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In 2023, the manufacturing of all the ITER TF coils has been completed 15 years after the sign of procurement arrangements in 2008. This paper has been jointly submitted by F4E and QST to recollect the lessons learnt in the production of the two parties along the last 15 years.

FUNDAMENTO: Estudio descriptivo del cáncer invasor de cérvix en el Area Sanitaria de Girona, a partir de los datos del Registro Poblacional de Cáncer. MÉTODOS: El estudio comprende el período de 1980 a 1989 y la población observada incluye a las mujeres residentes en el Area Sanitaria. Se ha realizado el cálculo de tasas de incidencia bruta, ajustada, truncada y acumulada, así como un análisis de tendencia, de distribución demográfica del tumor y un análisis de la supervivencia poblacional. RESULTADOS: La edad media de presentación del cáncer fue de 57"14 años; el tipo histológico más frecuente el carcinoma escamoso; el 51% de los casos son mujeres nacidas en Cataluña, el resto son inmigrantes y extranjeras. La distribución de estadíos en el momento del diagnóstico fue: 36% casos locales, 34% regionales y 23% diseminados. Las tasas bruta, ajustada y truncada de incidencia en el período 1980-89 eran de 8.2, 6.2 y 13.7 casos x105 mujeres respectivamente. Según la tasa acumulada, una de cada 150 mujeres sufrirán este tumor antes de los 75 años. No se observa un incremento significativo de la tendencia; por el contrario, se aprecia una subincidencia significativa en zonas rurales. La probabilidad de supervivencia relativa a los 5 años es del 48.5%, no apreciándose diferencias significativas en función de la edad pero sí en función del estadío. CONCLUSIONES: En comparación con las cifras internacionales, Girona es un área de baja incidencia de este tumor, no observándose una tendencia ascendente del mismo. La subincidencia en zonas rurales puede sugerir una diferente exposición a factores de riesgo, aunque hay que tener en cuenta aspectos como la accesibilidad a los servicios sanitarios, la definición de medio urbano y rural, y la presencia de movimientos migratorios. Por último, la menor supervivencia observada en comparación con otros países podría atribuirse a la presencia de estadíos más avanzados, lo que pone de relieve la importancia de la detección precoz de este tumor.

Background: the effects and costs of different policies for breast cancer screening in Catalonia (Spain) were analysed, to give a basis for setting priorities and deciding on the introduction of a screening programme. Methods: the MISCAN (MIcrosimulation SCreening ANalysis) model of the natural history of breast cancer was used. The epidemiology of breast cancer in Catalonia and the demography of the Catalan population was taken into account as well as the results on mortality reduction from a Swedish overview of breast cancer screening trials. Results: the reduction in breast cancer mortality in the total female population due to a screening programme for the age group 50-64 years would be 16, 12 and 9%, with screening intervals of one, two and three years respectively. The cost-effectiveness ratios (CE ratios) for these scenarios were 924,000, 730,000 and 719,000 pesetas (PO per life-year gained respectively (5% discounting). The most cost-effective screening scenario is the one in which women aged 50-69 years are screened with an interval of three years with a mortality reduction of approximately 12% in the total female population (CE ratio = 694,000 Pt). Screening until the age of 69 years (two year interval) was almost as cost-effective as screening the age group 50-64 years with a two year interval, with a reduction in breast cancer mortality of 15%. Extension to under the age of 50 years resulted in diverging results depending on the assumptions for improvement in prognosis for younger women (40-49 years). Conclusion: if the extension of a two yearly screening programme for women aged 50-64 years is considered (mortality reduction of 12%), extension to older women would be more advisable, based on proven benefits and costs, than extension to younger age groups. [ABSTRACT FROM AUTHOR]

Our aim was to estimate the prevalence of mutations in the BRCA1 and BRCA2 genes among unselected incident cases of breast cancer in young women. We identified 158 incident breast cancer cases diagnosed before age 46 years in predefined geographic areas in Girona and Tarragona, Spain, during 1995-1997. Of these, 136 (86%) provided information on family history of cancer and were screened for BRCA1 and BRCA2 mutations. Nine of the 136 (6.6%) were found to carry BRCA deleterious mutations (MUT) (1 BRCA1 and 8 BRCA2), and 20 were detected with rare BRCA variants of unknown significance (UV). Both MUT and US BRCA alterations were more frequent in younger patients: 7 (11.6%) MUT and 12 (19.3%) UV carriers were found in the group of 62 patients younger than 40 years, whereas 2 (2.7%) MUT and 9 (12%) US carriers were identified in the group of 74 patients aged 40-45. Family history of breast and ovarian cancers suggestive of hereditary condition (at least 2 first- or second-degree relatives affected with breast cancer or at least 1 relative affected with ovarian cancer or early-onset breast cancer) was absent for 5 of 9 MUT carriers. This suggests that BRCA screening policies based on family history of cancer would miss a considerable proportion of BRCA mutations. Mutations in the BRCA1 and BRCA2 genes explain at least 10% of breast cancer cases diagnosed before age 40 years. The contribution of these genes to early-onset breast cancer is likely to be even higher given that certain UV cases might be disease-associated., (Copyright 2003 Wiley-Liss, Inc.)

