Breast cancer detection risk in screening mammography after a false-positive result.

BACKGROUND: False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. METHODS: This is a retrospective cohort study of 762,506 women aged 45-69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. RESULTS: False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28-3.16 and OR = 1.81; 95%CI: 1.70-1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23-6.66). Other factors associated with an increased cancer detection risk were age 65-69 years (OR = 1.84; 95%CI: 1.67-2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11-1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13-1.35). CONCLUSION: Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Effect of protocol-related variables and women's characteristics on the cumulative false-positive risk in breast cancer screening.

BACKGROUND: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and women's characteristics affect the cumulative false-positive risk. METHODS: This is a retrospective cohort study of 1,565,364 women aged 45-69 years who underwent 4,739,498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. RESULTS: The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR)=2.06 and 4.44, respectively], two mammographic views (OR=0.77 and 1.56, respectively), digital mammography (OR=0.83 for invasive procedures), premenopausal status (OR=1.31 and 1.22, respectively), use of hormone replacement therapy (OR=1.03 and 0.84, respectively), previous invasive procedures (OR=1.52 and 2.00, respectively), and a familial history of breast cancer (OR=1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50-51 was 20.39% [95% confidence interval (CI) 20.02-20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66-1.87), ranging from 12.02% to 1.58%. CONCLUSIONS: The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs.

Effect of false-positives and women's characteristics on long-term adherence to breast cancer screening.

False-positive results may influence adherence to mammography screening. The effectiveness of breast cancer screening is closely related to adequate adherence among the target population. The objective of this study was to evaluate how false-positives and women's characteristics affect the likelihood of reattendance at routine breast cancer screening in a sequence of routine screening invitations. We performed a retrospective cohort study of 1,371,218 women aged 45-69 years, eligible for the next routine screening, who underwent 4,545,346 screening mammograms from 1990 to 2006. We estimated the likelihood of attendance at seven sequential screening mammograms. Multilevel discrete time hazard models were used to estimate the effect of false-positive results on reattendance, and the odds ratios (OR) of non-attendance for the women's personal characteristics studied. The overall reattendance rate at the second screening was 81.7% while at the seventh screening was 95.6%. At the second screening invitation reattendance among women with and without a false-positive mammogram was 79.3 vs. 85.3%, respectively. At the fourth and seventh screenings, these percentages were 86.3 vs. 89.9% and 94.6 vs. 96.0%, respectively. The study variables associated with a higher risk of failing to participate in subsequent screenings were oldest age (OR = 8.48; 95% CI: 8.31-8.65), not attending their first screening invitation (OR = 1.12; 95% CI: 1.11-1.14), and previous invasive procedures (OR = 1.09; 95% CI: 1.07-1.10). The risk of non-attendance was lower in women with a familial history of breast cancer (OR = 0.97; 95% CI: 0.96-0.99), and those using hormone replacement therapy (OR = 0.96; 95% CI: 0.94-0.97). In conclusion, reattendance was lower in women with false-positive mammograms than in those with negative results, although this difference decreased with the number of completed screening participations, suggesting that abnormal results in earlier screenings more strongly influence behavior. These findings may be useful in providing women with accurate information and in improving the effectiveness of screening programs.

Cancer screening in Spain.

OBJECTIVE: To describe the current status of breast, colorectal and cervical cancer screening in Spain. METHODOLOGY: The situation was analysed on the basis of data drawn from surveys conducted in each autonomous region (Comunidad Autónoma). RESULTS: Currently, breast cancer screening coverage is 100%. In 2007, overall participation was 67.0% with an adherence of 91.2%. The detection rate was 3.4 per thousand, 15.1% intraductal and 30% invasive <1 cm in diameter, with 65% showing axilary node negative. Colorectal cancer screening had been implemented in six regions (4.5% of the target population). Participation ranged from 17.2% to 42.3%, with positive test percentages ranging from 1.7 per thousand (guaiac) to 9.5% (immunological). The invasive cancer detection rate was 1.7 per thousand (guaiac) and 3.4 per thousand (immunological). In most cases, cervical cancer screening was undertaken opportunistically, with an estimated coverage of 69.0%. CONCLUSIONS: In Spain, cancer screening is being conducted in accordance with national and international recommendations. The fact that screening programmes are operated as a network has led to a high degree of consensus as to the methodology and information systems to be used to enable joint evaluation.

