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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.

ABSTRACTHuman papillomavirus (HPV) vaccines, primarily relying on neutralizing antibodies, have proven highly effective. Recently, HPV-specific antibodies have been detected in the female genital tract secretions captured by first-void urine (FVU), offering a minimally invasive diagnostic approach. In this study, we investigated whether HPV16-specific antibodies present in FVU samples retain their neutralizing capacity by using pseudovirion-based neutralization assays. Paired FVU and serum samples (vaccinated n = 25, unvaccinated n = 25, aged 18–25) were analyzed using two orthogonal pseudovirion-based neutralization assays, one using fluorescence microscopy and the other using luminescence-based spectrophotometry. Results were compared with HPV16-specific IgG concentrations and correlations between neutralizing antibodies in FVU and serum were explored. The study demonstrated the presence of neutralizing antibodies in FVU using both pseudovirion-based neutralization assays, with the luminescence-based assay showing higher sensitivity for FVU samples, while the fluorescence microscopy-based assay exhibited better specificity for serum and overall higher reproducibility. High Spearman correlation values were calculated between HPV16-IgG and HPV16-neutralizing antibodies for both protocols (rs: 0.54–0.94, p < .001). Significant Spearman correlations between FVU and serum concentrations were also established for all assays (rs: 0.44–0.91, p < .01). This study demonstrates the continued neutralizing ability of antibodies captured with FVU, supporting the hypothesis that HPV vaccination may reduce autoinoculation and transmission risk to the sexual partner. Although further protocol optimizations are warranted, these findings provide a foundation for future research and larger cohort studies that could have implications for the optimal design, evaluation, and implementation of HPV vaccination programs.

Background: First-void urine (FVU) provides a non-invasive method for collecting a wide range of biomarkers found in genital tract secretions. To optimize biomarker collection in FVU, this study investigated the impact of naturally present and supplemented precipitating agents: uromodulin (UMOD) and polyethylene glycol (PEG), on the concentration of human papillomavirus (HPV) pseudovirions (PsV), cell-free DNA (cfDNA), and cellular genomic DNA (gDNA) through centrifugation. Methods: FVU samples from ten healthy female volunteers, along with a control sample, were spiked with seal herpesvirus 1 (PhHV-1) DNA, HPV16 plasmid DNA, and HPV16 PsV with an enhanced green fluorescent protein (EGFP) reporter. The samples were subjected to various concentration protocols involving PEG precipitation, low-speed centrifugation (5 min at 1000×g), and medium-speed centrifugation (1 h at 3000×g). Subsequently, quantitative PCR (qPCR) was used to assess cellular and cell-free glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA, cell-free PhHV-1 and HPV16 DNA, and PsV (EGFP) DNA. In addition, UMOD levels were measured. Results: The findings revealed that PEG significantly increased the concentration of cfDNA and gDNA in the pellet after centrifugation, with the most pronounced effect observed for cfDNA. Moreover, low-speed centrifugation without PEG effectively depleted cellular gDNA while preserving cfDNA in the supernatants. Pseudovirions were consistently pelleted, even with low-speed centrifugation, and a positive but not significant effect of PEG on PsV (EGFP) DNA yield in the pellet was observed. Additionally, a significant correlation was observed between UMOD and GAPDH, HPV16, and PsV (EGFP) DNA quantities in the pellet. Furthermore, large variations among the FVU samples were observed. Conclusions: With this study, we provide novel insights into how various biomarker precipitation protocols, including both the properties of FVU and the use of PEG as a precipitating agent, influence the concentration of cfDNA, cellular gDNA, and pseudovirions.

