Assessment of Acceptability and Determinants of Uptake and Schedule Completion of Human Papillomavirus (HPV) Vaccine by 25 to 45 Years Old Women in Slovenia.

HPV immunization programs are mainly focused on girls and boys, but adult women and men could also benefit from vaccination. A multinational CoheaHr-WP4 study investigated the acceptability of HPV vaccination among 25-45 years old women. A total of 607 women from Slovenia participated in the study, and 49.6% (301/607) agreed with HPV vaccination, with a significant difference (p < 0.0001) between the two centers. Non-vaccinated women had a higher education (p = 0.0068) and were more frequently in a committed relationship or married (p = 0.01). The most trusted source of medical and vaccination information was healthcare providers (55.2%). The main reasons for vaccine acceptance were protection against HPV-related disease (93.4%), severity of preventable diseases (82.7%), HPV vaccine safety (66.8%), free HPV vaccine availability (62.8%), and the existence of vaccination recommendations (55.5%). The main reasons for refusing vaccination were the need for additional vaccine-related information (31.4%) and vaccine safety concerns (29.4%). To increase vaccine coverage, information about the benefits and safety of HPV vaccination must be widely disseminated to all health professionals and the general public. We are convinced that the knowledge obtained in this study can be reliably applied to other countries in the region that lack such information and have a very high cervical cancer burden.

Real-Life Head-to-Head Comparison of Performance of Two High-Throughput Automated Assays for the Detection of SARS-CoV-2 RNA in Nasopharyngeal Swabs: The Alinity m and cobas 6800 SARS-CoV-2 Assays.

The Alinity m (Abbott Molecular, Des Plaines, IL) automated molecular analyzer allows continuous loading of samples and sample-to-result molecular detection of several microorganisms. The detection of SARS-CoV-2 by the Alinity m was compared with that of the cobas 6800 (Roche Molecular Systems, Branchburg, NJ; standard comparator) in a manufacturer-independent clinical evaluation on 2157 consecutive nasopharyngeal swab samples. Valid initial results on Alinity m and cobas 6800 were obtained from 2129 (98.7%) and 2157 (100%) samples, respectively. The overall percent agreement (95% CI) was 98.3% (2092/2129 [97.6%-98.7%]); positive percent agreement, 100% (961/961 [99.6%-100%]); negative percent agreement, 96.8% (1131/1168 [95.7%-97.7%]); and high κ value, 0.965 (0.954-0.976). There were 37 discordant results on Alinity m and, based on discordant analyses, including previous and/or follow-up PCR results, 22 could be considered analytically true positive with high probability. Due to a lack of additional information and an inability to perform repeated/further testing, the status of the remaining 15 discordant results remained unresolved. The throughput of the two analyzers was compared using testing on 564 samples in parallel across two 8-hour shifts in clinical practice. The turnaround times were compared using processing of 94 routine samples in parallel on each working day for 5 consecutive days. The two analyzers showed similar performance, with certain differences that have potential importance in some laboratory settings.

Usefulness of COVID-19 screen-and-test approach in pregnant women: an experience from a country with low COVID-19 burden.

OBJECTIVES: Information on the usefulness of screen-and-test strategies of pregnant women for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is lacking. METHODS: We retrospectively reviewed the Ljubljana Maternity Hospital database and searched for pregnant women, who were admitted to the hospital between March 15 and May 16, 2020, for a planned procedure or hospitalization. Their medical records were examined and SARS-CoV-2 test results were retrieved. RESULTS: During the two-month period analyzed, there were a total of 265 scheduled admissions of pregnant women to our hospital. Two hundred two (76.2%) were tested for SARS-CoV-2 1 day prior to admission. All tested negative for SARS-CoV-2 RNA, regardless of having coronavirus disease 2019 (COVID-19)-compatible signs or symptoms (n=28) or not (n=174). CONCLUSIONS: In a population with a low SARS-CoV-2 burden, usefulness of universal testing of pregnant women before admission to the hospital is limited. We recommend that obstetric units in regions with low SARS-CoV-2 burden enforce rational use of personal protective equipment and diligent screening protocols using targeted questionnaires, whereas SARS-CoV-2 laboratory testing should be performed only in screen-positives: those with high clinical suspicion of COVID-19 and/or suspected epidemiological history.