La importancia del diagnóstico precoz como forma de control del cáncer de mama / The importance of early diagnosis as a control of breast cancer

El cáncer de mama es el tumor más frecuente en las mujeres,diagnosticándose más de un millón de casos cada año. Laforma más eficaz de controlar una enfermedad es evitar suaparición reduciendo la exposición a los factores causales dela misma. Sin embargo, el conocimiento actual sobre la epidemiologíadel cáncer de mama es limitado. A pesar de la multitudde estudios realizados, tomados en conjunto, los factoresde riesgo clásicos explican menos del 50% de los casos observados,por lo que por ahora se descarta la posibilidad de evitarsu aparición. Por el contrario, su detección precoz, con la posterioraplicación de tratamientos más efectivos, se ha demostradocomo un método válido para disminuir su mortalidad.Existe un consenso general en la recomendación de aplicarcon carácter poblacional programas de cribado cáncer demama a todas las mujeres de 50 a 69 años utilizando la mamografíacomo único test. En 1990 se implantó en España elprimer programa poblacional y progresivamente se fueron desarrollandootros hasta completar en la actualidad el 100% decobertura nacional.La estrategia en cáncer del Sistema Nacional de Salud recogela existencia de programas de cribado de cáncer de mamapara todas las mujeres de 50 a 69 años. También se fija la necesidadde garantizar el acceso a programas de seguimientoorganizado de individuos con riesgo elevado y el acceso a unidadesespecializadas a personas con riesgo hereditario

Breast cancer is the most frequent tumour among women,with over a million cases diagnosed every year. The most efficientway of controlling a disease is to avoid its onset by reducingthe factors that cause it. However, the current understandingof the epidemiology of breast cancer is limited. In spite ofnumerous studies, classic risk factors taken as a whole explainless than 50% of observed cases. Therefore, the possibility ofavoiding the onset of this disease has been discarded for thetime being. However, its early detection and ensuing applicationof the most effective treatments has been shown to be avalid method to reduce mortality. There is a widespread consensusin recommending population-wide breast cancer screeningprogrammes for all women between 50 and 69, usingmammography as single test. The first population-wide screeningprogramme in Spain was implemented in 1990. Thiswas followed by others until today, when they cover 100% ofthe Spanish population.The cancer strategy of the National Health System includesbreast cancer screening programmes for all women between50 and 69. It also sets the need to guarantee access to organisedmonitoring programmes for high-risk individuals and accessto specialised units for patients with a hereditary risk

Comparison of early performance indicators for screening projects within the European Breast Cancer Network: 1989-2000.

In 1989 the European Breast Cancer Network (EBCN) was established by the first pilot projects for breast cancer screening, co-funded by the Europe Against Cancer programme. We report early performance indicators for these EBCN projects while taking into account their organizational setting. Out of 17 projects in the network, 10 projects from six European countries contributed aggregated data on number of invitations, screening examinations, and breast cancers detected over the period 1989-2000. Results were summarized separately for projects in centralized versus decentralized health care environments. The European Guidelines for quality assurance in mammography screening provided reference values for the performance indicators. The most prominent finding in this study was the higher participation rate in centralized versus decentralized projects (average participation in 1998: 74 versus 33%; P<0.001), whereas the invitation system and screening policy in these projects were similar. Detection rates and characteristics of cancers detected at initial and subsequent screening examinations showed no significant differences between centralized and decentralized projects. Even though early performance indicators for centralized versus decentralized projects were similar, the impact of breast screening on mortality from this disease at the population level will differ since the decentralized projects reach only part of the target population.

