RESUMEN

Objetivo:

Estimar la incidencia de cáncer de cuello uterino y sobrevida de pacientes con esta enfermedad según subtipo histológico y estadios en Manizales, Colombia para el periodo 2008-2012, y comparar cambios en la sobrevida con el quinquenio anterior.

Materiales y métodos:

A partir de datos poblacionales, se estandarizaron las tasas de incidencia según la edad para cada subtipo histológico. Se realizó un seguimiento activo y pasivo para determinar el estado vital y la causa de muerte a 60 meses. Se ajustaron funciones de Kaplan-Meier y modelos de Cox para estimar la sobrevida global y según covariables.

Resultados:

Se presentaron 217 casos nuevos para una incidencia media de 17,8 por 100 000 mujeres-año. Hubo mayor frecuencia de estadios III-IV en pacientes de nivel socioeconómico medio y bajo. La sobrevida a cinco años fue de 68,9%; la edad (>70 años) se asoció con menor sobrevida (p < 0,001). El riesgo de fallecer fue 90% mayor en pacientes con muestra histológicas no diferenciadas o desconocidas comparado con el carcinoma escamocelular (hazard ratio [HR] 1,9; IC 95%: 1,1-3,3); 1,7 veces mayor para personas mayores de 70 años (HR 2,7; IC 95%: 1,6-4,8); y tres veces mayor para estadio III (HR 4,3; IC 95%: 1,8-10,2) y siete veces mayor para estadio IV (HR 8,7; IC 95%: 3,6-20,1) en comparación con el estadio I.

Conclusión:

La incidencia de cáncer del cuello uterino en Manizales es similar a la global y a la continental, y fue más baja que otras ciudades colombianas con características similares. Hubo mayor frecuencia de estadios avanzados en mujeres de bajo nivel socioeconómico. La sobrevida se asoció con la edad, el subtipo histológico y la estadificación.

Palabras clave:
Neoplasias del Cuello Uterino; Incidencia; Sobrevida; Colombia

ABSTRACT

Objective:

To estimate the cervical cancer incidence and survival rates by histological subtype and stage in Manizales, Colombia during 2008-2012; and to compare the survival rate to the one from the previous five years.

Materials and methods:

Using population-based data, incidence rates by age were standardized for each histological subtype. Active and passive follow-up was performed to determine vital status and cause of death at 60 months. The Kaplan-Meier method and Cox models were adjusted to estimate overall survival by each covariant.

Results:

A total of 217 new cases were observed; with a mean incidence of 17.8 per 100,000 woman-years. Stages III-IV were more frequently observed in patients of medium and low socioeconomic status. At 5 years, the survival rate was 68.9%; ages over 70 years were associated with lower survival rates (p<0.001). Risk of death was 90% higher in patients with undifferentiated or unknown histological samples, when compared with those with squamous cell carcinoma (HR 1.9, 95% CI: 1.1-3.3). Likewise, the risk of death was 1.7 times higher for patients aged over 70 years (HR 2.7, 95% CI 1.6-4.8); and it was also found to be 3 times higher for stage III (HR 4.3, 95% CI: 1.8-10.2) and 7 times higher for stage IV (HR 8.7, 95% CI: 3.6-20.1), when compared with stage I.

Conclusion:

The incidence rate of cervical cancer in Manizales was found to be similar to the global and continental rates and lower than those from other Colombian cities with similar characteristics. Advanced stages were more frequent in women of low socioeconomic status. Survival was associated with age, histological subtype and staging.

Keywords:
Uterine Cervical Neoplasms; Incidence; Survival; Colombia

INTRODUCTION

Cervical cancer is the second most common cancer in women, after breast cancer and followed by endometrial and ovarian cancers; it influences the global incidence of cancer, especially in Latin American, Southeast Asian, and African countries ¹1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD 3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based regis tries in 71 countries. Lancet. 2018;391(10125):1023-75. doi: 10.1016/S0140-6736(17)33326-3.
https://doi.org/10.1016/S0140-6736(17)33... . Despite scientific advances in surgery, chemotherapy and radiotherapy, global survival has had discrete improvements in the last two decades, even at the early stages of the disease ²2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
https://doi.org/10.3322/caac.21492.... . GLOBOCAN 2018 showed a worldwide incidence of 14 cases per 100,000 women. In South America the cumulative incidence of cervical cancer is 2.5% with respect to world population²2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
https://doi.org/10.3322/caac.21492.... .

