HPV self-sampling among cervical cancer screening users in Spain: A randomized clinical trial of on-site training to increase the acceptability.

A randomized clinical trial was conducted to compare the impact of two different instructions on vaginal self-sampling in its acceptability and willingness for future screening rounds among women attending cervical cancer screening (CCS). From November 2018 to May 2021, women aged 30-65 living in Spain attending CCS were randomized 1:1 in two arms. In the "On-site training arm (TRA)", women took a self-sample at the primary health care centre following provider's instructions. In the "No on-site training arm (NO-TRA)" women only received instructions to take self-sample at home. All women had to return a new sample collected at home one month after the baseline visit and an acceptability questionnaire. The proportion of self-samples returned, and acceptability was computed by the study arm. A total of 1158 women underwent randomization, 579 women per arm. At follow-up, women in TRA were more likely to return the home sample than women in the NO-TRA (82.4% and 75.5% respectively; p = 0.005). Over 87% of all participants favoured home-based self-sampling approach for future CCS, similar by arm. Over 80% of women in both arms chose to collect and return the self-sample at a health centre or pharmacy. Home-based self-sampling was a highly accepted strategy for CCS in Spain. Trying it first with prior on-site training at the health centre significantly increased the sample's return suggesting that a provider's supervision raised confidence and adherence. It is an option to consider when moving to self-sampling in established CCS. Preferred delivery sites most likely contextual. Registration on ClinicalTrials.gov: NCT05314907.

Cervical cancer screening programs in Latin America: current recommendations for facing elimination challenges.

OBJECTIVE: To describe current cervical cancer screening program guidelines in Latin America. MATERIALS AND METHODS: We searched official recommendations for the general population and women living with HIV (WLHIV) by reviewing official sources from 19 countries; these data were supplemented with a consultation carried out by the WHO with the Ministries of Health. RESULTS: Screening policies vary significantly in regard to target populations, primary tests, and screening intervals. Sixteen countries have recently updated their recommendations; however, cytology remains the primary screening test for most countries. Eleven countries have introduced HPV tests, and eight countries have implemented screen-and-treat algorithms; only three countries have developed evidence-based guidelines. All countries but Costa Rica have specific recommendations for WLHIV. CONCLUSIONS: Although most countries have updated their screening policies, only a few are properly alig-ned with the WHO elimination strategy. Recommendations for WLHIV require better integration with cervical cancer screening programs.

Impact of a single-age cohort human papillomavirus vaccination strategy in Catalonia, Spain: Population-based analysis of anogenital warts in men and women.

Extensive multiple-age cohort human papillomavirus (HPV) vaccination has proved to be highly effective. We aimed to determine the 8-year population impact of a female single-age cohort HPV vaccination programme on the incidence of anogenital warts (AGW). In 2008, Catalonia initiated a school-based quadrivalent HPV vaccination programme targeting 11-year-old girls, achieving coverage over 80%. Data on diagnoses of AGW and genital herpes were obtained from a population-based database of electronic health records covering 74% of the population. The annual incidence rates from 2009 to 2016 were calculated, stratified by age and sex using Joinpoint regression to estimate trends and annual percentage changes (APC). Among women aged 16-19 years, the AGW incidence decreased by 61% from 2012 to 2016 (APC -19.4%; 95% CI: -30.0 to -7.3). In contrast, the incidence of genital herpes in same-aged women increased throughout the study period (APC 11.1%; 95% CI: 7.2-15.2). Among men aged 20-22 years, the increasing incidence of AGW shifted to a downward trend in 2013 (APC 2009-2013: 17.0%; 95% CI: 8.2-26.5; and APC 2013-2016: -4.5%; 95% CI: -14.6 to 6.9). A similar pattern was observed among men aged 23-25 years (APC 2009-2014: 16.0%; 95% CI: 12.0-20.2; and APC 2014-2016: -6.0%; 95% CI: -18.4 to 8.3). In contrast to AGW, among men aged 20-25 years, the incidence of genital herpes increased over this period. Our study strongly suggests that a single-cohort HPV vaccination strategy with high vaccine uptake not only provides direct benefit in the vaccinated cohorts but also extends protection through a herd effect to unvaccinated men.

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.

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.

Cervical cancer screening coverage in the Americas region: a synthetic analysis.

Background: The Americas region has the lowest (North America) and the second highest (Latin America and Caribbean) cervical cancer (CC) mortality worldwide. The lack of reliable data on screening coverage in the region hinders proper monitoring of the World Health Organization (WHO) CC elimination initiative. Methods: For this synthetic analysis, we searched data on CC screening coverage from official sources and national health surveys, supplemented with a formal WHO country consultation. Context data were obtained from official sources (income, health expenditure, inequality-adjusted human development index -IHDI-, universal health coverage, CC incidence/mortality). Country age-specific coverages for 2019 by screening interval were computed. Missing data were imputed through a multi-step algorithm. Beta-regression and Poisson-regression models were used to analyse associations between context variables, screening coverage, and CC mortality. Findings: We included data from 37 countries in the Americas. Data on coverage of HPV testing was scarce, and for many countries only Pap-smear coverage data was available. Overall, 78%, 34%, 60%, and 67% of women aged 25-65 years have been screened ever in their lifetime, and in the previous year, 3 years, and 5 years, respectively. By sub-region, 3-year coverage ranges from 48% (South America) to 72% (North America). Twenty-four countries showed screening coverage below 70%. Income and health system type were associated with screening coverage, but coverage was not associated with CC mortality. Interpretation: In the Americas region 35.1% and 56.8% of countries report 3-year and 5-year coverage over 70%, respectively. Inequalities remain a major challenge for screening programs in the region. The elimination campaign should reinforce the transition to HPV testing and strengthen surveillance systems. Funding: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020.

