Esther Roura

Coverage and Factors Associated With Cervical Cancer Screening: Results From the AFRODITA Study: A Population-Based Survey in Spain

Objective. To quantify the coverage and monitor the factors associated with opportunistic cervical cytological screening in Spain. Materials and Methods. Population-based survey of selected women through the Access Panel technique representative of the general population. A total of 6,852 women (60%) replied to the questionnaire; 981 (14.3%) were excluded from the analysis because they did not meet the screening criteria. Data were adjusted for regions, age group, socioeconomic level (SEL), and municipality size. Moreover, information was collected on preventive gynecological revisions received. Categorical variables were evaluated through the &khgr;2 test of heterogeneity or through a liner test for trend. Multivariate prevalence odds ratios were used to identify statistically significant determinants of screening using logistic regression modeling. Results. The percentage of women 18 to 65 years old with a Pap smear within the last 3 years was 75.6%. Insufficient coverage was observed in women older than 55 years (66%), who live in rural areas (66%), with lower SEL (65%), and in some regions (61%-66%). The factors positively associated with screening were age 26 to 55 years, certain regions, higher SEL, larger municipality size, ever being pregnant, early age at first sexual intercourse, knowledge about cervical cancer and human papillomavirus, and, very strongly, ever use of contraceptive methods. An overuse of cytology can be assumed, as a result of opportunistic screening. Conclusions. In Spain, the coverage of cytological screening reached 75% of the population, but with inefficiencies in some aspects. To rationalize its use, the Spanish consensus screening protocol must be followed.

Prevalence and genotype distribution of human papillomavirus infection of the cervix in Spain: The CLEOPATRE study

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer. The aim of this study was to estimate the prevalence of cervical HPV infection and HPV type‐specific distribution among women attending cervical cancer screening in Spain during 2007 and 2008. Women aged 18–65 years were recruited according to an age‐stratified sampling method. Liquid‐based cervical samples were collected and analyzed for cytology, HPV detection, and genotyping. HPV genotyping was determined using the INNO‐LiPA HPV Genotyping Extra Reverse Hybridization Line Probe Assay. Prevalence estimates were age‐standardized using 2001 Spanish census data. The present study included 3,261 women. Age‐standardized HC2‐based HPV prevalence was 14.3% (95% CI, 13.1–15.5) among women aged 18–65 years, and 28.8% (26.6–31.1) among women aged 18–25 years. High‐risk HPV types were detected in 12.2% (95% CI, 11.1–13.4) of HPV‐tested women, representing 84.0% of HPV‐positive samples. Multiple infections were present in 4.1% (95% CI, 3.4–4.8) of HPV‐tested women (25.0% of HPV‐positive samples). The most common high‐risk HPV‐types among HPV‐tested women were 16 (2.9%), 52 (1.8%), 51 (1.6%), 31 (1.3%), and 66 (1.2%). HPV‐type 16 was present in 16.9% of HPV‐positive samples. One or more of the HPV vaccine types 6/11/16/18 were detected in 3.8% of HPV‐tested women (22.1% of HPV‐positive samples). Though not a true population‐based survey, this study provides valuable baseline data for future assessment of the impact of current HPV vaccination programs in Spain. The high prevalence of HPV infection among young women may reflect recent changes in sexual behavior. J. Med. Virol. 84:947–956, 2012.

Smoking as a major risk factor for cervical cancer and pre-cancer: Results from the EPIC cohort

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow‐up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case–control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV‐2). Cervical samples were not available for HPV‐DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case–control studies. In the cohort analyses smoking status, duration and intensity showed a two‐fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two‐fold reduced risk. In the nested case–control study, consistent associations were observed after adjustment for HPV, CT and HHV‐2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.

Age at sexual initiation and number of sexual partners in the female Spanish population Results from the AFRODITA survey.

