A type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin, membrane-bound and soluble BDCA-2.

Plasmacytoid dendritic cells (pDCs) produce type I interferons (IFNs) after sensing viral/bacterial RNA or DNA by toll-like receptor (TLR) 7 or TLR9, respectively. However, aberrant pDCs activation can cause adverse effects on the host and contributes to the pathogenesis of type I IFN-related autoimmune diseases. Here, we show that heparin interacts with the human pDCs-specific blood dendritic cell antigen 2 (BDCA-2) but not with related lectins such as DCIR or dectin-2. Importantly, BDCA-2-heparin interaction depends on heparin sulfation and receptor glycosylation and results in inhibition of TLR9-driven type I IFN production in primary human pDCs and the pDC-like cell line CAL-1. This inhibition is mediated by unfractionated and low-molecular-weight heparin, as well as endogenous heparin from plasma, suggesting that the local blood environment controls the production of IFN-α in pDCs. Additionally, we identified an activation-dependent soluble form of BDCA-2 (solBDCA-2) in human plasma that functions as heparin antagonist and thereby increases TLR9-driven IFN-α production in pDCs. Of importance, solBDCA-2 levels in the serum were increased in patients with scrub typhus (an acute infectious disease caused by Orientia tsutsugamushi) compared to healthy control subjects and correlated with anti-dsDNA antibodies titers. In contrast, solBDCA-2 levels in plasma from patients with bullous pemphigoid or psoriasis were reduced. In summary, this work identifies a regulatory network consisting of heparin, membrane-bound and solBDCA-2 modulating TLR9-driven IFN-α production in pDCs. This insight into pDCs function and regulation may have implications for the treatment of pDCs-related autoimmune diseases.

Antimony Isotope Fractionation during Kinetic Sb(III) Oxidation by Antimony-Oxidizing Bacteria Pseudomonas sp. J1.

Antimony (Sb) isotopic fractionation is frequently used as a proxy for biogeochemical processes in nature. However, to date, little is known about Sb isotope fractionation in biologically driven reactions. In this study, Pseudomonas sp. J1 was selected for Sb isotope fractionation experiments with varying initial Sb concentration gradients (50-200 µM) at pH 7.2 and 30 °C. Compared to the initial Sb(III) reservoir (δ123Sb = 0.03 ± 0.01 ∼ 0.06 ± 0.01‰), lighter isotopes were preferentially oxidized to Sb(V). Relatively constant isotope enrichment factors (ε) of -0.62 ± 0.06 and -0.58 ± 0.02‰ were observed for the initial Sb concentrations ranging between 50 and 200 µM during the first 22 days. Therefore, the Sb concentration has a limited influence on Sb isotope fractionation during Sb(III) oxidation that can be described by a kinetically dominated Rayleigh fractionation model. Due to the decrease in the Sb-oxidation rate by Pseudomonas sp. J1, observed for the initial Sb concentration of 200 µM, Sb isotope fractionation shifted toward isotopic equilibrium after 22 days, with slightly heavy Sb(V) after 68 days. These findings provide the prospect of using Sb isotopes as an environmental tracer in the Sb biogeochemical cycle.

Human papillomavirus prevalence in pregnant women living with human immunodeficiency virus infection: a scoping review of the literature.

OBJECTIVES: Studies already pointed out the increased risk of human papillomavirus (HPV) positivity and the implied risk of cervical dysplasia and even cervical carcinoma in pregnant women with human immunodeficiency virus (HIV) infection. Nevertheless, due to less data there is still no standardised and expanded screening for this high-risk group. CONTENT: Two online databases (PubMed, EMBASE) were used to identify eligible studies. Results are shown in percentages. Wherever useful the arithmetic mean was calculated. SUMMARY: Seven studies were included. Pregnant WLWH showed HPV prevalence between 34 and 98.4 %. Different sensitivity and specificity among PCR methods for HPV detection could be a reason for the large range concerning HPV prevalence. Risk factors like Age, Smoking, Sexuality, HIV status and education level should always be taken into account. Association between HPV prevalence and level of CD4 cells or HIV virus load was seen. In which way use of Antiretroviral Therapy (ART) could decries the risk for HPV infections is still discussed. When cytology was performed only few high-grade squamous intraepithelial lesion (HSIL) were found. OUTLOOK: Standardisation and expansion of preventive screening for cervical dysplasia and carcinoma for pregnant WLWH is necessary. Then better comparability of the data will also be achieved.

