Cumplimiento de las recomendaciones dietéticas vigentes y variabilidad geográfica de la dieta en mujeres participantes en 7 programas de cribado de cáncer de mama en España / Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain

Introducción: Una dieta saludable es especialmente importante durante la menopausia, periodo en el que aumenta el riesgo de varios problemas de salud. Analizamos la dieta de mujeres peri y postmenopáusicas españolas y el grado de cumplimiento de las recomendaciones actuales. Material y métodos: Estudio transversal en 3.574 mujeres de 45-68 años que acuden al cribado de cáncer de mama en 7 centros (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia y Zaragoza). Se recogió la dieta mediante un cuestionario de frecuencia de alimentos validado para población española. Para la valoración del cumplimiento de las recomendaciones actuales se utilizaron los rangos recomendados por la Sociedad Española de Nutrición Comunitaria para ingesta de grupos de alimentos y las Ingestas Diarias Recomendadas (IDR) para energía, vitaminas y minerales de la Federación Española de Nutrición, Alimentación y Dietética. Resultados: El 29% de las mujeres eran obesas y un 42% tenía sobrepeso. El aporte calórico medio fue de 2.053 kcal (DE: 480). El perfil calórico general fue de: 43% de la energía aportada por lo carbohidratos, 36% por las grasas, 20% por las proteínas. Se evidenció una ingesta deficiente de vitamina D en todos los nodos del estudio, con una ingesta media general de 2,14 μg/día. Se detectó a su vez una ingesta deficitaria de vitamina E en A Coruña y Burgos. Todos los centros presentaron una ingesta elevada de productos lácteos y de legumbres. El consumo de frutas y verduras fue muy heterogéneo siendo especialmente elevada su ingesta en Mallorca y Valencia mientras que fue baja para ambos grupos de alimentos en A Coruña. La ingesta de aceite de oliva fue elevada en todos los centros exceptuando Burgos con un 74,3% de las mujeres estudiadas por debajo de las 3 raciones al día recomendadas. Conclusiones: Una dieta con menos grasas y proteínas y más rica en vegetales, frutos secos y alimentos ricos en hidratos de carbono equilibraría el balance energético y mejoraría la calidad de la dieta corrigiendo las bajas ingestas de vitaminas D y E. Estas recomendaciones son especialmente importantes en las ciudades más alejadas de la costa mediterránea donde se han detectado mayores incumplimientos de las recomendaciones vigentes y una dieta más alejada de la dieta mediterránea (AU)

Introduction: A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. Material and methods: We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. Results: The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. Conclusions: A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet (AU)

[Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain]. / Cumplimiento de las recomendaciones dietéticas vigentes y variabilidad geográfica de la dieta en mujeres participantes en 7 programas de cribado de cáncer de mama en España.

INTRODUCTION: A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. MATERIAL AND METHODS: We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. RESULTS: The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. CONCLUSIONS: A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet.

On the modelling of biological patterns with mechanochemical models: Insights from analysis and computation.

The diversity of biological form is generated by a relatively small number of underlying mechanisms. Consequently, mathematical and computational modelling can, and does, provide insight into how cellular level interactions ultimately give rise to higher level structure. Given cells respond to mechanical stimuli, it is therefore important to consider the effects of these responses within biological self-organisation models. Here, we consider the self-organisation properties of a mechanochemical model previously developed by three of the authors in Acta Biomater. 4, 613-621 (2008), which is capable of reproducing the behaviour of a population of cells cultured on an elastic substrate in response to a variety of stimuli. In particular, we examine the conditions under which stable spatial patterns can emerge with this model, focusing on the influence of mechanical stimuli and the interplay of non-local phenomena. To this end, we have performed a linear stability analysis and numerical simulations based on a mixed finite element formulation, which have allowed us to study the dynamical behaviour of the system in terms of the qualitative shape of the dispersion relation. We show that the consideration of mechanotaxis, namely changes in migration speeds and directions in response to mechanical stimuli alters the conditions for pattern formation in a singular manner. Furthermore without non-local effects, responses to mechanical stimuli are observed to result in dispersion relations with positive growth rates at arbitrarily large wavenumbers, in turn yielding heterogeneity at the cellular level in model predictions. This highlights the sensitivity and necessity of non-local effects in mechanically influenced biological pattern formation models and the ultimate failure of the continuum approximation in their absence.