The CONCORD 3 study, which evaluated five-year survival for the 18 most common cancers on five continents, showed a 50-70% cervical cancer survival in Central and South America, Asia, and Europe; 70% or more in Japan, Korea, Taiwan, Denmark, Norway, Switzerland, and Cuba; 60-69% in 29 other countries; and 50-59% in Argentina, Ecuador, Martinique, Peru, Uruguay, India, Kuwait, Latvia, Lithuania, Bulgaria, Poland, Russia, and Malta¹1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD 3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based regis tries in 71 countries. Lancet. 2018;391(10125):1023-75. doi: 10.1016/S0140-6736(17)33326-3.
https://doi.org/10.1016/S0140-6736(17)33... .

Manizales is a medium-sized city located on the central mountain range of the Colombian Andes, with a population of nearly 400,000 inhabitants mostly concentrated in urban areas (93% urbanization). During the period 2003-2007, the city reported an age-adjusted incidence rate of 19.9 per 100,000 women per year ³3. López Guarnizo G, Arias Ortiz N, Arboleda Ruiz W. Cancer incidence and mortality in Manizales 2003-2007. Colomb Méd. 2012;43(4):281-9.. Other Colombian cities, such as Bucaramanga and Cali reported incidence rates of about 20 per 100,000 women per year, and Pasto with 27 cases per 100,000 ⁴4. Pardo C, Cendales R. Incidencia, mortalidad y prevalencia de Cáncer en Colombia 2007-2011. Bogotá: Instituto Nacional de Cancerología; 2015 [citado el 15 de febrero de 2019]. Disponible en: https://www.cancer.gov.co/files/libros/archivos/incidencia1.pdf.. During 2008-2012, the highest incidence was found in Barranquilla with 26.6 ⁵5. Moranth RV, Navarro E. Cancer incidence and mortality in Barranquilla, Colombia. 2008-2012. Colomb Med. 2018;49(1):55-62. doi: 10.25100/cm.v49i1.3627.
https://doi.org/10.25100/cm.v49i1.3627... , followed by Pasto with 18 new cases per 100,000 women-year ⁶6. Yepez MC, Jurado DM, Bravo LM, Bravo LE. Trends in cancer incidence and mortality in Pasto, Colombia. 15 years experience. Colomb Med. 2018;49(1):42-54. doi: 10.25100/cm.v49i1.3616.
https://doi.org/10.25100/cm.v49i1.3616... ; a lowest incidence in Cali with 15.3 ⁷7. Bravo LE, Arboleda OI, Ramirez O, Durán A, Lesmes MC, Rendler-García M, et al. Editorial. Cali, Colombia, C/Can 2025 aprendizaje clave: desafío de ciudades contra el cáncer. Colomb Med. 2017;48(2):39-40. and in Bucaramanga with 13 new cases per 100,000 women-year ⁸8. Uribe CJ, Serrano SE, Hormiga CM. Incidencia y mortalidad por cáncer en Bucaramanga, Colombia. 2008-2012. Colomb Med. 2018;49(1):73-80..

A previous study about cervical cancer survival in Manizales during 2003-2007 found that overall survival at five years was 51.4%, with a higher probability of survival in women from the contributory social security regime, compared to those in the subsidized regime and special or exception regimes. By correlating survival with socioeconomic position, differences found could be explained by associated comorbidities, delays in diagnosis and barriers to accessing timely treatment ⁹9. Arias Ortiz NE, De Vries E. Health inequities in cancer survival in Manizales, Colombia: a population-based study. Colomb Med. 2018;49(1):63-72. doi: 10.25100/cm.v49i1.3629.
https://doi.org/10.25100/cm.v49i1.3629... .

