Nieves Ascunce

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.

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.

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.

A pooled analysis of interval cancer rates in six European countries.

The objective of this study was to assess detection rates and interval breast cancer (IC) rates from eight programmes in the European Breast Cancer Screening Network. A common data collection protocol was used to explore differences in IC rates among programmes and discuss their potential determinants. Pooled analysis was used to describe IC rates by age, compliance in screening, recall rate, screening detection (SD) rate and expected breast cancer incidence. Participation in screening averaged 77.9% (range 42.6–88.7%), recall rate 5.4% (range 3.3–17.7%) in the initial and 3.4% (range 1.8–8.9%) in the subsequent screening rounds, and SD rate was 60.4 (range 41.6–91) per 10 000 women in initial and 38.5 (range 31.3–62.6) in subsequent screens. IC rate during first 12 months after screening was 5.9 (range 2.1–7.3) per 10 000 women screened negative and 12.6 (range 6.3–15) in the second year of the interval. IC comprised 28% of the IC and SD cancers. The ratio between IC rate and expected incidence was 0.29 for the first 12 months and 0.63 for the 13–24 months period. Sensitivity was higher for the ages 60–69 years and for initial tests than subsequent tests. There were distinct differences in the IC rates between programmes. The results of this study reveal large variations in screening sensitivity and performance. Pooled evaluation of some process indicators within the European breast cancer screening programmes proved to be feasible and is likely to be useful for the future, particularly if it is performed regularly and extensively.

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.

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 womens characteristics affect the cumulative false-positive risk. METHODS This is a retrospective cohort study of 1565364 women aged 45-69 years who underwent 4739498 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.Background: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and womens 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.

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.

Decline in age at menarche among Spanish women born from 1925 to 1962

BackgroundWhile the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme.MethodsThe study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates.ResultsAmong women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth.ConclusionWe report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.

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 LI‐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.

Effect of start age of breast cancer screening mammography on the risk of false-positive results.

OBJECTIVE To estimate the false-positive (FP) risk according to the start age of mammography screening (45-46 or 50-51 years). METHOD Data from eight regions of the Spanish breast cancer screening programme from 1990 to 2006 were included (1,565,364 women). Discrete time-hazard models were used to ascertain the effect of age and time-related, programme-related and personal variables on FP leading to any further procedure and to invasive procedures (FPI). In a subset we estimated the differential FP risk of starting screening at 45-46 years (175,656 women) or 50-51 (251,275). RESULTS A start age of 45-46 versus 50-51 years increased both FP (OR=1.20; 95%CI: 1.13-1.26) and FPI risks (OR=1.43 (95%CI: 1.18-1.73).Other factors increasing FP risk were premenopausal status (FP OR=1.26; 95%CI: 1.23-1.29 and FPI OR=1.22; 95%CI: 1.13-1.31), prior invasive procedures (FP OR=1.52; 95%CI: 1.47-1.57 and FPI (OR=2.08; 95%CI: 1.89-2.28) and family history (FP OR=1.16; 95%CI: 1.12-1.20 and FPI OR=1.26; 95%CI: 1.13-1.41). FP risk was increased by double reading (OR=1.36; 95%CI: 1.23-1.51) and FPI risk by double views (OR=1.34; 95%CI: 1.18-1.52). Both the cumulative FP and FPI risks were higher in women commencing screening at 45-46 years versus 50-51 years (33.30% versus 20.39% and 2.68% versus 1.76%). CONCLUSIONS Starting screening earlier increases the cumulative risk of FP and FPI.