Computational simulation of dental implant osseointegration through resonance frequency analysis.

The aim of this study is to predict the evolution of the resonance frequency of the bone-implant interface in a dental implant by means of finite element simulation. A phenomenological interface model able to simulate the mechanical effects of the osseointegration process at the bone-implant interface is applied and compared with some experimental results in rabbits. An early stage of slow bone ingrowth, followed by a faster osseointegration phase until final stability is predicted by the simulations. The evolution of the resonance frequency of the implant and surrounding tissues along the simulation period was also obtained, observing a 3-fold increase in the first principal frequency. These findings are in quantitative agreement with the experimental measurements and suggest that the model can be useful to evaluate the influence of mechanical factors such as implant geometry or implant loading on the indirect evaluation of the process of implant osseintegration.

A damage model for the growth plate: application to the prediction of slipped capital epiphysis.

Despite slipped capital femoral epiphysis (SCFE) being one of the most common disorders of the adolescent hip, its early diagnosis is quite difficult. The main objective of this work is to apply an interface damage model to predict the failure of the bone-growth plate-bone interface. This model allows to evaluate the risk of development of SCFE and to investigate the range of mechanical properties of the physis that may cause slippage of the plate. This paper also studies the influence of different geometrical parameters and body weight of the patient on the development of SCFE. We have demonstrated, thanks to the proposed model, that higher physeal sloping and posterior sloping angles are associated to a higher probability of development of SCFE. In a similar way, increasing body weight results in a more probable slippage.

[Time trends in cancer incidence in Navarra and Zaragoza, spain]. / Tendencia temporal de la incidencia de cáncer en Navarra y Zaragoza.

BACKGROUND AND OBJECTIVES: The knowledge of time-related changes occurring in cancer incidence and mortality is an essential element for cancer control. This paper aims to describe the time trends of the more important cancer sites in Navarra and Zaragoza. METHODS: The influence of age, diagnosis period and birth cohort on the observed time trend cancer incidence in Navarre and Zaragoza was assessed using a log-linear model. Results are showed graphically, for the different tumour sites by sex and each registry. RESULTS: Among males, a considerable rise in the incidence of lung cancer (5% per year), prostate cancer (> 2% per year) and non-Hodgkin's lymphomas was found. Among females, the highest increases corresponded to non-Hodgkin's lymphomas, with a yearly rise greater than 7%, and ovarian cancer (4% per year). Breast cancer in women increased in both registries (3.5% per year in Navarre and 0.9% per year in Zaragoza), part of the increment in Navarra being explained by a higher case detection rate. Finally, the incidence of colorectal, bladder and kidney cancer rose more than a 3% per year in both registries and sexes. For most types of tumours, cancer risk increased with subsequent generations. CONCLUSION: The substantial cancer increment observed points out the inefficacy of primary prevention policies, the importance of studying cancer incidence for long time periods and the need to increase the population coverage of Spanish cancer registries.

Tendencia temporal de la incidencia de cáncer en Navarra y Zaragoza / Time trends in cancer incidence in Navarra and Zaragoza, Spain

Objetivo: Conocer los cambios que se producen en los patrones de incidencia y mortalidad por cáncer con el paso del tiempo es un elemento básico para su control. En este trabajo se presentan los resultados sobre la evolución temporal de la incidencia de los tumores más importantes en Navarra y Zaragoza. Métodos: Se ha utilizado un modelo log-lineal para evaluar el efecto de la edad, el período de diagnóstico y la cohorte de nacimiento en las tendencias de la incidencia de cáncer empleando los datos de los registros de Navarra y Zaragoza. Los resultados se muestran en forma gráfica para los diferentes tumores, en cada registro y sexo. Resultados: En hombres, destaca el fuerte aumento de la incidencia en cáncer de pulmón (5 por ciento anual), próstata (> 2 por ciento anual) y linfomas no hodgkinianos. En mujeres, los incrementos más altos se han producido en linfomas no hodgkinianos con aumentos superiores al 7 por ciento anual y en el cáncer de ovario (4 por ciento anual). El cáncer de mama en mujeres ha aumentado en ambas provincias (Navarra 3,5 por ciento y Zaragoza 0,9 por ciento), siendo una parte del incremento en Navarra derivado de una mayor detección de casos. En ambos registros y en los dos sexos se han producido incrementos de la incidencia superiores al 3 por ciento anual en cáncer colorrectal, de vejiga y de riñón. Para la mayor parte de los tumores el riesgo de padecer un cáncer se incrementa en las sucesivas generaciones, con la excepción del cáncer de estómago y del cáncer de hígado. Conclusiones: El importante incremento de la incidencia de cáncer pone de manifiesto la insuficiencia de las políticas de prevención primaria, la importancia de disponer de datos de incidencia en series prolongadas en el tiempo y la necesidad de aumentar la cobertura poblacional de los registros de cáncer en España (AU)

Brain cancer incidence in the provinces of Zaragoza and Navarre (Spain): effect of age, period and birth cohort.

Several studies have detected increases in malignant brain tumour incidence and mortality rates particularly among the elderly. We analyzed time trends in malignant brain tumors incidence in Zaragoza over the period 1973-1990 and Navarre over the period 1973-1991, two Spanish provinces that have been collecting data through their respective Cancer Registries for the last 20 years, using Poisson regression analysis of age, period of diagnosis and cohort. In general, age-adjusted rates showed a steady rise in both registries, except in the case of females in Navarre, for whom a decrease in risk was observed for the last period, 1988-1991. This increase is a reflection of the rise in incidence experienced by the elderly, since the cohorts successively register rates that are stable over time, and even downward in the case of females in Navarre. The risk run by generations born circa 1920-1930 was the highest encountered. Rates were higher in Navarre in both sexes and for all but the last period in females, when rates on the two registers stood level. Increasingly generalised use of CT scanning and magnetic resonance in the 1980s in Spain, coupled with better and more effective health care access for the elderly, are factors that may well have some bearing on these findings.

Rising incidence of non-Hodgkin's lymphoma in Spain: analysis of period of diagnosis and cohort effects.

Incidence trends in non-Hodgkin's lymphomas for the period 1973-1991 were studied using data from Spain's Zaragoza and Navarre registries. The overall rate of increase was 5.8% per year. Age-period-cohort models were used, also including sex and registry as explanatory variables. In these models, the variable period was categorized according to the observed changes in diagnostic availability during the length of the study. Non-Hodgkin's lymphomas increased with age, and rates were 31% lower in women. Incidence was almost 50% higher in Navarre, but differences in registry procedures might account for this discrepancy. The rise affects all adult age groups and seems to be the result of changes related not only to the period of diagnosis, mainly ascribable to improvements in diagnostic and coding practices, but also to the birth cohort. According to the model, the risk increased with on-coming generations at a rate of 1.5% per year. The AIDS epidemic in Spain is unable to explain this trend, although it may well exert a stronger influence in the future. Additional knowledge is required to understand the observed rise and to prevent the growing numbers of cases that are expected in years to come.

Time trend and age-period-cohort effects on gastric cancer incidence in Zaragoza and Navarre, Spain.

STUDY OBJECTIVE: To describe time trends in gastric cancer incidence in Zaragoza and Navarre, and to investigate time period and birth cohort as determinants of such trends. DESIGN: Cases from two registries were grouped into five year intervals and the following were calculated: age specific and sex specific incidence rates, and the male to female ratio. Log linear models including age, period of diagnosis, and birth cohort were fitted. SETTING: The Zaragoza Cancer Registry covers the province of Zaragoza, which has a population of 824,776 (403,755 men and 421,021 women). The Navarre Cancer Registry covers the province of Navarre which has 512,512 inhabitants (254,786 men and 257,726 women). In both cases population figures were based on the late census. PATIENTS: These comprised incident cases of gastric cancer reported to the Zaragoza Cancer Registry in 1963-87 and to the Navarre Cancer Registry in 1973-87. MAIN RESULTS: Navarre registered higher adjusted and cumulative rates than Zaragoza for both sexes. In both provinces, there were relative declines in the rates for men and women of 3% and 4% respectively per year. In Zaragoza, the risk of developing stomach cancer fell in generations born between 1888 and 1933, and rose in subsequent birth cohorts in both sexes, while in Navarre the cohort effect showed an approximately linear risk for both sexes. Both provinces recorded increases in risk associated with cohorts born between 1933 and 1943. CONCLUSION: The incidence rates of gastric cancer fell in both Zaragoza and Navarre. The reason for the greater incidence of gastric cancer in Navarre remains unknown. Trends in rates seem to be mainly linked to birth cohort. Increases in risk in generations born after 1933 may be ascribable to nutritional deficiencies in the early years of life.

