Performance of BD Onclarity HPV assay on FLOQSwabs vaginal self-samples.

This study assessed the accuracy of high-risk human papillomavirus testing of BD Onclarity HPV (Onclarity) assay on vaginal self-collected FLOQSwab versus cervical samples to ensure similar accuracy to detect cervical intraepithelial neoplasia. Testing was performed on two automated platforms, BD Viper LT and BD COR, to evaluate the effect of machine and using two vaginal self-samples to analyze the influence of collection, transport, and freezing-unfreezing on the results. A cervical sample and two self-samples were collected from 300 women. The first collected vaginal and the cervical sample were tested on BD Viper LT, and the second swab was frozen and subsequently tested on both automated systems. Test results on vaginal and cervical specimens were considered the index and comparator, respectively; colposcopy and histology were reference standards. Relative sensitivity for ≥CIN2 on vaginal samples analyzed versus the cervical sample was 1.01 (0.97-1.06), 1.01 (0.97-1.06), and 1.00 (0.95-1.05), for the first, second self-collected sample tested on BD VIPER LT, and second self-collected sample tested on BD COR, respectively. Relative specificity was 0.83 (0.73-0.94), 0.76 (0.67-0.87), and 0.82 (0.73-0.92) using the three different workflows. Cut-off optimization for human papillomavirus (HPV) positivity defined at Ct ≤38.3 for HPV16, ≤ 34.2 for HPV18, and ≤31.5 for all other types showed an increased relative specificity with similar sensitivity. No significant difference was observed between self-samples tested with the two platforms and between first- and second-collected swabs. Onclarity assay on FLOQSwab using both platforms showed similar sensitivity but lower specificity to detect ≥CIN2 compared to cervical samples. By cut-off optimization, non-inferior specificity could be reached. IMPORTANCE: Human papillomavirus (HPV) testing on self-collected vaginal samples has been shown to improve women's participation to cervical cancer screening programs, particularly in regions with limited access to health care. Nevertheless, the introduction of self-sampling in cervical cancer screening programs requires prior clinical validation of the HPV assay in combination with a self-sample collection device, including also the laboratory workflow and automation required for high-throughput testing in screening. In this study, the performance of BD Onclarity HPV on FLOQSwab-collected vaginal self-samples has been compared to clinician-taken liquid-based cytology samples, to detect high-grade cervical intraepithelial neoplasia using two high-throughput platforms, BD Viper LT and BD COR. The study findings have shown a similar performance of BD Onclarity on testing self-collected samples, confirming the validation of the proposed pre-analytical and analytical protocols for their use in cervical cancer screening programs based on self-collected vaginal samples.

Clinical Accuracy of Alinity m HR HPV Assay on Self- versus Clinician-Taken Samples Using the VALHUDES Protocol.

The VALHUDES protocol was established to evaluate clinical accuracy of human papillomavirus (HPV) assays to detect cervical precancer on first-void urine (FVU) and vaginal self-samples versus matched clinician-collected cervical samples (CCSs). Here we evaluated clinical performance of Alinity m HR HPV assay in a colposcopy referral population. Home-collected FVU (Colli-Pee FV 5020) 1 day before colposcopy (n = 492), at-clinic collected dry vaginal self-samples [multi-Collect Swab (mC; n = 493), followed by Evalyn Brush (EB; n = 233) or Qvintip (QT; n = 260)] and matched CCSs, were available for the study. Sensitivity to detect cervical intraepithelial neoplasia grade 2 or higher (CIN2+) of Alinity testing on FVU (ratio, 0.94; 95% CI, 0.85-1.03), mC (ratio, 1.00; 95% CI, 0.94-1.06), and EB/QT (ratio, 0.92; 95% CI, 0.85-1.00) was not different to CCSs. Specificity on FVU was similar to CCS (ratio, 1.02; 95% CI, 0.95-1.10), whereas specificity on mC was lower (ratio, 0.83; 95% CI, 0.76-0.90), but on EB/QT was higher (ratio, 1.08; 95% CI, 1.01-1.15) than on CCS. Accuracy on EB (sensitivity ratio, 0.96; 95% CI, 0.87-1.05; specificity ratio, 1.18; 95% CI, 1.06-1.31) was slightly better than on QT (sensitivity ratio, 0.88; 95% CI, 0.75-1.03; specificity ratio, 1.00; 95% CI, 0.92-1.09). In conclusion, clinical sensitivity of Alinity assay on all self-sample types was similar to cervical specimens. Adjustment of signal thresholds improved assay's accuracy to detect CIN2+ in all self-sample types.