Integration and viral oncogene expression of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma and gastric cancer.

Persistent high-risk human papillomavirus (HR-HPV) infections cause cervical cancer and a fraction of head and neck cancer. To investigate whether HR-HPV infection might be also involved in the development of gastric cancer (GC), we developed a platform utilizing a rolling circle amplification (RCA)-based nested L1 polymerase chain reaction with Sanger sequencing to genotype the HPV DNA in cancer tissues of 361 GC and 89 oropharyngeal squamous cell carcinomas (OPSCC). HPV transcriptional activity was determined by E6/E7 mRNA expression and a 3' rapid amplification of cDNA ends was performed to identify HPV integration and expression of virus-host fusion transcripts. Ten of 361 GC, 2 of 89 OPSCC, and 1 of 22 normal adjacent tissues were HPV L1 DNA-positive. Five of the 10 HPV-positive GC were genotyped as HPV16 by sequencing and 1 of 2 GC with RCA/nested HPV16 E6/E7 DNA detection exhibited HPV16 E6/E7 mRNA. Two OPSCC displayed HPV16 L1 DNA and E6/E7 mRNA, of which 1 OPSCC tissue showed virus-host RNA fusion transcripts from an intron region of KIAA0825 gene. Together, our data reveal viral oncogene expression and/or integration in GC and OPSCC and a possible etiology role of HPV infections in gastric carcinogenesis.

Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL-6-mediated protection associated with cecal microbiota changes.

BACKGROUND: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown. METHODS: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6-/- , Il10-/- , and Il17-/- mice exposed to ovalbumin-induced allergic airway inflammation. Those investigations were expanded by microbiome analyses. To assess for AL-associated changes in gene expression, the picture arising from animal data was supplemented by in vitro experiments of macrophage and T-cell responses, yielding expression and epigenetic data. RESULTS: The asthma preventive effect of AL was confirmed in the lung. Repeated intranasal AL administration triggered a proinflammatory immune response particularly characterized by elevated levels of IL-6, and consequently, IL-6 induced IL-10 production in CD4+ T-cells. Both IL-6 and IL-10, but not IL-17, were required for asthma protection. AL had a profound impact on the gene regulatory landscape of CD4+ T-cells which could be largely recapitulated by recombinant IL-6. AL administration also induced marked changes in the gastrointestinal microbiome but not in the lung microbiome. By comparing the effects on the microbiota according to mouse genotype and AL-treatment status, we have identified microbial taxa that were associated with either disease protection or activity. CONCLUSION: These experiments provide a novel mechanism of Acinetobacter lwoffii-induced asthma protection operating through IL-6-mediated epigenetic activation of IL-10 production and with associated effects on the intestinal microbiome.

Upscaling cervical cancer screening and treatment for women living with HIV at a rural referral hospital in Tanzania: protocol of a before-and-after study exploring HPV testing and novel diagnostics.

BACKGROUND: Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. METHODS: This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. DISCUSSION: The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway.

RNA has been proposed as an important scaffolding factor in the nucleus, aiding protein complex assembly in the dense intracellular milieu. Architectural contributions of RNA to cytosolic signaling pathways, however, remain largely unknown. Here, we devised a multidimensional gradient approach, which systematically locates RNA components within cellular protein networks. Among a subset of noncoding RNAs (ncRNAs) cosedimenting with the ubiquitin-proteasome system, our approach unveiled ncRNA MaIL1 as a critical structural component of the Toll-like receptor 4 (TLR4) immune signal transduction pathway. RNA affinity antisense purification-mass spectrometry (RAP-MS) revealed MaIL1 binding to optineurin (OPTN), a ubiquitin-adapter platforming TBK1 kinase. MaIL1 binding stabilized OPTN, and consequently, loss of MaIL1 blunted OPTN aggregation, TBK1-dependent IRF3 phosphorylation, and type I interferon (IFN) gene transcription downstream of TLR4. MaIL1 expression was elevated in patients with active pulmonary infection and was highly correlated with IFN levels in bronchoalveolar lavage fluid. Our study uncovers MaIL1 as an integral RNA component of the TLR4-TRIF pathway and predicts further RNAs to be required for assembly and progression of cytosolic signaling networks in mammalian cells.