These results increased the need to analyze a new period to monitor the behavior of incidence and survival, to obtain population-based epidemiological information with international standards that would allow us to know the performance of the health system as a whole and to explore the improvements or setbacks regarding survival. To this end, the present study aimed to estimate the incidence of cervical cancer and survival of patients, according to histological subtype and stages in Manizales, Colombia, during 2008-2012, and to compare changes in survival compared to survival in the previous five-year period.

METHODS

Population and sample

This is an observational, retrospective, longitudinal and analytical study conducted, based on population data to estimate incidence and survival. According to official projections, data from 200,000 women living in the urban and rural jurisdictions of Manizales, department of Caldas, Colombia, were analyzed. The city has a population-based cancer registry indexed by the International Association of Cancer Registries and the International Agency for Research on Cancer (IARC) and meets international quality standards ¹⁰10. Arias-Ortiz N, López-Guarnizo G. Evaluación de Calidad de los Datos del Registro Poblacional de Cáncer de Manizales, Colombia. Revista Colombiana de Cancerología. 2013;17(4):132-141.^,1111. Tyczynski J, Demaret E, Parkin D. Standards and Guidelines for Cancer Registration in Europe [Internet]. IARC; 2003 [citado el 15 de febrero de 2019]. Disponible en: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Technical-Publications/Standards-And-Guidelines-For-Cancer-Registration-In-Europe-2003.
https://publications.iarc.fr/Book-And-Re... .

Procedure

Incidence estimates

The incidence count included all new cases diagnosed between January 1, 2008 and December 31, 2012, which topographic codes corresponded to those defined in the CONCORD 3 study (C53.0-C53.9 of the ICD-10). The histological typing (tumor morphology) was coded from the clinical history or from the biopsy reports and pathological anatomy studies, following the rules of the International Classification of Diseases for Oncology, third edition, first revision (ICD-O 3.1), the histological groupings of the CONCORD 3 study, and the rules of the National Comprehensive Cancer Network 2019 (NCCN) ¹²12. Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Cervical cancer, version 3. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001.
https://doi.org/10.6004/jnccn.2019.0001... .

Initially the histological types were grouped in eight categories and later reduced to three, called “large groups”, distributed in squamous cell carcinoma, adenocarcinoma, and a category that grouped other histological types and undifferentiated or unspecified tumors. The clinical staging was done according to the classification of the International Federation of Gynecology and Obstetrics (FIGO) ¹³13. Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet. 2018;145(1):129-135. doi: 10.1002/ijgo.12749.
https://doi.org/10.1002/ijgo.12749... .

The incidence rate denominator includes the official data from the projections of the total women population by five-year groups from 0 to 85 years and older ¹⁴14. DANE. Estimación y proyección de población nacional, departamentales y municipales por grupos quinquenales de edad y edades simples de 0 a 26 años, 1985-2020 [Internet]. DANE; 2007 [citado el 26 de abril de 2019]. Disponible en: https://www.dane.gov.co/index.php/estadisticas-por-tema/demografia-y-poblacion/proyecciones-de-poblacion.
https://www.dane.gov.co/index.php/estadi... . Direct method standardization was applied as per Segi’s world population ¹⁵15. Boniol M, Heanue M. Age-standardisation and denominators. En: Curado M, Shin B, Storm H, Ferlay J, Heanue M, Boyle P, editores. Cancer Incidence in five continents, Vol IX [Internet]. International Agency for Research on Cancer; 2007. Disponible en: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Scientific-Publications/Cancer-Incidence-In-Five-Continents-Volume-IX-2007.
https://publications.iarc.fr/Book-And-Re... . Incidence rates by histological type were calculated for the period 2008-2012 and for each single calendar year.