Comparison of the Clinical Accuracy of Xpert HPV Assay on Vaginal Self-Samples and Cervical Clinician-Taken Samples within the VALHUDES Framework.

The accuracy of high-risk human papillomavirus testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALidation of HUman papillomavirus assays and collection DEvices for Self-samples and urine samples (VALHUDES) framework. Five-hundred and twenty-three women were recruited in five Belgian colposcopy clinics, of whom 483 (median age, 40 years; interquartile range, 31 to 49 years) were included in the main analysis (226 collected with Evalyn Brush and 257 collected with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard. The Xpert HPV assay had similar accuracy for cervical intraepithelial neoplasia ≥2 on self-collected versus clinician-collected samples [relative sensitivity, 0.96 (95% CI, 0.91-1.02); and relative specificity, 0.96 (95% CI, 0.89-1.04)]. The relative accuracy slightly differed by vaginal collection device [sensitivity ratios of 0.98 (95% CI, 0.90-1.06) and 0.94 (95% CI, 0.87-1.02) for Evalyn and Qvintip, respectively; specificity ratios of 1.06 (95% CI, 0.95-1.19) and 0.88 (95% CI, 0.80-0.98) for Evalyn and Qvintip, respectively]. No difference in cycle threshold values was observed between vaginal and cervical samples. In conclusion, the sensitivity of Xpert HPV assay for cervical intraepithelial neoplasia ≥2 on vaginal self-samples was similar to that of cervical specimens. The clinical specificity was lower than on clinician-collected samples when self-samples were taken with Qvintip.

HPV-based Cervical Cancer Screening on Self-samples in the Netherlands: Challenges to Reach Women and Test Performance Questions.

In 2017, cervical cancer screening in the Netherlands switched from cytology to human papillomavirus (HPV) testing using the validated PCR-based cobas 4800. Women could order and subsequently received a free self-sampling kit (Evalyn Brush) at their home address instead of clinician sampling. In the laboratory, the shipped brush was placed into 20 mL of PreservCyt fluid, before testing. In the first 2 years of the new program, only 7% of screening tests were performed on a self-sample. Those who chose self-sampling versus clinician sampling were more likely to have never been screened previously and differed also with respect to sociodemographic factors. Subsequent more active promotion and increasing the ease to obtain kits increased the proportion opting for self-sampling (16% in 2020). HPV positivity and detection rate of precancer (CIN3+) were lower in the self-sampling compared with the clinician-sampling group (adjusted ORs of 0.65 and 0.86, respectively). Although population differences may partially explain these results, self-samples may have been too dilute, thereby reducing the analytic and clinical sensitivity. The Dutch findings demonstrate the importance of optimizing outreach, specimen handling and testing protocols for self-samples to effectively screen the target population and reach in particular the women at highest risk for cervical cancer. See related article by Aitken et al., p. 183.

Clinical Performance of the RealTime High Risk HPV Assay on Self-Collected Vaginal Samples within the VALHUDES Framework.

