10.1093/ije/29.3.398...
, 1111. Llorca J, Prieto MD, Delgado-Rodriguez M. Increase in cervical cancer mortalility in Spain 1951-1991. J Epidemiol Community Health. 1999;53(7):408-11. DOI: http://dx.doi.org/10.1136/jech.53.7.408
http://dx.doi.org/10.1136/jech.53.7.408...

One of the limitations of this study was the quality of information, bearing in mind the large number of deaths classified as “cancer of the uterus, part unspecified”, especially in the first years of the series studied. An attempt was made to correct this problem by redistributing these deaths according to the proportion of certificates registered for each category by age and year of death.

Another limitation concerns the APC models, which are still in development. The results obtained vary according to the assumptions used in constructing the models. In the last decade, articles have been published discussing methodological aspects in the specifications of the models and in resolving the problem of not identifying the complete model.8, a a Carstensen B, Plummer M, Hills M, Laara E. A package for statistical analysis in epidemiology. Vienna: Institute for Statistics and Mathematics; 2001 [cited 2010 Oct 19]. Available from: http://cran.r-project.org/web/packages/Epi/index.html

The Poisson model assumes the equality of mean and variance, difficult to achieve in practice, and variance is generally greater than the mean. This phenomenon is known as overdispersion and, when not detected and corrected, leads to an incorrect estimation of standard deviation and, consequently, an incorrect assessment of the significance of the parameters. In the analyses in this study, the Poisson models were adjusted because the adjusted results for this distribution did not differ from those obtained from the negative binomial.

This study showed the importance of establishing and consolidating the NCCC Pin reducing the risk of death from cervical cancer, even in women with greater exposure to risk factors for this neoplasia. There was a protective effect (RR < 1) for women born after the 1960s, who were influenced by the sexual and cultural revolution which began in this decade (cohort effect) and underwent changes in lifestyle which increased their exposure to risk factors associated with this type of cancer.2020. Teixeira AL, Löwy I. Imperfect tools for a difficult job: Colposcopy, “colpocytogy” and screening for cervical cancer in Brazil. Soc Stud Sci. 2011;41(4):586-608. DOI: http://dx.doi.org/10.1177/0306312711408380
http://dx.doi.org/10.1177/03063127114083...
, 2121. Zeferino LC, Costa AM, Panetta K, Neves-Jorge J. Screening da neoplasia cervical. J Bras Ginecol. 1996;106(11/12):415-9. The possible increased risk of infection with the HPV virus did not have a greater repercussion on mortality due to the existence of effective protective measures.

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Publication Dates

  • Publication in this collection
    June 2013

History

  • Received
    9 Mar 2012
  • Accepted
    21 Aug 2012
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