BackgroundHuman papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are.MethodsWe conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail.Main resultsFrom 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents.ConclusionThe evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

ABSTRACTProphylactic vaccines are efficacious in preventing Human Papillomavirus (HPV) infection and subsequent cervical intraepithelial neoplasia (CIN), cervical cancer, other anogenital cancers, and anogenital warts. Female sex workers (SW) are at increased risk of acquiring sexually transmitted infections, including HPV. There are several reasons to offer HPV vaccination to SW: they are at high risk for HPV and often unvaccinated, and the immunogenicity of the vaccine is also excellent in previously HPV exposed women. Furthermore, women with disease caused by HPV may still benefit from vaccination. The efficacy of vaccinating mid-adult women (26–44 years old) against persistent HPV infection and CIN2+ is good. Although an SW may have been infected or exposed to HPV, she may not have been exposed to all vaccine-included hrHPV types. Vaccination induces mucosal immunity via the production of neutralizing antibodies on the surface of the female genital tract, thus preventing potential transmission to clients.Nevertheless, some considerations argue against offering vaccination to SWs. Current vaccines are only prophylactic and as such, do not affect current HPV infections. Women who have previously cleared HPV infections, may do so again and thus not need vaccination. Fewer SW might be naïve to HPV-types than currently thought. HPV vaccination has probably no effect on latent infections. Vaccinating sometime after sexual debut could be too late, as infections have already occurred.Taken together, some data suggest that vaccination of SW may offer health benefits, also for the community, but sufficient evidence is lacking. In certain cases, HPV vaccination of SW may be recommended. Evidence-based, public health decisions concerning vaccination of SW are challenging and could be facilitated with more research in this high-risk group.

The Human Papillomavirus Prevention and Control Board brought together experts to discuss optimizing HPV vaccination and screening programs.

ABSTRACTGP5+/6+-based PCR followed by reverse line blot hybridization (GP5+/6+RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5+/6+RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5+/6+RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5+/6+RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5+/6+RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5+/6+RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5+/6+RLB than for those negative for the same type by GP5+/6+RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5+/6+RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5+/6+RLB, suggesting the existence of masking effects due to competition for GP5+/6+ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination.

The accuracy of hrHPV testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALHUDES framework. We recruited 523 women in five Belgian colposcopy clinics, of which 483 (median age 40 years; IQR 31-49) were included in the main analysis (226 collected with Evalyn Brush and 257 with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard.

ABSTRACTLow-and-middle-income countries (LMICs) experience a high burden of cervical cancer. The human papillomavirus (HPV) vaccine prevents high-risk strains of HPV that cause cervical cancer; however, the integration of HPV vaccines into national immunization programs within many LMICs has been suboptimal. Our study evaluated key factors that drive the decision-making process for the implementation of HPV vaccine programs in LMICs. Stakeholder analysis and semi-structured in-depth interviews were conducted with national and global stakeholders. Interview data were analyzed through qualitative descriptive methods. Findings from our study revealed the decision-making process for HPV vaccines requires the involvement of multiple institutions and stakeholders from national and global levels, with decision-making being a country-specific process. Partner considerations, locally driven processes, availability of data, and infrastructure and resource considerations were found to be critical factors in the decision-making process. Future programs should evaluate the best approaches for investing in initiatives to enhance coordination, ensure vaccine introduction is locally driven, increase the availability of data needed for decision-making, and equip countries with the necessary resources to guide country decision-making in the face of increasingly complex decision-making environments.

This review offers an update on hepatitis A, B and E vaccines based on relevant literature published in 2011–2012. Hepatitis A and B vaccines have been commercially available for years; however, the development of the hepatitis E vaccine is still facing some challenges.

In the nine years since the Global Advisory Group of the Expanded Programme on Immunisation (WHO) set 1997 as the target for integrating hepatitis B vaccination into national immunisation programmes worldwide, 129 countries have included hepatitis B vaccine as part of their routine infant or adolescent immunisation programmes (June 2001). By the end of 2002, 41 out of the 51 countries of the WHO European Region will be implementing universal hepatitis B immunisation. The rewards of effective implementation of the programmes in countries that started 10 years ago are becoming apparent; and their success offers an exemplary model for other countries. Some other countries, however, have difficulties to incorporate hepatitis B vaccine into universal childhood immunisation programmes, because of major economic constrains and the inability to procure a constant vaccine supply. The next decade will be characterised by expanded use of hepatitis B vaccines and the increasing efforts to sustain vaccine programmes and make the vaccine available to those countries and regions that cannot afford it. In Europe, as well as in the rest of the world, work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to eradicate hepatitis B. J. Med. Virol. 67:433–439, 2002. © 2002 Wiley‐Liss, Inc.