Survival estimates

All new cases from the studied period were included, except those which only source of information was the death certificate, since these cases have no follow-up time and would underestimate survival. Passive monitoring was done taking into account the date of the last medical care or the last social security payment report, and on the vital status in administrative and civil databases in the country (the Unique Database of Affiliates of the General System of Social Security in Health, the Master Database of Compensated Affiliates of the Health Resources Administrator, the voter registry of the National Registry of Civil Status, and the database of the Attorney General’s Office). The date of death and cause of death were verified, case by case, in the module of the Unique Registry of Affiliates of the division of Vital Statistics of the Territorial Health Directorate of Caldas. In patients whose complete information about their vital status was not obtained from administrative databases, an active follow-up was carried out by consulting clinical records in oncological centers. The follow-up was carried out until December 2018, truncated at 60 months; the patients who died from causes other than cervical cancer were considered as censored.

Study variables

Age, histological type, social security regime, socioeconomic level and clinical stage at diagnosis were analyzed as independent explanatory variables of survival. The variables age, histological type and staging at diagnosis have been used as predictors in other survival studies and are considered necessary adjustment variables in oncological studies ¹⁶16. Booth CM, Li G, Zhang-Salomons J, Mackillop WJ. The impact of socioeconomic status on stage of cancer at diagnosis and survival: A population-based study in Ontario, Canada. Cancer. 2010;116(17):4160-7. doi: 10.1002/cncr.25427.
https://doi.org/10.1002/cncr.25427... . The cut-off point for age was set based on previous studies that have used ages between 65 and 75 years in comparison with younger groups of patients ¹⁷17. Bradley CJ, Given CW, Roberts C. Disparities in cancer diagnosis and survival. Cancer. 2001;91(1):178-88. doi: 10.1002/1097-0142(20010101)91:1(178::aid-cncr23)3.0.co;2-s.
https://doi.org/10.1002/1097-0142(200101... ^,1818. Quaresma M, Coleman MP, Rachet B. 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales, 1971-2011: a population-based study. Lancet. 2015;385(9974):1206-18. doi: 10.1016/S0140-6736(14)61396-9.
https://doi.org/10.1016/S0140-6736(14)61... .

The socioeconomic stratum of the place of residence at the time of diagnosis was the indicator of socioeconomic position. In Colombia, this indicator is defined in categories from 1 to 6 according to the external and internal physical characteristics of the homes, ranging from the purely functional and indispensable to the aesthetic, ornamental and sumptuous characteristics. In this regard, 1 and 2 correspond to the “low” socioeconomic stratum; 3 and 4, “medium”; and 5 and 6, “high” ⁹9. Arias Ortiz NE, De Vries E. Health inequities in cancer survival in Manizales, Colombia: a population-based study. Colomb Med. 2018;49(1):63-72. doi: 10.25100/cm.v49i1.3629.
https://doi.org/10.25100/cm.v49i1.3629... . In the analysis, the categories “medium” and “high” were regrouped in order to have enough observations in each group, because in the richest strata the proportion of the population is lower, and the frequency of cervical cancer is very low.