Childhood cancer incidence in Zaragoza and Navarre (Spain): 1973-1987.

Patterns and trends in childhood cancer incidence for Navarre and Zaragoza registries were studied over the 15-year period, 1973-1987. Overall cancer rates and rates for 10 specific types of cancer were analysed using a log-linear Poisson model or, alternatively, a gamma-Poisson model whenever overdispersion was present, with age, sex, registry and period being used as predictor variables. Childhood cancer was 30% more frequent in boys than in girls, and, except for lymphomas and bone tumours, incidence decreased remarkably with age. Adjusted rates were high in comparison with other European countries, particularly in the case of non-Hodgkin's lymphomas. Cancer rates proved somewhat higher in Navarre, but this difference attained statistical significance solely in the case of central nervous system tumours (rate ratio = 1.75; 95% confidence interval 1.21-2.54). A significant rise in overall incidence was observed (11% 5-yearly increase) due mainly to the upward trend in central nervous system tumours. While the rise in these tumours coincides with the period which witnessed the spread of computerised tomography in Spain, the trend nevertheless held steady over the last 5-year period, when access to this diagnostic technique had already become generalised nationwide.

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Age-period-cohort modeling of colorectal cancer incidence and mortality in Spain.

Spain registers a much lower rate of colorectal cancer incidence and mortality than do other European countries, yet the rises observed in the adjusted rates over recent decades led us to attempt to monitor the trends over time using Poisson log-linear models. Incidence data were furnished by the Zaragoza and Navarre population-based cancer registries, whereas mortality data corresponded to Spain as a whole. For trend evaluation purposes, we made use of invariant parameters from age-period-cohort models (net drift and curvature) and a restriction of the cohort-effect slope range. The results suggest the presence of a marked rise in incidence of colorectal cancer for both sexes and across all age groups in the provinces studied. The rise in mortality was less pronounced than the rise in incidence and seemed to coincide with a marked cohort effect present throughout the study period. Both in incidence and mortality, the increases were more pronounced among men. When studied jointly, incidence and mortality trends tend to be complementary, rendering an approach of this nature especially important in sites with better survival, such as the case in point.

Risk factors for HPV DNA detection in middle-aged women.

BACKGROUND AND OBJECTIVES: Strong epidemiologic evidence indicates that human papillomavirus (HPV) is the main etiologic factor of cervical cancer. A few cohort studies suggest that most HPV infections are transient in young women and that persistent HPV infections are more common in older women. Little is known about the determinants of persistent HPV infections. The present study was aimed at increasing our knowledge about these determinants. GOALS: To identify risk factors for genital HPV DNA detection among cytologically normal middle-aged women. STUDY DESIGN: Eight hundred ten women who participated as control subjects in three case-control studies on cervical cancer in Spain, Colombia, and Brazil were included in this study. After an interview, women underwent a gynecologic examination with collection of exfoliated cells for a Papanicolaou smear and HPV DNA detection. Human papilloma virus DNA was detected by polymerase chain reaction (PCR)-based hybridization techniques. RESULTS: The HPV positivity rate was 10.5% in the whole population, but was higher in the areas with high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than in Spain (4.9%), which is a low-risk area for cervical cancer. Age was related to the prevalence of HPV DNA in Brazil, but not in Spain and Colombia. In univariate analyses in all three countries, the prevalence of HPV DNA was positively associated with the number of lifetime sexual partners and inversely associated with the levels of family income and with age at first sexual intercourse. There was four times increase in the odds ratio (OR) of HPV infection in women who had six or more lifetime sexual partners compared with those with one or less. The use of any kind of contraceptive tended to decrease the OR for HPV detection. Their ORs ranged from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and Colombia, antibodies against Chlamydia trachomatis were positively associated with the prevalence of HPV DNA. In a final multivariate model, the positive associations with lifetime number of sexual partners, socioeconomic status, and C. trachomatis persisted. CONCLUSIONS: These results support the sexual transmission of HPV and suggest that socioeconomic status and antibodies to C. trachomatis are independent predictors of HPV detection in middle-aged cytologically normal women.