Background: Interventions to reach women who do not participate regularly in screening may reduce the risk of cervical cancer. Self-collection of a vaginal specimen has been shown to increase participation. The relative clinical accuracy of human papillomavirus (HPV) testing on first-void urine (with Colli-Pee) and on vaginal self-samples versus on cervical clinician-collected samples is being investigated in the VALHUDES trial. The current study assesses attitudes and experiences regarding self-sampling among women enrolled in VALHUDES. Methods: Questionnaires from 515 women (age 25–64 years [N= 498]; &lt; 25 [N= 10], age ≥ 65 [N= 3], enrolled between December 2017 - January 2020) referred to colposcopy because of previous cervical abnormalities and enrolled in VALHUDES (NCT03064087) were analysed. Results: Of the 515 participants, nearly all women confirmed that self-sampling may help in reaching under-screened women (93%). Nevertheless, 44% of the participants stated before starting collection that a clinician-collected sample is more effective than a self-collected sample. After self-sampling, the large majority of women (> 95%) declared that instructions for self-collection were clear, that collection was easy, and that they were confident about having performed the procedure correctly, for both urine and vaginal collection. However, a proportion of women found self-sampling unpleasant (9.5% [49/515] for urine collection; 18.6% [96/515] and 15.5% [80/515] for vaginal sampling with cotton swabs or plastic brushes, respectively). For their next screening round, 57% would prefer self-sampling whereas 41% opted for collection by a clinician. Among women preferring self-sampling, 53% would choose for urine collection, 38% for vaginal self-collection and 9% had no preference. Age did not modify preferences. Conclusion: We conclude that both urine and vaginal self-sampling are well accepted by women, with a preference for urine sampling. Although the large majority of women are confident in their ability to perform self-sampling, four to five over ten women preferred specimen collection by a clinician. Trial registration: The study VALHUDES was registered in ClinicalTrials.gov(identifier: NCT03064087).

ABSTRACTWhen considering what the scientific evidence is for the potential added value to offer HPV vaccines to sex workers, not only its potential role for female sex workers should be examined, but its role for all those who conduct sex work. Our initial paper looked at the evidence in terms of HPV vaccine immunogenicity, efficacy, effect on transmission, induction of mucosal immunity, and not at implementation. Brown and Cabral considered our omission to address the aspects of implementation an ‘academic mistake’. We disagree; implementation aspects are complex and require analyses of multiple barriers, and how to address these. It only makes sense to discuss these if there is scientific evidence for its implementation; otherwise offering the vaccine is not useful.

The Human Papillomavirus (HPV) Prevention and Control Board convened a meeting in Bucharest, Romania (May 2018), to discuss the role of healthcare providers (HCPs) in prevention programs, with a focus on HPV vaccination and cervical cancer screening. International and local experts discussed the role that HCPs can play to increase the uptake of HPV vaccine and screening. Experts recommended: 1) increasing HCP norms of getting vaccinated; 2) training providers to make effective recommendations; 3) making culturally appropriate materials available, in local languages; and 4) centralizing and coordinating education and information material, to direct both HCPs and the general public to the best material available.

Human papillomavirus (HPV) infects and propagates in the cervical mucosal epithelium. Hence, in addition to assessing systemic immunity, the accurate measurement of cervical immunity is important to evaluate local immune responses to HPV infection and vaccination. This review discusses studies that investigated the presence of infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions (CVS).