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Background: To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer., Patients and Methods: From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption., Results: 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer., Conclusions: First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.

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.

Background: To evaluate the risk of developing breast cancer among Catalan women and to estimate the number of new cases of this tumor that appear annually in Catalonia (north-east of Spain)., Material and Methods: The incidence rates of breast cancer were used in the period 1985-1989 proceeding from the population-based cancer registries of Tarragona and Girona. The age-specific rates (ASR) in Catalonia were estimated by an ASR average of Girona and Tarragona, that were adjusted by the standardized mortality ratio (SMR) of these health regions in relation to Catalonia. The cumulative rate and the risk of developing breast cancer were calculated, considering the probability of death by other causes. The temporal trend of breast cancer incidence was analysed by the Poisson's regression model., Results: The cumulative risk (0-74 years) for breast cancer among Catalan women was 5.17% (1 out of 19 women). The highest risk of developing breast cancer is in the group of age between 60 and 79 years old. Tarragona and Girona had both a moderate increase that was not statistically significant. About 2,550 new cases of breast cancer have been estimated in 1994 and 2,600 in 1996., Conclusion: The risk of developing breast cancer in Catalonia after adjusting for the probability of dying by other causes, is lower than in other countries of Northern Europe and the United States.

Background: It is now established that certain types of human papillomaviruses (HPVs) are the sexually transmitted agents etiologically linked to cervical cancer. Studies assessing the contribution of the male's sexual behavior and genital HPV DNA status to the risk of development of cervical neoplasia in sexual partners have yielded inconsistent results., Purpose: This study evaluates the role of men's sexual behavior and the presence of HPV DNA in the penis on the development of cervical cancer in their sexual partners in Spain, a low-risk area for cervical neoplasia., Methods: Husbands (n = 633) of women participating in two case-control studies of cervical neoplasia were interviewed to obtain information on lifestyle habits, including sexual practices. Cytologic samples were taken from the distal urethra and the surface of the glans penis of 183 husbands of case women and of 171 husbands of control women. These samples were analyzed by a polymerase chain reaction-based system using a generic probe and 25 type-specific probes for the detection and typing of HPV DNA. Serologic specimens were also obtained and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae., Results: The presence of HPV DNA in the husbands' penis conveyed a fivefold risk of cervical cancer to their wives (adjusted odds ratio [OR] for HPV DNA positivity = 4.9; 95% confidence interval [CI] = 1.9-12.6). The risk of cervical cancer was strongly related to HPV type (adjusted OR for HPV type 16 = 9.0; 95% CI = 1.1-77.5), to the husbands' number of extramarital partners (adjusted OR = 11.0; 95% CI = 3.0-40.0; for > or = 21 women versus one), and to the number of prostitutes as extramarital sexual partners (adjusted OR = 8.0; 95% CI = 2.9-22.2; for > or = 10 women versus none). Presence of antibodies to C. trachomatis (adjusted OR = 2.6; 95% CI = 1.4-4.6) and an early age at first sexual intercourse of the husband (adjusted OR = 3.2; 95% CI = 1.7-5.9; for < or = 15 years versus > or = 21 years) were also associated with cervical neoplasia in the wife. After adjustment for these variables and for the wife's pack-years of smoking, the husband's smoking was moderately associated with cervical cancer in his wife (adjusted OR = 2.5; 95% CI = 1.4-4.4; for > or = 26.2 pack-years versus none)., Conclusions: The study supports the role of men as vectors of the HPV types that are related to cervical cancer. Life-time number of female sexual partners, number of female prostitutes as sexual partners, and detection of HPV DNA in the penis of husbands are all surrogate markers of exposure to HPV during marriage., Implications: Men who report multiple sexual partners or who are carriers of HPV DNA may be vectors of high-risk HPV types and may place their wives at high risk of developing cervical cancer. Prostitutes are an important reservoir of high-risk HPVs.

Background: To analyze the perception of causes and prevention of cancer among women, from Girona, Spain, as well as to assess the knowledge of initial symptoms and participation in cancer screening activities., Subjects and Methods: Crossectional survey with the following items: cancer risk factors, initial symptoms, perceived susceptibility, knowledge and practice of screening, beliefs regarding prevention and treatment of cancer, intention to attend screening tests and socio-demographic variables. A stratified random sample of 408 women aged 40 to 70 from two counties in Girona, Spain was selected., Results: More than 80% of women identified tobacco, radioactivity and other environmental factors as causes of cancer, being the alcohol identified by 70% of women. It was clearly observed that a high level of these women (97.5%) considered a lump in the breast as an initial symptom of cancer, whereas only a 6.6% thought it was always due to cancer. With regard to cancer screening, 21.9% of women have ever practiced a mammography, 28.5% a cervical citology with Papanicolaou staining and 53.2% self-breast examinations. All these screening activities were inversely associated to age (p < 0.05) and directly to educational level (p < 0.05)., Conclusion: A high knowledge regarding the causes of cancer with the exception of diet was observed in women from Girona, Spain. Knowledge and participation in screening activities is still low in practice of population cancer screening programmes.

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.