The VALHUDES framework (NCT03064087) was established to evaluate the clinical accuracy of HPV testing on self-samples compared with HPV testing on matched clinician-taken cervical samples. Women referred to colposcopy due to previous cervical abnormalities were recruited at five Belgian colposcopy centers. A total of 486 pairs of matched cervical samples and vaginal self-samples were included in the analysis (228 collected with Evalyn Brush and 258 with Qvintip). The dry vaginal brushes were transferred into 20 mL ThinPrep PreservCyt solution. All specimens were tested with the Abbott RealTime High Risk HPV assay (Abbott RT). Testing on vaginal and cervical specimens was considered the index and comparator tests, respectively, and colposcopy and histology as the reference standard. The clinical sensitivity for CIN2+ of Abbott RT (cutoff ≤32 cycle number [CN]) on vaginal self-samples (Evalyn Brush and Qvintip combined) was 8% lower than on the cervical clinician-collected samples (ratio = 0.92 [95% CI, 0.87 to 0.98]), while the specificity was similar (ratio = 1.04 [95% CI, 0.97 to 1.12]). Sensitivity (ratio = 0.95 [95% CI, 0.89 to 1.02]) and specificity (ratio = 1.11 [95% CI, 0.995 to 1.23]) on Evalyn Brush samples was similar to cervical, while on Qvintip samples, the sensitivity was 12% lower than cervical samples (ratio = 0.88 [95% CI, 0.78 to 0.998]) with similar specificity (0.99 [95% CI, 0.90 to 1.10]). Exploratory cutoff optimization (cutoff ≤35 CN) resulted in an improvement of the relative sensitivity (self-sampling versus clinician sampling: ratio = 0.96 [95% CI, 0.91 to 1.02]) but yielded a loss in relative specificity (ratio = 0.92 [0.85 to 1.00]). The clinical accuracy of Abbott RT differed from the self-sampling device. However, after cutoff optimization, the sensitivity on self-samples taken with either of two vaginal brushes became similar to clinician-collected samples. IMPORTANCE Self-samples are becoming a crucial part of HPV-based cervical cancer screening programs to reach nonattendee women and increase screening coverage. Therefore, the VALHUDES framework was established to validate and evaluate HPV tests and devices on self-samples. Here, in the present manuscript, we evaluated the accuracy of the RealTime High Risk HPV assay (Abbott RT) on two different vaginal devices to detect cervical intraepithelial neoplasia grade two or higher (CIN2+). The study results demonstrated that the Abbott RT assay is similarly accurate on vaginal self-samples as on matched clinician-taken cervical samples after adjusting cutoff values. Moreover, we observed that some vaginal devices perform better than others in CIN2+ detection. We also underline the necessity of standardization and validation of general workflow and sample handling procedures for vaginal self-samples.

Analytical and clinical performance of extended HPV genotyping with BD Onclarity HPV Assay in home-collected first-void urine: A diagnostic test accuracy study.

BACKGROUND: Urine collection is a non-invasive self-sampling method offering the prospect of reaching women un(der)-screened for cervical cancer. The VALHUDES research framework was designed to address the lack of clinical accuracy data for high-risk (hr)HPV testing using urine samples. OBJECTIVES: Here, we report on the analytical and clinical accuracy of hrHPV testing on first-void urine, collected at home, using an extended HPV genotyping assay. STUDY DESIGN: Paired first-void urine (Colli-Pee with UCM, Novosanis; index test) and clinician-collected cervical samples (Cervex-Brush, Rovers in PreservCyt Solution, Hologic; comparator test) were collected from 492 women aged 19 to 72 years attending colposcopy (reference test, with histology if indicated) (VALHUDES; NCT03064087). Extended HPV genotyping was performed on paired samples with the BD Onclarity HPV Assay. Cut-offs defined for cervical samples were also applied for first-void urine. RESULTS: HrHPV testing in first-void urine was similarly sensitive for both CIN2+ (ratio 1.00; 95% CI: 0.93-1.07) and CIN3 (ratio 0.98; 95% CI: 0.88-1.08), and marginally less specific for

Validation of BD Onclarity HPV Assay on Vaginal Self-Samples versus Cervical Samples Using the VALHUDES Protocol.

BACKGROUND: In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples. METHODS: Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31-49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation. RESULTS: The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90-1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02-1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94-1.06) and 1.15 (95% CI, 1.05-1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79-1.04) and 1.03 (95% CI, 0.95-1.13), respectively for Qvintip. CONCLUSIONS: Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples. IMPACT: VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction.

BACKGROUND: Little is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. METHODS: Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender. RESULTS: Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8-100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5-99.8; and women, NPV = 98.7%, CI: 97.5-100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61-3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96-0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19-3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33-9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23-5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23-7.24), atrial fibrillation (OR = 2.90, CI: 1.26-6.70) and syncope-like events (OR = 7.56, CI: 2.26-25.30) were significant predictors of copeptin elevation. CONCLUSIONS: Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.

Characterization and Diversity of 243 Complete Human Papillomavirus Genomes in Cervical Swabs Using Next Generation Sequencing.

In recent years, next generation sequencing (NGS) technology has been widely used for the discovery of novel human papillomavirus (HPV) genotypes, variant characterization and genotyping. Here, we compared the analytical performance of NGS with a commercial PCR-based assay (Anyplex II HPV28) in cervical samples of 744 women. Overall, HPV positivity was 50.2% by the Anyplex and 45.5% by the NGS. With the NGS, we detected 25 genotypes covered by Anyplex and 41 additional genotypes. Agreement between the two methods for HPV positivity was 80.8% (kappa = 0.616) and 84.8% (kappa = 0.652) for 28 HPV genotypes and 14 high-risk genotypes, respectively. We recovered and characterized 243 complete HPV genomes from 153 samples spanning 40 different genotypes. According to phylogenetic analysis and pairwise distance, we identified novel lineages and sublineages of four high-risk and 16 low-risk genotypes. In total, 17 novel lineages and 14 novel sublineages were proposed, including novel lineages of HPV45, HPV52, HPV66 and a novel sublineage of HPV59. Our study provides important genomic insights on HPV types and lineages, where few complete genomes were publicly available.

