Alex Vorsters

Case studies on the progress of cervical cancer screening programs in Bhutan, India, and Türkiye

International stakeholders gathered in New Delhi, India, in December 2022 to share experiences on human papillomaviruses (HPV) prevention and control strategies. As part of a supplementary publication from the meeting proceedings, this paper describes secondary HPV prevention strategies highlighting the varying degrees of progress and challenges through case studies from Bhutan, India, and Türkiye. India has implemented national screening guidelines, primarily using visual inspection with acetic acid (VIA), but achieving a low coverage rate of 1.9% (2022). In contrast, Bhutan and Türkiye have redesigned and established HPV-based cervical screening programs targeting women aged 30-65, achieving 77% (2022) and 95% (2019) coverage among women ever screened, respectively. Lessons learned include utilising patient health information management systems, analysing optimal context-specific HPV testing strategies and ensuring use and continuous supply of clinically validated HPV tests.

Overview of CHIC symposia series: Summary of Africa and South Asia symposia

This article presents an overview of the main challenges and lessons learned that were presented during the symposia organized by the Coalition to Strengthen the HPV Immunization Community (CHIC) in Africa and South Asia in 2022. Discussions at these meetings revolved around introduction, planning, implementation, and sustainability of HPV prevention and control programmes, with a particular focus in HPV immunisation, as well as cervical cancer screening in South Asian countries. This article also discusses the recently endorsed off-label single-dose HPV vaccination schedule and its potential impact on programme delivery and access. Furthermore, it highlights the importance of intersectional collaboration, effective communication and advocacy strategies, and the need for robust health information systems. Some of the critical factors identified for reducing the burden of cervical cancer in low- and middle-income countries (LMICs) included strategies for increasing access and coverage, addressing vaccine hesitancy, and building capacity among health care providers. The symposia emphasized the importance of face-to-face interactions for collaboration and decision making, with live translation services enabling full participation by stakeholders from diverse backgrounds. The paper concludes with a call for continued collaboration to make progress in reducing the burden of cervical cancer in LMICs.

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.

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.

Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: an Update for the Laboratory

Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most prominent types. HPV testing is performed in laboratory settings for various applications of a clinical, epidemiological, and research nature using a range of clinical specimens collected by clinicians or by individuals (self-collected specimens).

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.

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