Assessment of high-risk human papillomavirus infections and associated cervical dysplasia in HIV-positive pregnant women in Germany: a prospective cross-sectional two-centre study.

PURPOSE: Invasive cervical cancer (ICC) is associated in nearly 100% with persistent high-risk Human Papillomavirus (HR-HPV) infection. ICC is still one of the leading causes for cancer mortality in women worldwide. The immunosuppressive influence of Human Immunodeficiency Virus (HIV) and the immunocompromised period of pregnancy due to tolerance induction against the hemiallogeneic fetus, are generally risk factors for acquisition and persistence of HR-HPV infections and their progression to precancerous lesions and HPV-associated carcinoma. METHODS: Overall, 81 pregnant women living with HIV (WLWH) were included. A medical history questionnaire was used to record clinical and HIV data. Participants received cervicovaginal cytological smear, colposcopy and HPV testing. HPV test was performed using BSGP5+/6+ PCR with Luminex read-out. The HR-HPV genotypes 16, 18, 31, 33, 45, 52, 58 were additionally grouped together as high-high-risk HPV (HHR-HPV) for the purpose of risk-adapted analysis. RESULTS: HR-HPV prevalence was 45.7%. Multiple HPV infections were detected in 27.2% of participants, of whom all had at least one HR-HPV genotype included. HR-HPV16 and HR-HPV52 were the most prevalent genotypes and found when high squamous intraepithelial lesion (HSIL) was detected by cytology. HIV viral load of ≥ 50 copies/ml was associated with higher prevalence of HR-HPV infections. Whereas, CD4 T cells < 350/µl showed association with occurrence of multiple HPV infections. Time since HIV diagnosis seemed to impact HPV prevalence. CONCLUSION: Pregnant WLWH require particularly attentive and extended HPV-, colposcopical- and cytological screening, whereby clinical and HIV-related risk factors should be taken into account.

The Significance of Cancer Stem Cells and Epithelial-Mesenchymal Transition in Metastasis and Anti-Cancer Therapy.

Cancer stem cells (CSCs) have been identified and characterized in both hematopoietic and solid tumors. Their existence was first predicted by Virchow and Cohnheim in the 1870s. Later, many studies showed that CSCs can be identified and isolated by their expression of specific cell markers. The significance of CSCs with respect to tumor biology and anti-cancer treatment lies in their ability to maintain quiescence with very slow proliferation, indefinite self-renewal, differentiation, and trans-differentiation such as epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET). The ability for detachment, migration, extra- and intravasation, invasion and thereby of completing all necessary steps of the metastatic cascade highlights their significance for metastasis. CSCs comprise the cancer cell populations responsible for tumor growth, resistance to therapies and cancer metastasis. In this review, the history of the CSC theory, their identification and characterization and their biology are described. The contribution of the CSC ability to undergo EMT for cancer metastasis is discussed. Recently, novel strategies for drug development have focused on the elimination of the CSCs specifically. The unique functional and molecular properties of CSCs are discussed as possible therapeutic vulnerabilities for the development of novel anti-metastasis treatments. Prospectively, this may provide precise personalized anti-cancer treatments with improved therapeutic efficiency with fewer side effects and leading to better prognosis.

Genotype-specific high-risk human papillomavirus infections and risk factors for cervical dysplasia in women with human immunodeficiency virus in Germany: results from a single-center cross-sectional study.