In Colombia, health insurance financed by contributions from workers and employers (contributory system) is mandatory for dependent employees and partially voluntary for independent workers. A small proportion (<5%) of the population working in certain public sectors, such as defense and education, has exceptional or special health insurance plans (special or exceptional regime). Poor population is covered by a subsidized system founded through taxes (subsidized regime) ¹⁹19. Congreso de la República (Colombia). Ley del Sistema General de Seguridad Social. Ley 100 de 1993 [Internet]. Diario Oficial No. 41.148 de 23 de diciembre de 1993. Bogotá, D. C.; 1993 [citado el 13 de abril de 2020]. Disponible en: https://docs.supersalud.gov.co/PortalWeb/Juridica/Leyes/L0100_93.pdf.
https://docs.supersalud.gov.co/PortalWeb... . In theory, the special and contributory regimes offer the best access to healthcare, but in practice the special/exceptional regimes have shown some problems that could worsen the conditions of their affiliates compared to those of the contributory regime ²⁰20. Santiago Valenzuela. Buscan remedio a modelo de salud de los maestros [Internet]. El Colombiano; 2017 [citado el 15 de abril de 2020]. Disponible en: http://m.elcolombiano.com/buscan-remedio-a-modelo-de-salud-de-los-maestros-YK5837122.
http://m.elcolombiano.com/buscan-remedio... ^,2121. Redacción El Tiempo. Revolcón en el modelo de salud de las FFMM y de Policía [Internet]. El Tiempo; 2016 [citado el 15 de abril de 2020]. Disponible en: https://www.eltiempo.com/archivo/documento/CMS-16485772.
https://www.eltiempo.com/archivo/documen... . Recent laws from 2011 ²²22. Congreso de la República (Colombia). Ley de reforma al Sistema General de Seguridad Social en Salud. Ley 1438 de 2011. Diario Oficial No 47.957 del 19 de enero de 2011 [Internet]. Bogotá, Colombia; 2011 [citado el 15 de abril de 2020]. Disponible en: https://www.minsalud.gov.co/Normatividad_Nuevo/LEY%201438%20DE%202011.pdf.
https://www.minsalud.gov.co/Normatividad... and 2015 ²³23. Congreso de la República (Colombia). Ley Estatutaria de Salud. Ley No. 1751 de 2015. Diario Oficial No 49.427 de febrero 16 de 2015 [Internet]. Bogotá, Colombia; 2015 [citado el 13 de abril de 2020]. Disponible en: http://extwprlegs1.fao.org/docs/pdf/col145154.pdf.
http://extwprlegs1.fao.org/docs/pdf/col1... have advocated for universal healthcare access without socioeconomic differences. However, these legislative changes have not been fully implemented, and patients diagnosed before 2010 may have experienced different survival rates depending on their health insurance regime and their socioeconomic position.

Statistical analysis

The analyses were carried out using Microsoft Excel and Stata 14.2 (Stata Corporation, College Station, Texas, USA). Central and dispersion measures and relative frequencies for categorical variables were used in the univariate analysis. Incident case distributions by histological type and clinical staging are presented. In the bivariate analysis, the Kruskal-Wallis test was used to compare the distribution of the clinical stage according to health insurance and socioeconomic level. Survival results are presented using Kaplan-Meier curves. The Mantel-Haenzel log-rank test was used to compare survival estimates according to independent variables.

In addition, three multivariate Cox regression models were adjusted for both the health insurance regimen and socioeconomic level: i) a univariate (null) model; ii) a multivariate A model with age, histological subtype and clinical stage as covariates; and iii) a B model containing all the variables of model A plus an additional term to adjust the effect of the health insurance regimen according to socioeconomic level and, vice versa, the effect of socioeconomic level according to health insurance regimen for survival.

Ethical aspects

Confidentiality policies were respected to protect the sensitive information of the Population Cancer Registry of Manizales. The research has been authorized by the Research Ethics Committee of the Faculty of Health Sciences of the University of Caldas, and was classified as a minimum risk study according to Colombian legislation in force (Resolution 8430 of 1993 of the Ministry of Health).

RESULTS

Incidence

We found 217 incident cases in the study period. The mean age at diagnosis was 53.2 years (min.: 24 years; max.: 98 years). The percentage of cases with microscopic verification (alteration in the cytological smear + biopsy specimen histology) was 79.0%, a figure adjusted to the recommendations of the IARC ¹⁰10. Arias-Ortiz N, López-Guarnizo G. Evaluación de Calidad de los Datos del Registro Poblacional de Cáncer de Manizales, Colombia. Revista Colombiana de Cancerología. 2013;17(4):132-141.^,2424. Bray F, Parkin DM. Evaluation of data quality in the cancer registry: principles and methods. Part I: comparability, validity and timeliness. Eur J Cancer. 2009;45(5):747-55. doi: 10.1016/j.ejca.2008.11.032.
https://doi.org/10.1016/j.ejca.2008.11.0... . The predominant histological type was squamous cell carcinoma (Figure 1).