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Impact of the COVID-19 pandemic on cervical cancer screening participation, abnormal cytology prevalence and screening interval in Catalonia.

Background: The COVID-19 pandemic led to a national lockdown and the interruption of all cancer preventive services, including cervical cancer screening. We aimed to assess the COVID-19 pandemic impact on opportunistic screening participation, abnormal cytology (ASCUS+) prevalence and screening interval in 2020 and 2021 within the Public Health System of Catalonia, Spain. Methods: Individual data on cytology and HPV testing of women aged 25-65 from 2014 to 2021 were retrieved from the Information System for Primary Care Services (SISAP). Time-series regression models were used to estimate expected screening participation and abnormal cytology prevalence in 2020 and 2021. The impact was determined by comparing observed and expected values (ratios). Additionally, changes in screening interval trends between 2014 and 2021 were assessed by fitting a Piecewise linear regression model. Results: Cervical cancer screening participation decreased by 38.8% and 2.2% in 2020 and 2021, respectively, with the most significant impact on participation (-96.1%) occurring in April 2020. Among older women, participation was lower, and it took longer to recover. Abnormal cytology prevalence was 1.4 times higher than expected in 2020 and 2021, with variations by age (range=1.1-1.5). From June 2020 onwards, the screening interval trend significantly changed from an increase of 0.59 to 3.57 months per year, resulting in a median time of 48 months by December 2021. Conclusions: During the pandemic, fewer women have participated in cervical cancer screening, abnormal cytology prevalence has increased, and the screening interval is more prolonged than before. The potential cervical cancer lifetime risk implications highlight the need for organized HPV-based screening.

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.

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

BACKGROUND: Human 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. METHODS: The 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. RESULTS: A 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). CONCLUSION: This 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.

Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis.

BACKGROUND: Cervical cancer screening coverage is a key monitoring indicator of the WHO cervical cancer elimination plan. We present global, regional, and national cervical screening coverage estimates against the backdrop of the 70% coverage target set by WHO. METHODS: In this review and synthetic analysis, we searched scientific literature, government websites, and official documentation to identify official national recommendations and coverage data for cervical cancer screening for the 194 WHO member states and eight associated countries and territories published from database inception until Oct 30, 2020, supplemented with a formal WHO country consultation from Nov 27, 2020, to Feb 12, 2021. We extracted data on the year of introduction of recommendations, the existence of individual invitation to participate, financing of screening tests, primary screening and triage tests used, recommended ages and screening intervals, use of self-sampling, and use of screen-and-treat approaches. We also collected coverage data, either administrative or survey-based, as disaggregated as possible by age and for any available screening interval. According to data completeness and representativeness, different statistical models were developed to produce national age-specific coverages by screening interval, which were transformed into single-age datapoints. Missing data were imputed. Estimates were applied to the 2019 population and aggregated by region and income level. FINDINGS: We identified recommendations for cervical screening in 139 (69%) of 202 countries and territories. Cytology was the primary screening test in 109 (78%) of 139 countries. 48 (35%) of 139 countries recommended primary HPV-based screening. Visual inspection with acetic acid was the most recommended test in resource-limited settings. Estimated worldwide coverage in women aged 30-49 years in 2019 was 15% in the previous year, 28% in the previous 3 years, and 32% in the previous 5 years, and 36% ever in lifetime. An estimated 1·6 billion (67%) of 2·3 billion women aged 20-70 years, including 662 million (64%) of 1·0 billion women aged 30-49 years, had never been screened for cervical cancer. 133 million (84%) of 158 million women aged 30-49 years living in high-income countries had been screened ever in lifetime, compared with 194 million (48%) of 404 million women in upper-middle-income countries, 34 million (9%) of 397 million women in lower-middle-income countries, and 8 million (11%) of 74 million in low-income countries. INTERPRETATION: Two in three women aged 30-49 years have never been screened for cervical cancer. Roll-out of screening is very low in low-income and middle-income countries, where the burden of disease is highest. The priority of the WHO elimination campaign should be to increase both screening coverage and treatment of detected lesions; however, expanding the efforts of surveillance systems in both coverage and quality control are major challenges to achieving the WHO elimination target. FUNDING: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020. TRANSLATIONS: For the French, Spanish translations of the abstract see Supplementary Materials section.

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.

Long-term protection of HPV test in women at risk of cervical cancer.