OBJECTIVE: Women living with HIV have an increased risk of human papillomavirus (HPV) infection and cervical cancer. Little is known about genotype-specific HPV prevalence, the impact of antiretroviral therapy, immunological status, and additional risk factors in women living with HIV in Germany. The goal of this study was to characterize the risk profile for cervical dysplasia in these women. METHODS: Patients with HIV infection presenting at Charité-Universitätsmedizin Berlin from October 2017 to September 2020 were included and underwent gynecological examination, colposcopy, cervical cytology and HPV genotype testing. HPV genotypes were stratified by carcinogenicity. Atypical squamous cells of undetermined significance or higher were considered abnormal cytology. Data were analyzed by SPSS software (version 26, 2019). A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: A total of 84 women were evaluated. The majority (95.2%) received antiretroviral therapy. Median CD4 cell count was 564 cells/µl (range 20-1969). 95.2% were previously screened for cervical cancer. High-risk HPV prevalence was 44%. High-high-risk HPV subtypes (16, 18, 31, 33, 45, 52, 58) were significantly associated with abnormal cytology (p<0.001). HPV16 was the most common genotype (23%), was significantly associated with abnormal cytology (p=0.002) and was the main risk factor for abnormal cytology (OR 8.55, 95% CI 2.15 to 34.13, p=0.002), followed by age <35 years (OR 4.96, 95% CI 1.23 to 19.61, p=0.033) and cigarette smoking (OR 3.944, 95% CI 0.98 to 15.88, p=0.053). CONCLUSIONS: Antiretroviral therapy and adherence to cervical cancer screening was high. High-high-risk HPV, especially HPV16, coincided with high incidence of cytological abnormalities. Women living with HIV in Germany have adequate immune status and are often pre-screened for cervical cancer, and therefore have a different risk profile for cervical dysplasia than in low-income or medium-income countries. Adapted screening programs should be defined.

A ribosomal RNA fragment with 2',3'-cyclic phosphate and GTP-binding activity acts as RIG-I ligand.

The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded RNA structures bearing 5'-tri- or diphosphates are commonly referred to as activating RIG-I ligands. However, endogenous RNA fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested RNA fragments bear a 5'-hydroxyl group and a 2',3'-cyclic phosphate. How endogenous RNA fragments activate RIG-I despite the lack of 5'-phosphorylation has not been elucidated. Here we describe an endogenous RIG-I ligand (eRL) that is derived from the internal transcribed spacer 2 region (ITS2) of the 45S ribosomal RNA after partial RNase A digestion in vitro, RNase A protein transfection or RNase L activation. The immunostimulatory property of the eRL is dependent on 2',3'-cyclic phosphate and its sequence is characterized by a G-quadruplex containing sequence motif mediating guanosine-5'-triphosphate (GTP) binding. In summary, RNase generated self-RNA fragments with 2',3'-cyclic phosphate function as nucleotide-5'-triphosphate binding aptamers activating RIG-I.

Population-based human papillomavirus infection and genotype distribution among women in rural areas of South Central Ethiopia.

In Ethiopia, cervical cancer is the second leading cause of morbidity and mortality from all cancers in women. Persistent infection with human papillomaviruses (HPV) plays a key role in the development of cervical intraepithelial neoplasia and invasive cervical cancer. To establish baseline data on the population-based prevalence of HPV infection and genotype distribution, we investigated cervical HPV epidemiology among rural women. This population-based study was conducted among rural women aged 30-49 years in Butajira, south-central Ethiopia. A total of 893 samples were tested from 1020 screened women. A self-sampling device (Evalyn Brush, Rovers, Oss, The Netherlands) was used and HPV presence and genotype was determined using multiplexed genotyping (MPG) by BSGP5+/6+ PCR with Luminex read out. The HPV positivity rate was 23.2% (95% CI: 23.54-22.86%) and 20.5% (95% CI = 20.79-20.21) and 10.3% (95% CI = 10.52-10.08) women were high-risk (hr- and low-risk (lr-) HPV positive, respectively. Fifty five (7.2%) of the women showed multiple hr-HPV infections. Age-specific hr-HPV infection peaked in the age-group 30- to 34 years old (58.6%) and decreased in 35-39, 40-44 and 45-49 years to 20.4%, 4.5% and 3.8% respectively. The top five prevalent hr-HPV genotypes were HPV16 (57.1%), 35 (20.3%), 52 (15.8%), 31 (14.1%), and 45 (9.6%) in the Butajira district. As a first population-based study in the country, our results can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs in Ethiopia.

Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors.

The genome of vertebrates contains endogenous retroviruses (ERVs) that are largely nonfunctional relicts of ancestral germline infection by exogenous retroviruses. However, in some mouse strains ERVs are actively involved in disease. Here we report that nucleic acid-recognizing Toll-like receptors 3, 7, and 9 (TLR 3, TLR7, and TLR9) are essential for the control of ERVs. Loss of TLR7 function caused spontaneous retroviral viremia that coincided with the absence of ERV-specific antibodies. Importantly, additional TLR3 and TLR9 deficiency led to acute T cell lymphoblastic leukemia, underscoring a prominent role for TLR3 and TLR9 in surveillance of ERV-induced tumors. Experimental ERV infection induced a TLR3-, TLR7-, and TLR9-dependent group of "acute-phase" genes previously described in HIV and SIV infections. Our study suggests that in addition to their role in innate immunity against exogenous pathogens, nucleic acid-recognizing TLRs contribute to the immune control of activated ERVs and ERV-induced tumors.

Prevalence of human papillomavirus detection in ovarian cancer: a meta-analysis.

We conducted a meta-analysis of published data to update and estimate the prevalence of HPV in ovarian cancer. A comprehensive literature search was performed according to the PRISMA guidelines. Eligible articles published from 1989 until 2020 by searching Web of Sciences, Pubmed, Embase, and the Cochrane Library Central databases were gathered. A pooled estimation of HPV prevalence with a 95% confidence interval (CI) was calculated based on a random effect model. Quantitative assessment of heterogeneity was explored using Cochrane test and I2. Additionally, publication bias, sensitivity, meta-regression, and subgroup analyses were also performed. Twenty-nine studies involving 2280 patients with ovarian cancer were included. The statistical heterogeneity was high (I2 = 88%, P<0.0001). The pooled prevalence of HPV in ovarian cancer cases was 15.9% (95% CI, 11-22). In subgroup analyses, the highest prevalence of HPV was reported by studies from Asia (30.9%; 95% CI, 20-44) and Eastern Europe (29.3%; 95% CI, 4.4-78). Furthermore, the most frequently detected HPV genotype was HPV16 (54%; 95% CI, 27.9-55), followed by HPV18 (23.2%; 95% CI, 18.8-28.2). Our meta-analysis suggests a great difference in the prevalence of HPV detected in ovarian cancer by different studies, which is not seen in strongly HPV-associated cancers such as cervical cancer. However, the prevalence varied markedly by geographic region. Considering the substantial heterogeneity found, more studies with control groups and precise assays measuring HPV mRNA expression are needed to further evaluate the link and causative aetiology between HPV and ovarian cancer.

ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function.

RNA editing by adenosine deaminases acting on dsRNA (ADAR) has become of increasing medical relevance, particularly because aberrant ADAR1 activity has been associated with autoimmunity and malignancies. However, the role of ADAR1 in dendritic cells (DC), representing critical professional APCs, is unknown. We have established conditional murine CD11c Cre-mediated ADAR1 gene ablation, which did not induce general apoptosis in CD11c+ cells but instead manifests in cell type-specific effects in DC subpopulations. Bone marrow-derived DC subset analysis revealed an incapacity to differentiate CD103 DC+ in both bulk bone marrow and purified pre-DC lineage progenitor assays. ADAR1 deficiency further resulted in a preferential systemic loss of CD8+/CD103+ DCs, revealing critical dependency on ADAR1, whereas other DC subpopulations were moderately affected or unaffected. Additionally, alveolar macrophages were depleted and dysfunctional, resembling pulmonary alveolar proteinosis. These results reveal an unrecognized role of ADAR1 in DC subset homeostasis and unveils the cell type-specific effects of RNA editing.

The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer.

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.

German evidence and consensus-based (S3) guideline: Vaccination recommendations for the prevention of HPV-associated lesions.