Regarding clinical stage at the time of diagnosis, stages I and II were observed in 46.1% of the population; stages III and IV in 53.9%; no stage information was found in 25% of the cases due to the lack of clinical records on tumor size, nodal involvement, and metastasis. From the total of patients, 95% had health insurance at the time of diagnosis; and the middle socioeconomic stratum predominated. The distribution of cases by health insurance scheme and socioeconomic level is presented in Table 1. The clinical stage at the time of diagnosis was analyzed according to the categories of socioeconomic level and a significant difference was found between the low and medium-high socioeconomic level. No differences were found in clinical stage according to health insurance regimen.

The average incidence rate for the 5-year period of 2008-2012 was 17.8 new cases per 100,000 women-years; 2.4% lower than that observed for the period of 2003-2007 and equivalent to an annual percentage change of -2.2%. By calendar year, there was a decrease in annual incidence (age-adjusted rate, all histological types) from 17.0 to 13.2 new cases per 100,000 woman-years between 2008 and 2012. Figure 2 shows the behavior of the annual incidence by histological type.

Survival

At the end of follow-up, 129 patients were alive and 88 were deceased, 63 died from cervical cancer before 60 months. There were 15 deaths from causes other than cervical cancer and 7 of those were found in death certificates; the percentage of follow-up losses was 3.2% (n = 7 cases). Survival estimates at 1, 3 and 5 years are presented in Table 1. Adenocarcinoma (histological type), early stage diagnosis and age under 70 years were variables associated with higher survival (Table 1).

In the multivariate analysis (Table 2), the risk of dying from cervical cancer up to 60 months after diagnosis was 90% higher in patients with undifferentiated or unspecified histological type compared to squamous cell carcinoma. Depending on the clinical stage, the risk increases three times for stage III and seven times for stage IV in contrast to stage I (Figure 3).

DISCUSSION

The mean age at the time of diagnosis found in this study is slightly lower than the one reported in Europe (53 vs. 56 years, respectively) and higher than the one reported in the Caribbean countries (48 years) ¹1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD 3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based regis tries in 71 countries. Lancet. 2018;391(10125):1023-75. doi: 10.1016/S0140-6736(17)33326-3.
https://doi.org/10.1016/S0140-6736(17)33... ^,22. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
https://doi.org/10.3322/caac.21492.... ^,2525. Pretorius R, Semrad N, Watring W, Fotheringham N. Presentation of cervical cancer. Gynecol Oncol. 1991;42(1):48-53. doi: 10.1016/0090-8258(91)90229-x.
https://doi.org/10.1016/0090-8258(91)902... .

The distribution by histological type was similar to that documented in the literature, in descending order of frequency: squamous cell, adenocarcinoma, and others. According to the World Health Organization, the most frequent histological type worldwide is the squamous cell, which represents 70-80% of cases, followed by adenocarcinoma, and other histological types with 10-15% each ¹²12. Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Cervical cancer, version 3. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001.
https://doi.org/10.6004/jnccn.2019.0001... . In accordance with world literature, undifferentiated, poorly differentiated, or rare histological subtypes have a worse prognosis and are generally observed in patients over 70 years old, while common histological variants present in younger patients with better survival ¹²12. Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Cervical cancer, version 3. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001.
https://doi.org/10.6004/jnccn.2019.0001... .

From the total cases, 53.9% were diagnosed in advanced stages (III and IV). Globally, advanced stages continue to be very high, especially in third world countries such as sub-Saharan Africa with 64% of new cases in stage III-IV. In the Americas, except for North America, Cuba, Chile and Uruguay, advanced stages represent 48% ¹1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD 3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based regis tries in 71 countries. Lancet. 2018;391(10125):1023-75. doi: 10.1016/S0140-6736(17)33326-3.
https://doi.org/10.1016/S0140-6736(17)33... ^,22. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
https://doi.org/10.3322/caac.21492.... . In a previous study in Manizales, it was reported that 54.7% of the new cases of cervical cancer corresponded to stages I and II⁹9. Arias Ortiz NE, De Vries E. Health inequities in cancer survival in Manizales, Colombia: a population-based study. Colomb Med. 2018;49(1):63-72. doi: 10.25100/cm.v49i1.3629.
https://doi.org/10.25100/cm.v49i1.3629... , results similar to the ones presented now. The difference in the clinical stage distribution according to the socioeconomic level denotes the known close relationship between poverty and the possibility of finding advanced disease, which indirectly influences the survival in this subset of patients ¹⁶16. Booth CM, Li G, Zhang-Salomons J, Mackillop WJ. The impact of socioeconomic status on stage of cancer at diagnosis and survival: A population-based study in Ontario, Canada. Cancer. 2010;116(17):4160-7. doi: 10.1002/cncr.25427.
https://doi.org/10.1002/cncr.25427... .