OBJECTIVE: To evaluate the 9-year incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cumulative adherence to perform a next test in a cohort of women aged 40+ years with no cervical screening cytology within a window of 5 years (underscreened women), after baseline cervical cytology and HPV tests. METHODS: In Catalonia, Spain, co-testing with cytology and HPV test has been recommended in the Public Health system since 2006 for underscreened women. In 2007, 1,594 women with underscreened criteria were identified and followed through medical records form Pathological Department. 9-year cumulative incidence of histologically confirmed CIN2+ and cumulative adherence to perform a next test were estimated using Kaplan-Meier statistics. RESULTS: Follow-up was available for 1,009 women (63.3%) resulting in 23 women with. CIN2+ (2.3%). Of them, 4 women (17%) had both tests negative at baseline (3CIN2 and 1CIN3) with cumulative incidence of CIN2+ of 0.4% (95% CI: 0.1-1.4) at 5-years and 1.3% (95% CI: 0.4-3.7) at 9-years. During the first year, the prevalence among women with both tests positive was 27.0% (95% CI: 13.0-50.6) for CIN2+. Lost to follow-up was higher among women with both tests negative compared to those with both positive tests (38.7% vs 4.2%, p-value <0.001). 40.5% of the women HPV-/cyto- had a re-screening test during the 4 years following the baseline, increasing until 53.5% during the 6 years of follow-up. CONCLUSIONS: HPV detection shows a high longitudinal predictive value at 9-year to identify women at risk to develop CIN2+. The data validate a safe extension of the 3-year screening intervals (current screening interval) to 5-year intervals in underscreened women that had negative HPV result at baseline. It is necessary to establish mechanisms to ensure screening participation and adequate follow-up for these women.

Prevalence and genotype distribution of cervical human papilomavirus infection in the pre-vaccination era: a population-based study in the Canary Islands.

OBJECTIVE: National Spanish studies show that prevalence of cervical human papillomavirus (HPV) infection in the female population is increasingly frequent, with an overall estimate of 14% in women aged 18-65 years. The objective of this study is to know the prevalence and distribution of HPV types in the female population of the Canary Islands prior to the introduction of HPV vaccines and to investigate the associated clinical and sociodemographic factors. METHODS: Based on the Primary Health Care database, a sample of adult women (aged 18-65 years) of Gran Canaria (GC) and Tenerife (TF) stratified into nine age groups was carried out between 2002 and 2007. Women were contacted by postal letter and telephone call and were visited in their primary care centre. A clinical-epidemiological survey was completed and cervical samples were taken for cytological study and HPV detection. HPV prevalence and its 95% CI were estimated, and multivariate analyses were performed using logistic regression to identify factors associated with the infection. RESULTS: 6010 women participated in the study, 3847 from GC and 2163 from TF. The overall prevalence of HPV infection was 13.6% (CI 12.8%-14.5%) and 11.1% (CI 10.3%-11.9%) for high-risk types. The most frequent HPV type was 16 followed by types 51, 53, 31, 42 and 59. HPV types included in the nonavalent vaccine were detected in 54.1% of infected women. Factors associated with an increased risk of infection were: young ages (18-29 years), the number of sexual partners throughout life, not being married, being a smoker, and having had previous cervical lesions or genital warts. CONCLUSIONS: It is confirmed that prevalence of HPV infection in the female population of the Canary Islands is high, but similar to that of Spain, HPV 16 being the most frequent genotype. The determinants of infection are consistent with those of other populations.

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.

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 chi2 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.

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.

Screening of cervical cancer in Catalonia 2006-2012.

The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008-2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden.

[Coverage of cervical cancer screening in Catalonia, Spain (2008-2011)]. / Cobertura del cribado de cáncer de cuello uterino en Cataluña (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.

Burden of human papillomavirus infection and related diseases in Israel.

This manuscript provides the available data on the burden of human papillomavirus (HPV) infections and HPV-related diseases in Israel. The incidence of cervical intraepithelial neoplasia grade 3 (CIN3) among Jewish women was 17.4 per 100,000 in 2007, showing an increase since 1997. The incidence of cervical cancer was 5.3 per 100,000 Israeli Jewish women and 2.3 per 100,000 Israeli non-Jewish women in 2007. This rate is relatively low compared to other developed countries, and could be explained by cultural and religious factors such as male circumcision or sexual behavior. Mortality rates were around 1.5 per 100,000 Israeli women in 2007. Incidences of other anogenital, oral cavity, and pharynx cancers are very low, below 1.0 per 100.000 Israeli women and men. Information is scarce on HPV prevalence and HPV type distribution among women with cervical cancer. HPV types 16 and 18 were the two most common types in both preneoplastic lesions and cervical cancer, representing 60% of total invasive cases. Data on genital warts show an incidence rate of 239 per 100,000 men and 185 per 100,000 women, similar to that found in other Western countries. Despite these low incidences, it is important to improve the information on the overall burden of HPV-related morbidity and on the HPV prevalence to evaluate an organized cervical cancer screening program and the introduction of the HPV vaccine in the national school-based vaccine program. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.