Evolving social contact patterns during the COVID-19 crisis in Luxembourg.

We conducted an internet survey using Survey Monkey over six weeks to evaluate the impact of the government interventions on social contact patterns in Luxembourg. Participants were recruited via the science.lu website on March 25, April 2, April 16, May 1 during lockdown, and June 12 and June 25 after the lockdown to provide an estimate of their number of contacts within the previous 24 hours. During the lockdown, a total of 5,644 survey participants with a mean age of 44.2 years reported 18,118 contacts (mean = 3.2, IQR 1-4). The average number of contacts per day increased by 24% from 2.9 to 3.6 over the lockdown period. The average number of contacts decreased with age: 4.2 (IQR 2-5) for participants below 25 years and 1.7 (IQR 1-2) for participants above 64 years. Residents of Portuguese nationality reported a higher number of contacts (mean = 4.3, IQR 2-5) than Luxembourgish (mean = 3.5, IQR 2-4) or other foreign residents, respectively. After lockdown, 1,119 participants reported 7,974 contacts with 7.1 (IQR 3-9) contacts per day on average, of which 61.7% (4,917/7,974) occurred without a facemask (mean = 4.9, IQR 2-6). While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. Monitoring social contacts is an important indicator to estimate the possible impact of government interventions on social contacts and the COVID-19 spread in the coming months.

HPV vaccination and sexual behaviour in healthcare seeking young women in Luxembourg.

INTRODUCTION: Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Despite recommendations for HPV vaccination of young women from health authorities, parental concerns were raised whether vaccination could induce unsafe sexual behaviour in young women. Therefore, the primary aim of this study was to investigate if HPV vaccination in healthcare seeking adult women in Luxembourg was associated with unsafe sexual behaviour. METHODS: Seven hundred twenty-nine women (mean age = 22.5; range 18-43 years) were recruited either at Luxembourg family planning centres or at private gynaecology practices. All participants completed a questionnaire on vaccination status and sexual behaviour. Poisson and logistic regressions were used to study the association between sexual behaviour and vaccination status (N = 538). Both models were restricted to women younger than 26 years, since the first cohort being vaccinated would be 25 years old at the time of sampling. Assortativity of sexual mixing by age was also assessed for further transmission modelling for women <30 years reporting age of last/current sexual partner (N = 649). Women older than 29 years were excluded from the assortativity analysis due to restricted sample size. RESULTS: In total, 386/538 (71.8%) of participants reported receiving HPV vaccine. Vaccination uptake significantly varied by nationality and was higher in Portuguese 112/142 (78.9%) and in Luxembourgish 224/313(71.6%) residents, and lower in residents of other nationalities 50/83 (60.2%) (p = 0.011). HPV vaccination was not associated with unsafe sexual behaviour such as shorter relationship duration with current or last sexual partner (odds ratio (OR) = 1.05, 95% CI [0.94-1.16]), younger age of sexual debut (OR = 1.00, 95% CI [0.88-1.14]), increased number of lifetime sexual partners (OR = 0.95, 95% CI [0.87-1.03), higher age difference with sexual partner (OR = 1.01, 95% CI [0.95-1.08]), condom use (OR = 0.97, 95% CI [0.60-1.56]), nor with other factors like smoking (OR = 0.73, 95% CI [0.47-1.15]) and nationality. HPV vaccination was only associated with younger age (OR = 0.84, 95% CI [0.75-0.94]). Relationship duration, age of sexual debut, age difference with sexual partner, smoking, age and non-Portuguese foreign nationality were predictors of number of lifetime sexual partners. Assortativity analysis revealed that young women chose sexual partners who were 2.3 years older on average. CONCLUSIONS: Our study found no association between unsafe sexual behaviour and HPV vaccination.

Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg.