The age-adjusted incidence rates for histological types showed stable behavior, with minimal variations, with no statistically significant differences from previous periods ⁷7. Bravo LE, Arboleda OI, Ramirez O, Durán A, Lesmes MC, Rendler-García M, et al. Editorial. Cali, Colombia, C/Can 2025 aprendizaje clave: desafío de ciudades contra el cáncer. Colomb Med. 2017;48(2):39-40.^,1111. Tyczynski J, Demaret E, Parkin D. Standards and Guidelines for Cancer Registration in Europe [Internet]. IARC; 2003 [citado el 15 de febrero de 2019]. Disponible en: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Technical-Publications/Standards-And-Guidelines-For-Cancer-Registration-In-Europe-2003.
https://publications.iarc.fr/Book-And-Re... . Compared to the global scenario (GLOBOCAN 2018), the incidence rate in Manizales (17.8 per 100,000) is slightly higher than the world average of 14.0 per 100,000 inhabitants ²2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
https://doi.org/10.3322/caac.21492.... , but lower than that reported by the African continent. In the Colombian scenario, the incidence in Manizales is higher than that reported in cities such as Bucaramanga (13.0 per 100,000) ⁸8. Uribe CJ, Serrano SE, Hormiga CM. Incidencia y mortalidad por cáncer en Bucaramanga, Colombia. 2008-2012. Colomb Med. 2018;49(1):73-80. and Cali (15.3 per 100,000) ⁷7. Bravo LE, Arboleda OI, Ramirez O, Durán A, Lesmes MC, Rendler-García M, et al. Editorial. Cali, Colombia, C/Can 2025 aprendizaje clave: desafío de ciudades contra el cáncer. Colomb Med. 2017;48(2):39-40., similar to that observed in Pasto (18.0 per 100,000) ⁶6. Yepez MC, Jurado DM, Bravo LM, Bravo LE. Trends in cancer incidence and mortality in Pasto, Colombia. 15 years experience. Colomb Med. 2018;49(1):42-54. doi: 10.25100/cm.v49i1.3616.
https://doi.org/10.25100/cm.v49i1.3616... , and lower than that of Barranquilla (26.6 per 100,000) ⁵5. Moranth RV, Navarro E. Cancer incidence and mortality in Barranquilla, Colombia. 2008-2012. Colomb Med. 2018;49(1):55-62. doi: 10.25100/cm.v49i1.3627.
https://doi.org/10.25100/cm.v49i1.3627... .

The global 5-year survival rate reported in this research (68.9%) corresponds to the group of countries with intermediate-high performance in the CONCORD 3 study, which includes several developed countries in Europe and Asia. According to the mentioned study, the survival of patients with cervical cancer ranges from 50 to 70% in Central and South America and in several countries of Asia and Europe, while it is 70% or more in Japan, Korea, Taiwan, Denmark, Norway, Switzerland and Cuba. Countries such as Canada, United States, Brazil, Puerto Rico, China, Hong Kong, Singapore, Israel, Turkey, Australia, New Zealand and 18 countries in Europe, have survival rates between 60 and 69%¹1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD 3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based regis tries in 71 countries. Lancet. 2018;391(10125):1023-75. doi: 10.1016/S0140-6736(17)33326-3.
https://doi.org/10.1016/S0140-6736(17)33... .