Programa de detección precoz de cáncer de mama. Resultados de proceso e indicadores de impacto (1990-2002) / Breast cancer screening program. Results of the process and impact indicators (1990-2002)

Fundamento. Existe un consenso general en la recomendación de aplicar con carácter poblacional programas de cribado de cáncer de mama. El Departamento de Salud puso en marcha en el año 1990 un Programa de Detección Precoz de Cáncer de Mama, con el objetivo de disminuir la mortalidad por este tumor, que en este momento está finalizando su séptima vuelta. El presente trabajo tiene como objetivo analizar los resultados obtenidos, describiendo los principales indicadores de proceso y predictores de impacto según los factores más determinantes. Material y métodos. Se han recopilado los datos de las exploraciones de cribado realizadas desde el comienzo del programa hasta el 31 de diciembre de 2002 clasificando por edad en el momento de la exploración, tipo de exploración y vuelta. Resultados. Durante el período se han realizado 354.575 exploraciones. Indicadores de proceso: en el 11,22 por ciento se recomendó realizar una exploración adicional. El 0,67 por ciento de las mujeres han sido enviadas a unidades hospitalarias para valoración diagnóstica. Se ha confirmado un tumor maligno en el 0,34 por ciento de las mujeres exploradas. A 8,37 por ciento de las mujeres se les ha recomendado realizar una exploración intermedia antes de la nueva de cribado. Indicadores predictores de impacto: la captación global es de 88,68 por ciento, la participación global de 87,91 por ciento y la adherencia al programa de 96,32 por ciento. La tasa de detección alcanza la cifra de 3,95 por 1.000 mujeres exploradas. De los tumores detectados, 19,17 por ciento son intraductales, y 37,23 por ciento de los invasivos tienen un tamaño igual o inferior a 10 mm. El 74,89 por ciento del total de tumores no presenta invasión ganglionar. Conclusiones. Considerando las referencias que para programas de cribado establece la Unión Europea, todos los indicadores predictores calculados superan los estándares exigidos (AU)

[Breast cancer screening program. Results of the process and impact indicators (1990-2002)]. / Programa de detección precoz de cáncer de mama. Resultados de proceso e indicadores de impacto (1990-2002).

BACKGROUND: There is a general consensus on the recommendation of applying breast cancer screening programs to the population. In March 1990, the Health Department set in motion a Program for the Early Detection of Breast Cancer, with the aim of reducing mortality due to this tumour. At present, the program is reaching the end of its seventh round. The present study aims to analyze the results obtained, describing the principal indicators of the process and the impact predictions according to the most determinant factors. METHODS: Data was collected for the screening explorations carried out from the start of the program up until December 31st 2002; the data was classified according to age at the time of exploration, type of exploration and round. RESULTS: During the period, 354,575 explorations were carried out. Process indicators: an additional exploration was recommended for 11.22% of the women. Naught point sixty seven percent (0.67%) of the women were sent to hospital units for a diagnostic evaluation. A malignant tumour was confirmed in 0.34% of the women subjected to exploration. It was recommended that 8.37% of the women should carry out an intermediate exploration before the next call from the screening program. Predictive impact indicators: global recruitment was 88.68%; global participation 87.91%; and adherence to the program was 96.32%. The rate of detection reached the figure of 3.95 per 1,000 women explored. Of the tumours detected: 19.17% were intraductal and 37.23% of the invasive tumours had a size equal to or below 10mm. Seventy-four point eighty nine percent (74.89%) of total tumours did not show ganglionary invasion. CONCLUSIONS: Considering the references established by the European Union for screening programs, all of the calculated predictive indicators exceed the required standards.

Breast cancer screening in Navarra: interpretation of a high detection rate at the first screening round and a low rate at the second round.