BACKGROUND: In Luxembourg, the human papillomavirus (HPV) vaccination program introduced in 2008, provided either bivalent (BV) or quadrivalent (QV) vaccines to girls aged 12-17 years. Here, we estimate the effectiveness of BV and QV vaccines combined and separately in reducing type-specific HPV prevalence eight years after the introduction of the vaccination program. METHODS: A cross-sectional prevalence study was conducted among women aged 18-29 years in 2015-2017. Seven hundred sixteen participants were recruited at family planning centres or private gynaecology practices in Luxembourg. Vaccination records were verified in the social security database. Cervical samples were tested using the Anyplex II HPV28 assay. Vaccine effectiveness was estimated using logistic regression. RESULTS: In total, 363/716 (50.7%) participants were HPV positive with any HPV and 209/716 (29.2%) with carcinogenic HPV genotypes. HPV vaccination offered high protection against HPV16/18 (adjusted odds ratio (AOR) = 0.13; 95% CI 0.03-0.63), HPV6/11 (AOR = 0.16; 95% CI 0.05-0.48) and cross-protection against HPV31/33/45 (AOR = 0.41; 95% CI 0.18-0.94). The AORs were generally enhanced when only considering vaccination before sexual debut corresponding to AORs: 0.05 (95% CI 0.00-0.88), 0.08 (95% CI 0.02-0.36) and 0.20 (0.06-0.65) against HPV16/18, HPV6/11 and HPV31/33/45, respectively. We observed significant protection against carcinogenic genotypes included in nonavalent vaccine for BV (AOR = 0.29; 95% CI 0.13-0.67), but not for QV (AOR = 0.81; 95% CI 0.47-1.40) (heterogeneity Chi2 P = 0.04). CONCLUSIONS: Our study suggests high effectiveness of HPV vaccination against HPV6/11, HPV16/18 and a cross-protection against HPV31/33/45. Vaccination effectiveness was slightly higher for women vaccinated before sexual debut.

Human papillomavirus vaccination coverage in Luxembourg - Implications of lowering and restricting target age groups.

BACKGROUND: In Luxembourg, a national Human Papillomavirus (HPV) vaccination programme was introduced in 2008, targeting 12-17 year old girls offering a choice of bivalent or quadrivalent vaccine free of charge. In 2015, the programme was changed offering the bivalent vaccine only to 11-13 year old girls. The aim of this study was to evaluate the HPV vaccination coverage, to assess the impact of age target changes and compare vaccination coverage to other European countries. METHODS: Anonymous HPV vaccination records consisting of individual vaccine doses obtained free of charge in pharmacies between 2008 and 2016 were extracted from the Luxembourgish Social Security database. Additional aggregate tables by nationality and municipality were analysed. RESULTS: Of the target cohort of 39,610 girls born between 1991 and 2003 residing in Luxembourg, 24,550 (62.0%) subjects obtained at least one dose, 22,082 (55.7%) obtained at least two doses, and 17,197 (43.4%) obtained three doses of HPV vaccine. The mean age at first dose was 13.7 years during 2008-14 and 12.7 years in 2016 after the age target change. Coverage varied significantly by nationality (p < 0.0001): Portuguese (80%), former Yugoslavs (74%), Luxembourgish (54%), Belgian (52%), German (47%), French (39%) and other nationalities (51%). Coverage varied also by geographical region, with lower rates (<50%) noted in some Northern and Central areas of Luxembourg (range: 38% to 78%). CONCLUSION: Overall HPV vaccination coverage in Luxembourg is moderate and varied by nationality and region. The policy changes in 2015 did not have a substantial impact except lowering age at initiating vaccination. Options to improve coverage deserve further investigation.

Complete Genome Sequence of a Novel Human Gammapapillomavirus Isolated from a Cervical Swab in Luxembourg.

A novel human papillomavirus genotype was detected in a cervical swab specimen by next-generation sequencing after rolling circular amplification. It was fully cloned and characterized. The L1 open reading frame showed 77% nucleotide similarity with the closest genotype, HPV101, belonging to the gamma-6 species.

Introduction of liquid-based cytology and human papillomavirus testing in cervical cancer screening in Luxembourg.

