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 200814 and 12.7 years in 2016 after the age target change. Coverage varied significantly by nationality (p < 0.0001): Portuguese (80%), former Yugoslays (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

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

Impact of human papillomavirus vaccination in Luxembourg

Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide and the principal cause of cervical cancer. The etiological link between HPV and cervical cancer has led to development of large and successful population-based prevention programs, such as screening and vaccination. The main purpose of this PhD thesis was to evaluate cervical cancer screening and human papillomavirus (HPV) vaccination in Luxembourg and provide local evidence based data to policy makers for helping to improve prevention programs. Analysis of cervical cancer screening data from the national cytology laboratory showed that screening coverage was high reaching 75%. As expected, HPV infection was significantly associated with severity of abnormal cytological lesions. Second, HPV vaccination coverage and effectiveness were evaluated using social security records. The moderate HPV vaccination coverage in Luxembourg was significantly associated with nationality and showed patterns of spatial pockets with low vaccination coverage. To estimate vaccination effectiveness a cross-sectional prevalence study in 716 women was conducted in family planning centres. HPV vaccination with bivalent or quadrivalent vaccines had a significant impact on HPV type-specific prevalence and distribution in young women. Whereas both vaccines demonstrated high effectiveness against HPV types 16 and18, the bivalent vaccine showed better cross-protection against some HPV types not included in the vaccine. Additionally, we discovered of a novel genotype of the gamma-6 species in a cervical sample, based on next generation sequencing. After cloning, the genotype was confirmed by the WHO HPV reference centre in Sweden as type HPV226. To conclude, results from my PhD suggest that both screening and vaccination programs will lead to lower incidence of cervical cancer in Luxembourg

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

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

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 forHPVvaccination 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 D 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 D 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 D649). 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 D 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)D1.05, 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