Our objective was to evaluate the on-going European pilot project for breast cancer screening in Navarra, Spain, and to predict the effects and costs of the programme in the long run. Observed results in Navarra, consisting of more than 100,000 screens, were compared with expected results. A microsimulation screening analysis model was used that included demographical, epidemiological and screening characteristics of Navarra. Alternative assumptions on epidemiological and screening characteristics were also addressed. The observed detection rate (5.9 per 1,000 screened women) in the first round was 18% higher than expected; the observed rate in the subsequent round (2.9) was 17% lower than expected. Longer pre-clinical durations, lower sensitivity or the existence of a high-risk group in Navarra could not satisfactorily explain the first and second round results together. Nevertheless, the programme will have an important health benefit for the women involved, due to an important trend in incidence in recent years and the relatively unfavourable clinical stage distribution in Navarra. The proportion T2+ cancers that will be prevented after 10 years of screening amounts to 36%. The annual mortality reduction in steady state is expected to range between 17% (if the observed rates in the second round indicate real screening performance) to 23% (if the first round indicates real performance). Our results demonstrate that a high detection rate in the first round is insufficient to evaluate the quality of a programme. Interval cancer rates, results of the subsequent round and size distributions are also crucial indicators of the quality of the screening programme and should be analysed in their specific context.

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.

Socioeconomic differences in cervical cancer: two case-control studies in Colombia and Spain.

OBJECTIVES: This study examined the causes of socioeconomic differences in invasive cervical cancer in two countries that differ substantially in cervical cancer incidence and economic development. METHODS: Data were derived from two case-control studies carried out in Spain and Colombia; there were 373 case subjects, 387 control subjects, and 425 husbands interviewed with a structured questionnaire. Exfoliated cells were obtained from cervical or penile scrapes and tested for human papillomavirus (HPV) DNA. RESULTS: Relative to better educated women, women with low educational levels in both countries reported fewer Pap smears and had a higher prevalence of HPV DNA. The prevalence ratio of HPV DNA across educational strata was twofold in Spain and fourfold in Colombia. In both countries, husbands of poorly educated women reported higher use of prostitutes than husbands of better educated women. In Colombia, 30% of husbands of poorly educated women harbored HPV DNA, compared with 10% of husbands of better educated women. CONCLUSIONS: Socioeconomic differences in invasive cervical cancer could be partly explained by differences in the prevalence of HPV DNA and by a lower use of preventive care.

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.

Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain.

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.

Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in southwestern Europe.

The main causes of cancer of the larynx and hypopharynx are smoking cigarettes and drinking alcohol. However, for these as well as for other cancers of the upper aerodigestive tract, some dietary components, mainly low consumption of fruit and vegetables, have been observed to be associated with increased cancer risk. We report results from a multicenter case-control study carried out in six regions of Europe located in northern Spain, northern Italy, Switzerland, and France. A total of 1,147 males with cancer (cases) and 3,057 population controls were interviewed on usual diet, lifelong drinking and smoking habits, and occupational history. Cancer cases had histologically verified epidermoid carcinomas. The cancers were classified in two anatomic sub-entities: the epilarynx (hypopharynx and upper part of the larynx), which enters into contact with the bolus and the air; and the endolarynx, through which air and tobacco smoke pass, but not the bolus. A previous report from this study found that alcohol drinking presents a greater risk factor for cancer of the epilarynx than for cancer of the endolarynx. The main results regarding diet indicate that high intake of fruit, vegetables, vegetable oil, fish, and low intake of butter and preserved meats were associated with reduced risk of both epilaryngeal and endolaryngeal cancers, after adjustment for alcohol, tobacco, socioeconomic status, and non-alcohol energy intake. Among nutrients, a reduced risk was found for high intake of vitamins C and E and for a high polyunsaturated/saturated fatty acids (P/S) ratio. While these variables are relevant in scoring nutritional behaviour, it remains unresolved whether the biologic properties of these nutrients play a role in the apparent protective effect.

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.

Sexually transmitted agents and cervical neoplasia in Colombia and Spain.

Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

[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)