Human papillomavirus in tonsillectomy specimen from China and Pakistan — Prevalence and genotype distribution

Background

The expected corresponding increase in tonsillar human papillomavirus (HPV) infection associated with increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) substantiate the evaluation of normal tonsillar tissue in different population. The epidemiology of HPV in tonsillar tissue varies geographically. This study evaluated samples from two countries to determine the prevalence in respective samples.

Molecular epidemiology of human papillomavirus genotype in women with high‐grade squamous intraepithelial lesion and cervical cancer: Will a quadrivalent vaccine be necessary in Thailand?

This study was designed to investigate the distribution of human papillomavirus (HPV) genotypes among a group of patients with high-grade squamous intraepithelial lesion (HSIL) or worse cytology. Consequently, the genotype-specific HPV infection in a group of HSIL and invasive cervical cancer (ICC) samples was described. Specimens were collected prospectively from 132 women referred for colposcopic examination. All the women underwent Papanicolaou (Pap) smears and colposcopies and some also underwent cervical excision procedure biopsy. The HPV genotype was determined using the INNO-LiPA assay. Among the 132 genotyped samples, 90.91% (120/132) were diagnosed HSIL, whereas 9.09% (12/132) were ICC. From the overall prevalence of HPV in the patients, 77.27% (102/132) and 22.72% (30/132) of cases had single and multiple genotype infections, respectively. The most common cases with statistical significance were high-risk HPV (HR-HPV) infections in 128 samples (96.97%), whereas, four individuals (3.03%) barely were low-risk HPV (LR-HPV) infected, P < 0.0001, χ(2). The most prevalent genotypes were frequently HPV-16 (65/167; 38.92%, followed by HPV-58 (25/167; 14.97%), HPV-18 (18/167; 10.78%), HPV-33 (13/167; 7.19%), and HPV-68 (11/167; 6.59%). In addition, HPV-11 (2/132; 1.51%) and HPV-6 (1/132; 0.76%) also were observed in this study, which confirmed the high distribution of HR-HPV among women with HSIL and ICC. HPV-58; a unique high-risk HPV, is prevalent in a group of HSIL and ICC cases. These data also contribute evidence that HPV-16, -18, -58, -33, and -68 genotypes are high-risk and high distribution among women with HSIL and ICC. Therefore, HPV-58, HPV-33, and HPV-68 should be considered for development of the next vaccine generation in Thailand.     

Cervical human papillomavirus among 19 753 women attending gynecological department of a major comprehensive hospital in north Anhui China 2013-2016: Implication for cervical cancer screening and prevention

Our study aimed to assess the prevalent, incident, and persistent infection, and clearance of HPV among 19 753 individual women attending the gynecological department at a major comprehensive hospital. HPV 16, 52, and 58 ranked top three types with the highest prevalence and incidence. The prevalence of high-risk (HR) HPV peaked among women aged 15 to 19 years, then sharply decreased with age, stabilized among women aged 25 to 44 years, and then surged again among women aged 45 years and older. HR HPV infection were more likely to be prevalent (15.9% vs 1.3%, P < 0.001), incident (17.3 vs 2.0 per 1000 person-months, P < 0.001), and persistent (33.0% vs 24.2%, P = 0.033), and less likely to clear (88 vs 115 per 1000 person-months, P = 0.040) compared to low-risk HPV types. The majority of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education and counseling about HPV infection and its implications for women detected with HPV at clinical settings are warranted.     

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18–45 years enrolled in a clinical trial

ObjectivesData from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies.MethodsFrom November 2012 to April 2013, a total of 7372 healthy women aged 18–45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay.ResultsThe overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0–15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18–26 years) and middle-aged women (27–45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18).DiscussionThis study revealed that the majority of Chinese women aged 18–26 years and 27–45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.     

Aberrant staining patterns of E-cadherin and β-catenin: a potential diagnostic value for distinguishing vulvar intraepithelial neoplasia from non-neoplastic vulvar lesions

Histologically, vulvar intraepithelial neoplasm (VIN) is a proliferative disorder of the female vulva. No single clinical characteristic or pathognomonic feature facilitates the diagnosis of VIN, and the agreement between different pathologists on the diagnoses varies significantly. In this study, we evaluate the immunohistochemical expression patterns of E-cadherin and β-catenin in 22 patients with VIN and 10 patients with non-neoplastic vulvar lesions. our results showed that membranous staining for E-cadherin and β-catenin was observed in squamous epithelial cells of all control non-neoplastic vulvar samples. Abnormal E-cadherin (17/19, 89.5%) and β-catenin (15/19, 78.9%) staining occurred more frequently in usual-type VIN than in non-neoplastic vulvar lesions (P=0.000 and P=0.000, respectively). However, in differentiated VIN, only 1 patient showed abnormal E-cadherin and β-catenin immunohistochemical expressions, which did not differ significantly. The abnormal expression of E-cadherin and β-catenin proteins might be useful in distinguishing VIN from non-neoplastic vulvar squamous epithelium lesions in problematic cases.     