Serological response to HPV16 in CIN-III and cervical cancer patients. Case-control studies in Spain and Colombia.

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

[Human papilloma virus in the etiology of cervicouterine cancer]. / El virus del papiloma humano en la etiología del cáncer cervicouterino.

The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)

El virus del papiloma humano en la etiología del cancer cervicouterino / The human papilloma virus in the etiology of cervical cancer

Los objetivos del estudio fueron verificar la hipótesis según la cual el carcinoma invasor del cuello uterino y sus precursores son causados la mayor parte de las veces por infecciones debidas al virus del papiloma humano (VPH), y si otros factores de riesgo intervienen en el proceso neoplásico. Para ello, se realizaron cuatro estudios concurrentes de casos y controles. Dos de ellos incluyeron casos de carcinoma invasor y controles de base poblacional. Los dos restantes incluyeron casos y controles de carcinoma in situ. La investigación se realizó en nueve provincias de España y en Cali, Colombia. La identificación de casos tuvo lugar entre junio de 1985 y junio de 1988. Se incluyeron 436 casos incidentes de carcinoma invasor y 387 controles, seleccionados al azar de las poblaciones correspondientes, y 525 casos de carcinoma in situ y 512 controles apareados por edad, centro de reclutamiento y fecha de toma citológica entre mujeres participantes en programas de tamizaje citológico. La exposición al VPH se detectó mediante pruebas de hibridación tras amplificación por la reacción en cadena de la polimerasa en células cervicales exfoliadas de casos y controles. La exposición al VPH fue el factor de riesgo principal en los cuatro estudios

Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia.

A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.

El virus del papiloma humano en la etiología del cancer cervicouterino / The human papilloma virus in the etiology of cervical cancer

Los objetivos del estudio fueron verificar la hipótesis según la cual el carcinoma invasor del cuello uterino y sus precursores son causados la mayor parte de las veces por infecciones debidas al virus del papiloma humano (VPH), y si otros factores de riesgo intervienen en el proceso neoplásico. Para ello, se realizaron cuatro estudios concurrentes de casos y controles. Dos de ellos incluyeron casos de carcinoma invasor y controles de base poblacional. Los dos restantes incluyeron casos y controles de carcinoma in situ. La investigación se realizó en nueve provincias de España y en Cali, Colombia. La identificación de casos tuvo lugar entre junio de 1985 y junio de 1988. Se incluyeron 436 casos incidentes de carcinoma invasor y 387 controles, seleccionados al azar de las poblaciones correspondientes, y 525 casos de carcinoma in situ y 512 controles apareados por edad, centro de reclutamiento y fecha de toma citológica entre mujeres participantes en programas de tamizaje citológico. La exposición al VPH se detectó mediante pruebas de hibridación tras amplificación por la reacción en cadena de la polimerasa en células cervicales exfoliadas de casos y controles. La exposición al VPH fue el factor de riesgo principal en los cuatro estudios

Risk factors for cervical cancer in Colombia and Spain.

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.

PIP: Findings are presented from a population-based case-control study of cervical cancer conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behavior, the use of oral contraceptives, screening practices, and smoking. 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population which generated the cases participated in the study. Cases in Colombia were of mean age 46.5 years compared to 52.2 years in Spain. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the most significant risk factor, with at least 70% of cervical cancer cases associated with the viral infection. Risk estimates for other factors were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer, with patients with cervical cancer who were HPV DNA-negative retaining most of the established epidemiological features of the disease. This latter finding suggests that some cases of HPV infection were undetected or that other sexually transmitted factors contribute to the causation of cervical cancer. Early age at first intercourse and early age at first birth were independently associated with an increased risk of cervical cancer. Low educational level was a risk factor and the number of sex partners was a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening and ever having undergone a Caesarean section were protective factors.