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

Clinical performance of the HPV DNA Array genotyping assay in detection of CIN2+ lesions with BS GP5+/6+ MPG Luminex tested cervical samples.

Human papillomavirus (HPV) detection is used for screening of cervical cancer and genotype-specific persistence has shown to be mandatory for dysplasia development. Aim of this study was to evaluate the clinical performance of HPV DNA Array for cervical intraepithelial neoplasia 2+ (CIN2+) lesion detection. HPV DNA Array is a polymerase chain reaction-based assay that targets E1 sequences of 29 HPV types (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, 85, and 97). The clinical evaluation was performed against the reference assay, BS-GP5+/6+ multiplex genotyping (MPG)-Luminex, with 600 cervical smear samples of a referral population. HPV DNA Array detected CIN2+ lesions with a sensitivity of 90.2%, identical to that of MPG-Luminex. Detection of CIN3+ lesions was with a sensitivity of 90.3%, as compared with 88.7% of MPG-Luminex. It demonstrated very good agreement for HPV detection, irrespective of type, of 91.5% (κ = 0.832). HPV DNA Array is a simple and robust assay, with a short protocol of 4 hours hands-on time and automated readout by ELISpot AiDot software. It permits testing of up to 96 samples in one run and may be considered for use in organized screening programs and low resource settings.

Cervical cancer screening in rural Ethiopia: a cross- sectional knowledge, attitude and practice study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Sub- Saharan Africa has a high incidence, prevalence and mortality due to shortage and underutilization of screening facilities. This study aims to assess knowledge and attitude towards cervical cancer and its prevention, as well as practice of cervical cancer screening. METHODS: This cross-sectional community- based study was conducted in Butajira, Ethiopia in February 2018. Systematic cluster randomized sampling was used to select households from which women in the targeted age group of 30-49 years were invited to participate. Data was collected using a quantitative door to door approach. The questionnaire included socio-demographic data, obstetric history, general knowledge, risk factors, attitude and practice. Logistic regression was used to assess factors associated with knowledge, attitude and practice after dichotomizing the scores using the median as cut off point. RESULTS: Three hundred forty-two out of 354 women completed the interviewer administered questionnaire making the response rate 96.3%. 125 women (36%) were aware of cervical cancer and 14 (4.7%) knew symptoms. None of the women named HPV as a risk factor. 61% thought it was a deadly disease, 13.5% felt at risk of developing cervical cancer and 60.7% said cervical cancer is treatable. Eight women (2.3%) had previously been screened. 48.1% had a source of information concerning cervical cancer, of which 66.5% named nurses. Better knowledge was associated with 1-8 years of education (OR = 2.4; CI: 2.4-1.3), having a source of information (OR = 9.1, CI:4.0-20.6), use of contraceptives (OR = 2.3, CI: 1.3-4.0) and a higher income (OR = 1.009, CI: 1.00-1.01). Naming nurses (OR:5.0, CI:2.4-10.3), another source of information (OR = 3.3, CI:1.2-9.0), use of contraceptives (OR = 2.2, CI:1.2-3.8) and living in an urban area (OR = 3.3, CI:1.2-9.0) were associated with a positive attitude. Naming nurses (OR = 21,0, CI:10.4-42.3) and another source of information (OR = 5.8, CI:2.4-13.5) were associated with participating in cervical cancer screening. CONCLUSION: Most women were unaware of cervical cancer, HPV-infection as a risk factor and did not feel susceptible to cervical cancer. As Health workers were the most commonly mentioned source of information, focus should be put on their further education.

Reactive oxygen species in cancer stem cells of head and neck squamous cancer.

One of the greatest challenges in systemic treatment of head and neck squamous cell carcinoma (HNSCC) is a small tumor cell population, namely, cancer stem-like cells (CSC). CSC can regenerate and maintain a heterogenic tumor by their self-renewal capacity. Their potential ability to be more resistant to and survival after chemo- and radiation therapy was also identified. Further studies have shown that reactive oxygen species (ROS) contribute to this CSC-associated resistance. In this review, we focus on the current knowledge of HNSCC-CSC, with regard to ROS as a possible and novel therapeutic approach in targeting CSC.