Status analysis and evaluation of the blood scrap rate from 2015–2017 for a blood center in China

ObjectivesThe objective of this study was to ascertain the current conditions and development in the past three years of clinical transfusion practice in Nanjing, Jiangsu province, China.Materials and methodsBlood quality control practices and the blood production scrap rate from 2015–2017 were monitored and measured using different quality statistics and management tools.ResultsThe causes of unqualified and scrapped blood during blood collection and supply were analyzed and evaluated. The analysis of the key indices for blood component quality control showed that the qualified rate of FVIII activity (from fresh frozen plasma) was 54.55%, which failed to meet the threshold of 75%. Retrospective analysis of conventional blood scrapping factors showed that laboratory scraps accounted for the majority. The composition ratio of TTI screening results included ALT (31.91%), HBV (21.92%), TP (12.15%), NAT (10.78%), HCV (8.45%), and HIV (7.43%). Retrospective analysis of unconventional blood scrapping factors showed that the total unconventional blood depletion rate was 0.565%. Insufficient or small quantities of collected blood was the most important factor related to unconventional scrapping. The blood donor and blood hospital service satisfaction rates were over 95% and 90%, respectively, which achieved the quality target.ConclusionsNonconforming product control was proposed and determined as the urgent theme of the first QCC. It is necessary for blood stations to effectively control blood scrapping, which can reduce the cost of blood collection, protect the blood donation of unpaid blood donors, increase the rate of repeated blood donation, and improve blood safety.     

The characteristics of metallo-β-lactamase-producing gram-negative bacilli isolated from sputum and urine: a single center experience in Korea

Metallo-β-lactamase (MBL) production usually results in high-level resistance to most β-lactams, and a rapid spread of MBL producing major gram-negative pathogens is a matter of particular concern worldwide. However, clinical data are scarce and most studies compared MBL producer (MP) with MBL non-producer (MNP) strains which included carbapenem susceptible isolates. Therefore, we collected clinical data of patients in whom imipenem-nonsusceptible Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) were isolated from sputum or urine, and investigated MBL production and the risk factors related with MBL acquisition. The antimicrobial susceptibility patterns were also compared between MPs and imipenem-nonsusceptible MNPs (INMNP). Among the 176 imipenem-nonsusceptible isolates, 12 MPs (6.8%) were identified. There was no identifiable risk factor that contributed to the acquisition of MPs when compared to INMNPs, and case-fatalities were not different between the two groups. The percentage of susceptible isolates was higher among MPs for piperacilin/tazobactam and fluoroquinolones while that of ceftazidime was higher in INMNPs (p < 0.05). As regards to aztreonam, which has been known to be a uniquely stable β-lactam against MBLs, susceptibility was preserved in only two isolates (16.7%) among MPs, and was not higher than that of INMNPs (23.2%). In conclusion, the contribution of MBLs to imipenem non-susceptibility in PA/ABs isolated from sputum and urine was relatively limited, and there was no significant risk factor associated with acquisition of MPs compared with INMNPs. However, limited susceptibility to aztreonam implies that MPs may hold additional resistance mechanisms, such as extended spectrum β-lactamases, AmpC β-lactamases, or other non-enzymatic mechanisms.     

Association between tumor necrosis factor-α gene polymorphisms and diffuse large B-cell lymphoma in Chinese Han population: evidence from two center case-control study and a meta-analysis

Objectives: The tumor necrosis factor-α (TNF-α) gene, which plays crucial roles in tumorigenesis, is reported to be an independent marker for cancer. This study aims to examine the association between the TNF-α G308A polymorphism and DLBCL risk based on the two center case-control studies and meta-analysis. Methods: In the current study, we performed a two centers case-control study to investigate the effect of the TNF-α G308A polymorphism on DLBCL risk in Chinese Han population. A meta-analysis including 10 published datasets along with current dataset, including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled, was next performed to further confirm the association after literature search was conducted and relevant studies were identified from PubMed, Embase, and Web of Science. Results: The TNF-α -308A allele was associated with a significantly increased DLBCL risk in the two independent patient case-control studies and additionally for pooled analysis from the two sets (P<0.05 for both). The result of meta-analysis further demonstrated that the A allele of -308A was significantly correlated with DLBCL risk under the allelic model (OR=1.35, 95% CI=1.27-1.44) without heterogeneity by fixed-effects model analysis (Q=17.30, P=0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis. Conclusion: This study suggested that -308A polymorphism may be associated with the susceptibility of DLBCL in a Chinese population. The further meta-analysis provides additional evidence supporting the above result that the risk allele of the -308A polymorphism may increase DLBCL risk.     

Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma?

BACKGROUND: The airway smooth muscle (ASM) cell, originally thought of as a passive structural cell, is now well recognized as an active participant in the pathologic events that occur during persistent asthma. Cell-surface molecules play an important role in the development of an immune response. A number of cell-surface molecules are expressed on ASM cells, and these might contribute to the inflammatory reaction. OBJECTIVE: The purpose of this study was to determine whether OX40 ligand (OX40L), a molecule known to be involved in T-cell activation, was present on the ASM cell surface. METHODS: We used real-time RT-PCR to detect mRNA expression and flow cytometry, ELISA, and immunoprecipitation to detect the presence of cell-surface protein on ASM cells isolated from asthmatic and nonasthmatic individuals. ELISAs and Western blotting were used to determine the functional outcomes of engagement of OX40L. RESULTS: OX40L was present on both asthmatic and nonasthmatic ASM cells. Engagement of OX40L with recombinant OX40:Fc resulted in a significantly greater increase in release of IL-6 from ASM cells of asthmatic patients than from ASM cells of nonasthmatic patients (P<.01). Ligation of OX40L resulted in a rapid translocation of protein kinase C beta2 to the cell membrane. Conclusion: Because the receptor for OX40L, OX40, is expressed on CD4+ T cells within 48 hours of stimulation through the T-cell receptor, elucidation of the cross-talk between OX40 and OX40L could be very important in understanding the interaction of cells present in the inflamed airways of an asthmatic patient.     

Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

Hand–foot–mouth disease due to enterovirus 71 (EV71) and coxsackievirus A16 (CA16) has recently caused large outbreaks in mainland China in 2008. We performed complete genome sequencing on two EV71 (SZ/HK08-5 and SZ/HK08-6) and two CA16 (SZ/HK08-3 and SZ/HK08-7) strains from patients in Shenzhen, China. Phylogenetic, similarity plot and bootscan analyses revealed recombination between EV71 genotypes B and C at the 2A–2B junction, and between EV71 genotype B and CA16 strain G-10 in the 3C region for EV71 strains. A similar phenomenon was also found upon further gene sequencing with other EV71 strains. Recombination between CA16 strain G-10 and EV71 genotype A at the 2A–2B junction was also observed for CA16 strains. The present “double-recombinant” EV71 strains circulating in China and other EV71 subgenotype “C4” strains represent an additional genotype, D. CA16 strains should also be classified into two genotypes. This represents the first evidence for a combination of intratypic and intertypic recombination in EV71 strains.     

Measles incidence rate and a phylogenetic study of contemporary genotype H1 measles strains in China: is an improved measles vaccine needed?

The incidence of measles in China has increased over the last decade. To evaluate the genetic variation of measles strains, 16 measles wild-type virus strains were isolated from 14 vaccinated cases and 2 nonvaccinated cases in Jilin Province during 2005–2006, and their nucleoprotein (N) and hemagglutinin (H) genes were amplified by RT-PCR. The amplified products were sequenced and compared with the Edmonston virus and the existing vaccine strains (Changchun-47 and Shanghai-191). The results showed that the variation rate between the vaccine and wild-type strains was 9.8–12.0% in the N gene and 5.9–6.9% in the H gene, respectively. In addition, cross-neutralization assays revealed that although sera obtained from infants following primary vaccination effectively neutralized vaccine strains, the capacity in neutralizing H1 wild-type measles virus isolates was decreased fourfold. Antigenic ratios testing revealed that the antigenic relatedness between wild-type measles viruses and existing vaccine strains was notably low. These data suggest that the increased incidence of measles in Jilin Province may be attributed to the antigenic drift between wild-type and vaccine strains. Our findings strengthen the recommendation of supplemental immunization with existing vaccines and also strongly suggest a need for developing new vaccines to better control measles virus outbreaks.     

Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes

High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes—individually or epistatically—were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies.     

Prevalence of SARS-CoV-2 IgG antibodies in a large prospective cohort study of elite football players in Germany (May–June 2020): implications for a testing protocol in asymptomatic individuals and estimation of the rate of undetected cases