BACKGROUND: In 2014, liquid-based cytology with HPV triage replaced conventional cytology. The aim of our study was to compare conventional and liquid-based cytology (LBC), estimate the prevalence of abnormal cervical cytology and high risk HPV (hrHPV) infection and their correlation, among screened women in Luxembourg. METHODS: Between the first January 2013 and 31st December 2015, 315,868 cervical samples from 150,815 women (mean age 42.2 years) were investigated by the national cytology laboratory. Slides were prepared and screened according to European Guidelines. All cytological results were classified according to the Bethesda 2001 system terminology. RESULTS: The prevalence of abnormal cervical lesions was as follows: atypical squamous cells of undetermined significance (ASC-US), 1.3%; low-grade squamous intraepithelial lesion (LSIL), 1.9%; high-grade squamous intraepithelial lesion (HSIL), 0.4%. The detection rate of cytological lesions was significantly higher with LBC than with conventional cytology. Based on 11,838 samples with concomitant cytology and HPV testing, hrHPV was detected in 9.5, 45.3, 70.0, and 92.6% of women with negative cytology, ASC-US, LSIL, and HSIL, respectively. CONCLUSION: More cervical lesions were identified using LBC compared to conventional cytology. HrHPV infection was correlated with the severity of intraepithelial lesions. The current findings provide important information to evaluate the prevention of cervical cancer in Luxembourg and for monitoring the future impact of HPV vaccination. Diagn. Cytopathol. 2017;45:384-390. © 2017 Wiley Periodicals, Inc.

Associations of genetic variants for adult lipid levels with lipid levels in children. The Generation R Study.

Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these variants already affected lipid concentrations in a large group of 2,645 children with a median age of 6.0 years (95% range 5.7-7.3 years) from the population-based Generation R Study. Twenty-eight SNPs associated with TGs, 39 SNPs associated with total cholesterol (TC), 28 SNPs associated with LDL cholesterol (LDL-C), and 56 SNPs associated with HDL cholesterol (HDL-C) were analyzed individually and combined into genetic risk scores (GRSs). All risk scores were associated with their specific outcomes. The differences in mean absolute lipid and lipoprotein values between the 10% of children with the highest lipid or lipoprotein GRS versus the 10% with the lowest score were 0.28, 0.25, 0.32, and 0.30 mmol/l for TGs, TC, LDL-C, and HDL-C, respectively. In conclusion, we show for the first time that GRSs based on 157 SNPs associated with adult lipid concentrations are associated with lipid levels in children. The genetic background of these phenotypes at least partly overlaps between children and adults.

Analytical performance evaluation of Anyplex II HPV28 and Euroarray HPV for genotyping of cervical samples.

Analytically accurate human papillomavirus (HPV) genotyping methods are required to assess the impact of HPV vaccination. The aim of this study was to evaluate the analytical performance of Anyplex II HPV28 (Seegene, Korea) and Euroarray HPV (Euroimmun, Germany) genotyping kits, for conducting a future HPV vaccine efficacy monitoring study in Luxembourg. A total number of 150 cervical swabs were collected from women with mean age 31.4 years. Agreements for detecting any HPV between Aptima/Anyplex (88.0%) and Aptima/Euroarray (90.7%) were similar. Agreement of Anyplex/EuroArray with Aptima was higher for Genotypes 16, 18 or 45 than for the other 11 HPVs. The average number of HPV genotypes detected per sample was similar with 2.6 and 2.5, for Anyplex and EuroArray, respectively. In conclusion, Anyplex and Euroarray showed high agreement in general and in particular for detecting genotypes contained in HPV vaccines.

Landscape Complexity in the Caucasus Impedes Genetic Assimilation of Human Populations More Effectively than Language or Ethnicity.

The analyses of 15 autosomal and 23 Y-chromosome DNA single-tandem-repeat loci in five rural populations from the Caucasus (four ethnically Georgian and one ethnically Armenian) indicated that two Georgian populations, one from the west and the other from the east of the Greater Caucasus Mountains, were both patrilineally and autosomally most differentiated from each other, and the other populations of Georgians and Armenians held an intermediate position between those two. This pattern may be due to human dispersal from two distinct glacial refugia in the last glacial period and the early Holocene, followed by less gene flow among the populations from the Greater Caucasus than among those from the rest of the Caucasus, where the populations have undergone substantial admixture in historical time. This hypothesis is supported by a strong correlation between genetic differentiation among the populations and landscape permeability to human migrations as determined by terrain ruggedness, forest cover, and snow cover. Although geographic patterns of autosomal and Y-chromosome DNA are not fully concordant, both are influenced by landscape permeability and show a similar east-west gradient. Our results suggest that this permeability was a stronger factor limiting gene flow among human populations in the Caucasus than were ethnic or linguistic boundaries.