Claudia Robles

HPV-FASTER: broadening the scope for prevention of HPV-related cancer

Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45–50-year age groups in some settings), paired with at least one HPV-screening test at age 30 years or older. Expanding the indications for HPV vaccination and much greater use of HPV testing in screening programmes has the potential to accelerate the decline in cervical cancer incidence. Such a combined protocol would represent an attractive approach for many health-care systems, in particular, countries in Central and Eastern Europe, Latin America, Asia, and some more-developed parts of Africa. The role of vaccination in women aged >30 years and the optimal number of HPV-screening tests required in vaccinated women remain important research issues. Cost-effectiveness models will help determine the optimal combination of HPV vaccination and screening in public health programmes, and to estimate the effects of such approaches in different populations.

Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: The Spanish bladder cancer study

An infectious etiology for bladder cancer has long been suspected. Merkel cell virus (MCV), BKV and JCV polyomaviruses are possible causative agents but data remain scarce. Therefore, we evaluated the seroresponse to these three polyomaviruses in association with bladder cancer risk. 1,135 incident bladder cancer subjects from five Spanish regions and 982 hospital controls matched by sex, age and region were included. 99% of cases were urothelial‐cell carcinomas. Antibody response against MCV, BKV and JCV was measured by enzyme immunoassay using Virus‐Like‐Particles. Our results show a similar seroprevalence in cases and controls: 64/60% for BKV, 83/82% for MCV and 87/83% for JCV. However, among seropositive subjects, higher median seroreactivities were observed in cases compared to controls for BKV (0.84 vs. 0.70, p‐value = 0.009) and MCV (1.81 vs. 0.65, p‐value < 0.001). Increased bladder cancer risk was observed for BKV (OR = 1.4, 95%CI 1.04–1.8) and for MCV (OR = 1.5, 95%CI 1.2–1.9), when comparing highest to lowest seroreactivity tertiles. The associations of BKV and MCV with bladder cancer were independent of each other and neither smoking status nor disease stage and grade modified them. Furthermore, no association was observed between seroresponse to JCV and bladder cancer. Therefore, we conclude that BKV and MCV polyomavirus infection could be related to an increased bladder cancer risk.

Antibody Response to Merkel Cell Polyomavirus Associated with Incident Lymphoma in the Epilymph Case–Control Study in Spain

Background: Merkel cell polyomavirus (MCV) has been identified as the cause of Merkel cell carcinoma. The increased incidence of chronic lymphocytic leukemia in Merkel cell cancer cohorts and the lymphotropic properties of the virus suggest a possible viral association with lymphomagenesis. To investigate this potential role, we explored seroreactivity against MCV VP1 capsids within the Epilymph case–control study in Spain. Methods: Serum samples from 468 incident lymphomas, categorized into up to 11 entities, and 522 controls frequency matched by age, sex, and recruitment center were tested for MCV antibodies by enzyme immunoassay using Virus-Like-Particles. Adjusted multinomial logistic regression was used to estimate the OR and 95% confidence interval (CI) associated to MCV seroprevalence. Immunosuppressed subjects were excluded. Results: MCV seroprevalence was 82% in controls and 85% in lymphoma cases. Among 11 lymphoma categories, MCV seropositivity was significantly higher in diffuse large B-cell lymphomas (DLBCL; 96.4%; OR = 6.1, 95%CI = 1.9–19.8), as compared with controls. MCV prevalences were also higher in follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and mature T-cell lymphoma but differences did not reach statistical significance. Lower prevalences were observed for multiple myeloma and other B-cell lymphoma. Exclusion of samples collected after start of treatment did not change the results. In a subset analysis, no significant association was observed between BKV and JCV seroprevalence and DLBCL. Conclusion: The association observed between serologic evidence of MCV exposure and DLBCL warrants further research. Impact: MCV might be involved in the pathway of DLBCL and other lymphomas. Cancer Epidemiol Biomarkers Prev; 21(9); 1592–8. ©2012 AACR.

Hormonal contraception and postmenopausal hormone therapy in Spain: time trends and patterns of use.

Objective:This study aims to describe time trends in and patterns of use of hormonal contraception and postmenopausal hormone therapy and to identify factors associated with their use among Spanish women. Methods:We performed a cross-sectional analysis using data from 1,954 population controls (aged 24-85 y) in 12 provinces of Spain who were enrolled in the Multi Case-Control Spain study (2007-2013). Data were collected from a questionnaire conducted face-to-face by trained personnel. We collected information on sociodemographic factors, lifestyle, sleep patterns, reproductive history, and occupational history. Results:Overall, 48.5% of Spanish women reported ever use of hormonal contraception, and 9.8% of women in the postmenopausal group reported use of postmenopausal hormone therapy. Younger cohorts used hormonal contraception for a longer period, whereas postmenopausal hormone therapy use dramatically dropped in the 2000s. Women with higher education levels (including education of partners) and smoking history were the most probable users of hormonal contraception, whereas inverse associations were observed among housewives, obese women, and nulliparous women. Postmenopausal hormone therapy use was associated with a surgical or therapeutic cause of menopause and with occupational history of rotating shifts. Conclusions:In this Spanish population, several demographic, lifestyle, occupational, and reproductive factors are associated with use of hormonal compounds. Characterizing hormonal users and monitoring trends in the use of these hormonal compounds are essential from a public health perspective.

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study

Background:Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma.Methods:We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study.Results:Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women.Conclusions:Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

Impact of operational factors on HPV positivity rates in an HPV‐based screening study in Colombia

To assess the effect of operational factors on the positivity rates of three HPV assays.

Adherence to the Western, Prudent, and Mediterranean dietary patterns and chronic lymphocytic leukemia in the MCC-Spain study.

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings.

Established and suggested exposures on CLL/SLL etiology: Results from the CLL-MCC-Spain study

INTRODUCTION Chronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLL METHODS: Using the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions. RESULTS Among the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend<0.016) and for type II diabetes. CONCLUSION We confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted.

P222 Pesticide exposure and chronic lymphocytic leukaemia using the spanish job-exposure matrix (matemesp)

This abstract was published in error and withdrawn at the author’s request.

Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study

BackgroundEpstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia.MethodsInformation on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models.ResultsAlmost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers.ConclusionsHighly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia.