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.

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

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. 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. 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). 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.

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.

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.