Histomorphologic assessment and distribution of high-risk human papillomavirus (HPV) types in cervical high-grade squamous intraepithelial lesions with unusual histomorphologic features.

In rare cases, equivocal histomorphology ('deceiving dysplasia') does not allow immediate diagnosis of cervical high-grade squamous intraepithelial lesion (HSIL). We studied whether these cases are correlated with specific high-risk human papillomavirus (hr HPV) types. During 2011-2017, 39 cases of p16-positive cervical tissue biopsies with unusual ('deceiving') dysplastic histomorphology were identified and matched with the same number of controls (typical HSIL samples). Histomorphological characteristics were reviewed blindly and HPV testing was performed using the clinically validated RealTime test (Abbott) and Anyplex HPV 28 (Seegene). HPV 16 and HPV 31 were the two most frequent HPV types in both groups, although minimum, proportional, hierarchical and any etiological attribution estimates for HPV 16 were significantly lower in the deceiving group (13.2%, 21.3%, 23.7% and 23.7%) than in the control group (32.4%, 48.1%, 48.6% and 48.6%). In addition, the distribution of other hr HPV types differed between the two study groups, with five HPV types (HPV 56, 58, 59, 73 and 82) detected only in the deceiving group. Histomorphologic review of both groups (regardless of HPV type) confirmed significant differences in nuclear atypia, maximum lesion thickness and cellularity, although these were diminished when cross-comparisons between HPV16/18 and non-HPV16/18 cases pooled from both study groups were evaluated. Different attribution estimates for HPV 16, HPV 16/18 and non-16/18 hr HPV types in deceiving and control groups were observed, in particular for HPV 16. However, an unusual (deceiving) histomorphology may also depend on unknown HPV-related molecular changes.

Improving preparedness to respond to cross-border hepatitis A outbreaks in the European Union/European Economic Area: towards comparable sequencing of hepatitis A virus.

IntroductionSequence-based typing of hepatitis A virus (HAV) is important for outbreak detection, investigation and surveillance. In 2013, sequencing was central to resolving a large European Union (EU)-wide outbreak related to frozen berries. However, as the sequenced HAV genome regions were only partly comparable between countries, results were not always conclusive.AimThe objective was to gather information on HAV surveillance and sequencing in EU/European Economic Area (EEA) countries to find ways to harmonise their procedures, for improvement of cross-border outbreak responses.MethodsIn 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on HAV surveillance practices in EU/EEA countries. The survey enquired whether a referral system for confirming primary diagnostics of hepatitis A existed as well as a central collection/storage of hepatitis A cases' samples for typing. Questions on HAV sequencing procedures were also asked. Based on the results, an expert consultation proposed harmonised procedures for cross-border outbreak response, in particular regarding sequencing. In 2016, a follow-up survey assessed uptake of suggested methods.ResultsOf 31 EU/EEA countries, 23 (2014) and 27 (2016) participated. Numbers of countries with central collection and storage of HAV positive samples and of those performing sequencing increased from 12 to 15 and 12 to 14 respectively in 2016, with all countries typing an overlapping fragment of 218 nt. However, variation existed in the sequenced genomic regions and their lengths.ConclusionsWhile HAV sequences in EU/EEA countries are comparable for surveillance, collaboration in sharing and comparing these can be further strengthened.

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.

Assessment of the Roche Linear Array HPV Genotyping Test within the VALGENT framework.

BACKGROUND: Cervical cancer screening programs are switching from cytology-based screening to high-risk (hr) HPV testing. Only clinically validated tests should be used in clinical practice. OBJECTIVES: To assess the clinical performance of the Roche Linear Array HPV genotyping test (Linear Array) within the VALGENT-3 framework. STUDY DESIGN: The VALGENT framework is designed for comprehensive comparison and clinical validation of HPV tests that have limited to extended genotyping capacity. The Linear Array enables type-specific detection of 37 HPV types. For the purpose of this study, Linear Array results were designated as positive only if one of the 13 hrHPV types also included in the Hybrid Capture 2 (HC2) was detected. The VALGENT-3 framework comprised 1600 samples obtained from Slovenian women (1300 sequential cases from routine cervical cancer screening enriched with 300 cytological abnormal samples). Sensitivity for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) (n=127) and specificity for

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Cardiovascular risk assessment in HIV-infected male patients: a comparison of Framingham, SCORE, PROCAM and DAD risk equations.