OBJECTIVES The AFRODITA study was designed to describe patterns relating to the number of lifetime sexual partners (SP) and age at first sexual intercourse (AFSI) by geographic region in a representative sample of Spanish women. STUDY DESIGN A representative sample of the female Spanish population was obtained using the Access Panel Technique. Postal questionnaires were sent to 11,086 women aged 18-70 years. Data were collected on AFSI, number of sexual partners, contraceptive methods, cervical cancer screening and socio-demographic characteristics. RESULTS The average AFSI was 20.9 years. AFSI below the age of 19 years was reported by 30.8% of the women. Among sexually active women, 70.6% reported being monogamous and 6.4% reported > or = 5 lifetime sexual partners. Younger age at interview was strongly related to earlier AFSI and to higher number of lifetime sexual partners. Women younger than 25 were 39 times more likely to have an AFSI before age 18 than women over age 55. The percentage of women aged less than 25 reporting two or more sexual partners was four times higher than that of women 56 and older. In the multivariate analysis, having two or more sexual partners was independently associated with young age, early AFSI, having ever used oral contraceptives, living in an urban area, having had a screening Pap test in the last 3 years, having a sexually transmitted infection and nuliparity. CONCLUSIONS This study confirms important changes in the sexual behaviour of Spanish women. Younger cohorts show a younger age at sexual initiation and higher number of sexual partners. These are key factors that may induce changes in the human papillomavirus (HPV) prevalence and the cervical cancer incidence in Spain.

Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study.

Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow‐up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72–0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65–1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta‐carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre- Cancer: Results from the EPIC Cohort

Background In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4–0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.

Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study

BackgroundHuman papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain.MethodsThe CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection.ResultsA lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01).ConclusionThis is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection.

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed‐up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV‐2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2–2.0) and 1.8 (1.1–2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4–2.4) and 7.4 (2.8–19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9–1.9) and 2.3 (1.3–4.1) for CT seropositivity, and 1.4 (1.0–2.0) and 1.5 (0.9–2.6) for HHV‐2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR = 10.2 (3.3–31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non‐STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV‐2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development.

Coverage of Cervical Cancer Screening in Catalonia for the Period 2008–2011 among Immigrants and Spanish-Born Women

Background: Female immigration in Catalonia, Spain, increased dramatically in the last 10 years. The Public Health system in the Region, provides a free of charge opportunistic cervical cancer screening. Aim: This study examines cervical cancer screening coverage and prevalence of cytology abnormalities in Catalonia by immigration status. Methods: The study analyzes the cytologies registered among women aged 25–65 that have been attended at the Primary Health Centers (PHC) for any reason (n = 1,242,230) during 2008–2011. Coverage was estimated from Governmental data base Information System Primary Care (SISAP) that includes 77% of PHC. The database is anonymous, and includes information on age, country of birth, diagnostic center, and cytology results. Results: During the period 2008–2011, 642,643 smears were performed in a total of 506,189 women over 14 years, of whom 18.3% were immigrants. Cytology coverage was higher among immigrant women compared to Spanish born (51.2 and 39% respectively). Immigrant women also had a higher prevalence of abnormal Paps compared to the Spanish population, 4.5 and 2.9% respectively (p < 0.001). Conclusion: Immigrant women in Catalonia had a high access to the Public Health Services and to cervical cancer screening facilities. The higher prevalence of abnormal cytologies in immigrant women compared to native women indicates the relevance to prioritize cervical cancer screening activities on a regular base in new comers.

Coverage of cervical cancer screening in Catalonia, Spain (2008-2011)

OBJECTIVE To estimate cervical cytology coverage for the period 2008-2011 by age groups and health regions from data recorded in the medical records of women attending centers within the Catalan national health system. METHODS The data used to estimate coverage were obtained from the primary care information system. This information was anonymous and included age, center, date, and the results of cytological smears for a total of 2,292,564 women aged 15 years or more. RESULTS A total of 758,690 smears were performed in 595,868 women. Among women aged 25-65 years, the estimated coverage was 32.4% of the assigned population and was 40.8% in the population attended. Geographical variation was observed, with higher coverage among health regions closer to Barcelona. Abnormal Pap smears increased slightly from 2008 to 2011 (from 3% to 3.5%, respectively, p <0.001). In women with a negative first smear, the mean interval until the second smear was 2.4 years, but only 50% of women with a negative first smear in 2008 attended a second round during the study period. CONCLUSIONS Cervical screening coverage in the National Health Service of Catalonia includes one in three women. Second round participation was poor. Existing computer systems in primary care centers can ensure monitoring of population-based screening programs for cervical cancer. These systems could be used to plan an organized screening program to ensure wider coverage and better follow-up.