Severien Van Keer

Lineages and sublineages of high-risk human papillomavirus types associated with cervical cancer and precancer: a systematic review and meta-analysis

Abstract Background Infection with high-risk types of the human papillomavirus (HPV) is known to cause cervical cancer. Cervical cancer risk varies greatly by genotype, which is therefore used in screening algorithms. An extensive amount of research has also focused on the differential pathogenicity of high-risk HPV subtypes called lineages and sublineages (respectively 1.0%-10% and 0.5%-1.0% genetic difference), albeit with inconclusive and contradictory results. Therefore, the topic is systematically reviewed for the first time to determine whether the clinical use of (sub)lineage detection is supported. Methods Three databases for health sciences (PubMed, Web of Science, and Scopus) were searched for relevant papers. Meta-analysis was performed for HPV16-positive patients with cervical cancer and healthy participants using random effects models. Results The search yielded 1535 records, and 93 papers were included after the selection process. Although some trends in disease association were detected, 46 studies did not find statistically significant differences between (sub)lineages in individuals with and without cervical disease. Additionally, the reports are heterogeneous in terms of study design and often characterized by a small sample size. The meta-analysis found odds ratios of 2.2 (95% CI = 1.49 to 3.15) for HPV16 A4; 2.1 (95% CI = 1.25 to 3.40) for HPV16 D; and 0.48 (95% CI = 0.33 to 0.68) for HPV16 A1-3 with statistically significant heterogeneity (38%-77%). Conclusion This systematic review and meta-analysis provide an overview of the high-risk types of HPV (sub)lineages and association with cervical disease. Although some (sub)lineages marginally correlate with cervical malignancy, there is great variability. Unlike genotyping, this study demonstrates insufficient association between high-risk HPV (sub)lineages and cervical malignancy for clinical use to date.

Accuracy of Liferiver HarmoniaHPV and VenusHPV Assays on Urine and Vaginal Self‐Samples

ABSTRACT In this report, the clinical performance of Liferiver HarmoniaHPV and Liferiver VenusHPV was evaluated under the VALHUDES framework. Five hundred and twenty‐three women collected first‐void urine (FVU) with Colli‐Pee and vaginal samples with Evalyn Brush or Qvintip. Cervical samples were taken with the Cervex Brush by a clinician. Both vaginal and cervical samples were resuspended in 20 mL ThinPrep. Triplet samples from 499 women were tested with HarmoniaHPV and VenusHPV tests. The clinical accuracy of HarmoniaHPV did not differ in FVU and vaginal self‐samples versus cervical samples. The relative sensitivity for CIN2+ on FVU and vaginal samples was 0.95 [95% CI 0.89–1.02] and 0.95 [95% CI 0.88–1.02], respectively. Relative specificity for < CIN2 was 0.95 [0.86–1.04] on FVU and 0.93 [0.86–1.01] on vaginal samples. VenusHPV demonstrated lower sensitivity on both self‐sample types, whereas the specificity was similar to cervical samples. Post‐hoc adjustment of the VenusHPV C t ‐values improved sensitivity (ratio FVU/cervical = 0.94 [95% CI 0.88–1.00]; ratio vaginal/cervical = 0.96 [95% CI 0.92–1.01]) without compromising specificity (ratio FVU/cervical = 1.00 [0.92–1.09]; ratio vaginal/cervical = 0.95 [95% CI 0.88–1.02]) on both self‐samples. In conclusion, HarmoniaHPV and VenusHPV tests demonstrated similar clinical accuracy on FVU and vaginal self‐ versus cervical samples, although VenusHPV test required cut‐off optimization.

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

Abstract 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.

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

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. 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. 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. 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 <CIN2 (ratio 0.92; 95% CI: 0.84-0.996) compared to cervical samples. HPV test agreement between sample pairs expressed as Cohen's Kappa (κ) was moderate to excellent for overall hrHPV and individual genotypes (or groups) (κ=0.56-0.85). BD Onclarity HPV Assay on first-void urine has similar clinical sensitivity and somewhat lower specificity to detect cervical precancer to testing on clinician-collected cervical samples.

Clinical Performance of the RealTi m e High Risk HPV Assay on Self-Collected Vaginal Samples within the VALHUDES Framework

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.

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

Equivalent Clinical Accuracy of Human Papillomavirus DNA Testing Using Cobas 4800 and 6800 Human Papillomavirus Systems in Paired Urine and Cervical Samples

The use of urine for cervical cancer screening is gaining international attention, although more data on the relative clinical accuracy of validated human papillomavirus (HPV) DNA tests on urine versus cervical samples are needed. This study primarily seeks to evaluate the clinical performance of Roche cobas 4800 and 6800 HPV Systems in first-void urine, collected at home, compared with clinician-collected cervical samples. Paired first-void urine (index test) and cervical samples (comparator test) from 499 females enrolled at five Belgian colposcopy clinics were analyzed with cobas HPV Systems. Colposcopy and histology of biopsies were used as reference test (trial registration number: NCT03064087). Sample processing protocols and clinical thresholds proposed by the manufacturer for cervical samples were also applied for first-void urine. In the total study population, HPV testing on first-void urine was similarly sensitive [ratio

Clinical and Analytical Evaluation of the Abbott Alinity m HR HPV Assay in a New Generation First‐Void Urine Collector

ABSTRACTUrine‐based self‐sampling approaches can simplify cervical screening programs whilst increasing response. This study reports on the performance of Abbott Alinity m HR HPV on urine, self‐collected at home using a new generation first‐void urination device that is suitable for postal delivery (Novosanis Colli‐Pee Small Volumes). First‐void urine and paired cervical samples from 297 females attending colposcopy (age 25–65, NCT04530201) were analysed for the presence of Human Papillomavirus (HPV) DNA. Cervical disease was confirmed by colposcopy and/or histology. HPV testing on first‐void urine was less sensitive for high‐grade cervical intraepithelial neoplasia (CIN2 +; ratio 0.91; 95% CI: 0.83–0.99), though equally specific (&lt; CIN2; ratio 1.04; 95% CI: 0.92–1.19) compared to cervical samples at the manufacturer established cut‐off for cervical samples. Adjusting the cut‐off for first‐void urine improved sensitivity for CIN2+ (ratio 0.96; 95% CI: 0.90–1.03), whilst maintaining equal specificity compared to cervical samples (ratio 1.00; 95% CI: 0.88–1.14). Cohen's kappa agreements of HPV outcomes between sample pairs were good to excellent at both cut‐offs (range: 0.64–0.85). Using the HPV test's adjusted cutoff for first‐void urine, no difference in clinical sensitivity or specificity was observed between first‐void urine and cervical samples. These data highlight the importance of evaluating self‐sample‐specific cut‐offs for HPV assays, previously validated on cervical samples.

Self-collected Vaginal and Urine Samples in HIV-positive Women

This study assesses topics as Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV), and cancer screening methods. The focus will be on evaluating feasibility of implementing novel cancer screening modalities in a low-resource setting in Guinea-Bissau and further to estimate the prevalence of the precancerous virus HPV amongst women living with HIV. In the study the investigators will collect urinary and vaginal self-samples for HPV testing, and further evaluate the feasibility of implementing the devices as screening modalities through questionnaires given to the women.

Validation of Human Papillomavirus Assays and Collection Devices for Self-samples and Urine Samples

The VALHUDES study is a Diagnostic Test Accuracy study that aims to document the clinical accuracy of hrHPV testing on urine samples, collected under standardised and optimised conditions, and on two types of vaginal self-samples and compare results with those from matching samples taken by a clinician.