In the Colombian context, data from the National Institute of Cancerology (INC), a national referral hospital, indicate that the probability of global survival at 2 years for this cancer was 62.3% ²⁶26. Pardo C, de Vries E. Breast and cervical cancer survival at Instituto Nacional de Cancerología, Colombia. Colomb Med. 2018;49(1):102-108. doi: 10.25100/cm.v49i1.284.
https://doi.org/10.25100/cm.v49i1.284... . This figure is lower than the 74% survival at 36 months reported in this study, a difference that could be explained by the complexity of cases that attend the INC as a national reference entity.

Survival was 51.4% in a previous (2003-2007) cohort of incident cases in Manizales, with a higher probability of survival in women in the contributory social security regime, compared to women in the subsidized regime and special or exceptional regimes ⁹9. Arias Ortiz NE, De Vries E. Health inequities in cancer survival in Manizales, Colombia: a population-based study. Colomb Med. 2018;49(1):63-72. doi: 10.25100/cm.v49i1.3629.
https://doi.org/10.25100/cm.v49i1.3629... . Results in this new cohort indicate an increase of more than 15% in survival and that could be due to improvements in the quality of care or better access to timely treatment for women living in the city.

In this study, the most influential factor for survival was the clinical stage at the time of diagnosis, with a significant proportion of cases in advanced stages, which indicates that, despite the improvement in overall survival, there are clear possibilities for progress in early detection that will continue to improve health outcomes. Other factors such as tumor histological type and age of diagnosis were adjusted to what is described in the international literature ¹²12. Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Cervical cancer, version 3. J Natl Compr Canc Netw. 2019;17(1):64-84. doi: 10.6004/jnccn.2019.0001.
https://doi.org/10.6004/jnccn.2019.0001... .

One of the strengths of this study is that it was carried out from data of the Population Cancer Registry of the city of Manizales, which complies with the data quality standards of the international agencies specialized in the matter.

This study achieves important progress by providing a complete data report for clinical staging in comparison with the previous study, which ratifies the importance of data use from the country’s population cancer registries. The greater the magnitude of data used, the greater the efforts invested in improving its quality. Punctually, progress was made from 42% to 75% of cases with valid and complete information for this variable ⁹9. Arias Ortiz NE, De Vries E. Health inequities in cancer survival in Manizales, Colombia: a population-based study. Colomb Med. 2018;49(1):63-72. doi: 10.25100/cm.v49i1.3629.
https://doi.org/10.25100/cm.v49i1.3629... . In addition, a decade of incident cases (2003-2012) has been followed up, allowing the system performance to be evaluated based on the baseline defined in the first 5-year period. These results can also be extrapolated to other intermediate Andean cities in Colombia, with which Manizales shares some sociodemographic and healthcare system characteristics.

There were some limitations to the study such as the fact that it was not possible to complete the follow-up of all patients, although the percentage of losses was less than 10%, which is usually accepted in this type of study. In addition, there were difficulties to find complete data for some variables such as those related to socioeconomic position. Nevertheless, in the descriptive analyses, the categories “unknown” or “no data” were preserved, in order not to lose the intended exhaustiveness in the studies with population data. Thus, in the case of staging, for example, the category “unknown” is informative of the proportion of cases that did not reach the staging, which can be due to barriers regarding healthcare access and the quality of the clinical records. For some variables, the number of cases and the number of events was insufficient to obtain stable estimates, which forced the regrouping of categories with the consequent loss of information.

In conclusion, the incidence of cervical cancer in Manizales is similar to global rates and places the city close to the global average; in Latin America, Manizales is in the group with the best rates. In the national scenario, the incidence is intermediate compared with other cities where there is a population-based register. The favorable change in the survival of cervical cancer in Manizales could be evidenced, going from 52% to 69%. Likewise, in the multivariate analysis no significant differences were observed in the survival according to socioeconomic level, but advanced stages were observed in women of medium and low socioeconomic levels.

Acknowledgements

To the Territorial Directorate of Health of the Department of Caldas, to the sources of information of the Population Cancer Registry of Manizales (RPC-M) for their contribution to the study follow-up, and to the staff of the RPC-M for their dedication in obtaining the data.

References

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