ObjectivesElite professional football players and staff are a unique group that might give insight into the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Germany and thus can serve as a model for geographical distribution and an estimation of undetected infections.MethodsIn this prospective cohort study seroprevalence was determined twice in May and June 2020 in players and staff from the German Bundesliga. As screening assays, a commercial ELISA (Euroimmun) and a chemiluminescent immunoassay (CLIA) (Roche) were used, and an in-house neutralization assay (NT) was used as reference standard. Participants were tested twice weekly using PCR from nasopharyngeal and/or oropharyngeal swabs.ResultsSeroprevalence (NT used as confirmation) in 2164 samples from 1184 players and staff was rather similar in May (23/1157, 1.99%) and June (21/1007, 2.09%). All participants were PCR-negative during the study period. Significant regional differences in seroprevalence were not observed. When comparing seroprevalence with the cumulative incidence of infections derived from the German notification system (subgroup matching to cohort; men, age 20–69 years), IgG was found eight to ten times more frequently, pointing to a high rate of undetected infection. ELISA and CLIA correlated only moderately (κ 0.52).ConclusionsSeroprevalence with a high-quality diagnostic in Germany seemed to be around 2%. The number of undetected infections seems to be eight to ten times higher than in notification data. The quality of antibody assays is rather variable, thus results should ideally be confirmed at least by a second assay to prove IgG positivity.     

Correlations of TOP2A gene aberrations and expression of topoisomerase IIα protein and TOP2A mRNA expression in primary breast cancer: a retrospective study of 86 cases using fluorescence in situ hybridization and immunohistochemistry

Our aim in this study was to assess the status of TOP2A gene aberrations (no change/amplification or deletion) and its correlations with topoisomerase IIα (Topo IIα) protein and TOP2A mRNA expression, respectively. TOP2A amplification, Topo IIα protein expression and TOP2A mRNA expression were assessed using samples of 86 cases of breast cancer by fluorescence in fluorescence in situ hybridization, quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Twenty two (22.57%) had amplification/deletion of TOP2A gene. Twenty eight (32.56%) tumor samples were 17q polysomy or monosomy. Topo IIα protein was expressed in 57 cases (66.27%, 57/86): 22 cases (38.62%, 22/57) and 35 cases (61.40%, 35/57) had amplification/deletion and no change of TOP2A gene, respectively. These three groups showed significant differences by one-way analysis of variance (P < 0.001). The average Ct values of TOP2A mRNA expression in the tumors with deletion, amplification and no change of TOP2A gene were 27.00, 27.33 and 31.66, respectively. We demonstrated that the TOP2A gene was amplified or deleted in breast cancer, with a significant correlation with high expressions of Topo IIα protein and TOP2A mRNA expression. Ki-67 expression index (mean = 14.9) decreased significantly in cases wherein TOP2A gene had no change and Her2/neu protein expression was weakly positive (0-1+, P < 0.001).     

Testicular changes during infantile 'quiescence' in the marmoset and their gonadotrophin dependence: a model for investigating susceptibility of the prepubertal human testis to cancer therapy?

BACKGROUND: Inexplicably, boys treated with some therapies for cancer at age 2-10 years, a time of supposed 'testicular quiescence', are at risk of low sperm counts/infertility in adulthood. Our aims were to use the marmoset as a surrogate for man to establish testicular cell function/activity during 'quiescence' between the neonatal period and puberty, and to test if any cell activity could be suppressed by prior treatment with a GnRH antagonist. METHODS AND RESULTS: Based on immunoexpression studies, functional development of Sertoli cells (SGP-2, androgen receptor) and Leydig cells (3 beta-hydroxysteroid dehydrogenase) was detectable at an age (35 weeks) when the testis is considered to be quiescent, and in advance of the pubertal rise in blood testosterone levels (50-60 weeks). Other changes at 35 weeks were the appearance of focal seminiferous tubule lumens and proliferating germ cells [indicated by immunoexpression of proliferating cell nuclear antigen (PCNA)]. Treatment from 25 to 35 weeks with GnRH antagonist largely (>85%) prevented these changes. However, the PCNA-labelling index of spermatogonia in GnRH antagonist-treated animals did not differ from controls (41.3 versus 43.6%) though total spermatogonia volume per testis was reduced by 41%. Some protein markers (inhibin-alpha, estrogen receptor-beta) showed little change with age or treatment. Beyond 35 weeks, GnRH antagonist-treated animals showed a delay in the pubertal rise in plasma testosterone levels. CONCLUSIONS: These findings reinforce the view that the 'childhood' testis is not quiescent. This may explain the damaging effects of some cancer therapies on subsequent fertility of boys and raises the issue of protective intervention. The present studies suggest that GnRH antagonist-based intervention might be only partially successful. Identification of the factors regulating spermatogonial development in the infant marmoset may aid in the design of such strategies.     

The incidence rate,trend and microbiological aetiology of prosthetic joint infection after total knee arthroplasty: A 13 years’ experience from a tertiary medical center in Taiwan

Background/purpose

Total knee arthroplasty (TKA) improves the patient's quality of life by relieving pain, correcting the deformity, and helping the patient resume normal activities. However, post-TKA prosthetic joint infection leads to implant failure, is difficult to treat, and causes a significant burden both economically and health-wise. Therefore, an understanding of the current trends in this infection and microbiology data is essential for preventing and treating it.