INTRODUCTION: Traditional cardiovascular (CVD) risk assessment algorithms such as the Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation (SCORE) and Prospective Cardiovascular Munster (PROCAM) were developed for general populations, their usefulness in HIV-infected population has not been confirmed. DAD algorithm was developed specifically for HIV-infected patients. The aim of our study was to evaluate the performance of risk assessment algorithms in HIV-infected population. METHODS: A prospective cross-sectional national study that included 83 HIV-infected male patients from Slovenia below the age of 55 was performed. CVD risk was assessed using four algorithms, the presence of subclinical atherosclerosis was determined by measuring carotid intima-media thickness (CIMT); patients were followed up for 5 years. RESULTS: High proportion of patients with low CVD risk according to FRS (61.9%) and PROCAM (81.0%) and only 7.1% according to SCORE had evidence of subclinical atherosclerosis. Only 7.1% of patients with low CVD risk according to DAD algorithm had evidence of subclinical atherosclerosis. CONCLUSION: Our study has shown that SCORE and DAD algorithm were superior to FRS and PROCAM. In younger HIV-infected patients, even with moderate CVD risk, CIMT assessment should be employed in a complete clinical evaluation as a more aggressive prevention and treatment approach is warranted.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Cervical cancer burden and prevention activities in Europe.

Cervical cancer is an important public health care problem in Europe. The overall incidence rate of cervical cancer in Europe is 10.6 per 100,000. However, within Europe, the incidence rates significantly differ, being lower in Western Europe where prevention programs are better developed. Significantly higher are the incidence and mortality rates in Central and Eastern Europe, being in close correlation to the intensity of organized screening. Human papillomavirus (HPV) vaccines are being delivered to the low-incidence populations that already have extensive screening programs, whereas the high-incidence countries have not implemented the vaccination programs yet. The resolution of the problem of cervical cancer control in Europe will be a matter of the implementation of public health care programs across the whole continent.

Twenty-four mini-pool HCV RNA screening in a routine clinical virology laboratory setting: a six-year prospective study.

The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy was re-evaluated after a six-year continuous routine use in a clinical virology laboratory, at which more than half of newly diagnosed hepatitis C patients are intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV negative serum samples and tested using an automated commercial PCR assay with a lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV RNA positive patients, responsible physicians provided follow-up samples. Thirty-eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28 intravenous drug users) were detected. Follow-up samples were available for 27/30 patients. Twenty, six and one patient seroconverted in the second, third and fourth available samples, respectively. The interval between the first HCV RNA positive and the first available anti-HCV positive sample was 17-517 days. The costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227 Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost effective strategy, not only in blood-transfusion settings but also in a routine clinical virology laboratory, at which a significant proportion of the tested population belongs to a high-risk population.

Twenty-four mini-pool HCV RNA screening outside a blood transfusion setting: results of a 2-year prospective study.

The usefulness of 24 mini-pool hepatitis C virus (HCV) RNA screening was evaluated in a 2-year prospective study carried out on a total of 6432 consecutive anti-HCV negative specimens in a routine diagnostic laboratory setting. A total of 268 mini-pools were tested using an automated commercial PCR assay for qualitative detection of HCV RNA, with a lower limit of detection of 50 IU/ml. Eighteen (0.28%) anti-HCV negative/HCV RNA positive serum samples obtained from 12 patients (all intravenous drug users), were detected. Ten patients responded to an invitation for follow-up testing. Five, three and one patient seroconverted in the first, second and third follow-up sample, respectively. One patient had not seroconverted by the end of the study period. The interval between the first HCV RNA positive sample and the first anti-HCV positive samples was 24-192 days. The costs of detecting a single anti-HCV negative/HCV RNA positive sample and a single anti-HCV negative/HCV RNA positive patient using the 24 mini-pool HCV RNA screening strategy were estimated to be around euro 643 and 965, respectively. It was shown that screening for HCV infection using the 24 mini-pool HCV RNA screening strategy can also be both useful and cost effective outside a blood transfusion setting.