Journal of Medical Virology最新文献

High-risk human papillomavirus (hrHPV)-genotype specific risk stratification may improve cervical screening efficiency. This study evaluates the risks of cervical intraepithelial neoplasia (CIN), cancer and unnecessary referrals by hrHPV-genotype in cytology-positive (ASCUS+) women, using data from the Dutch population-based cervical screening program. Data from hrHPV+/ASCUS+ women screened between January 2017 and March 2018 were analyzed using the Dutch Screening and Pathology databases. Risks for CIN2+/3+, cancer, and unnecessary referral (i.e., without CIN2+) were evaluated by hrHPV-genotype (HPV16, HPV18, hrHPV-other (i.e., non-16/18 hrHPV), or mixed HPV16/18) using logistic regression, adjusted for age, laboratory (as proxy for region), sampling method (self- vs. clinician sampling), and stratified by age (< 50/≥ 50 years). HPV16+ women had 3.7 (CI: 3.42–3.95) and 4.6 (CI: 4.24–4.99) times higher risks of CIN2+ and CIN3+, respectively, compared to hrHPV-other. HPV18+ women had 1.6 (CI: 1.43–1.79) and 1.9 (CI: 1.68–2.18) times higher risks. The cervical cancer risk was tenfold higher for both HPV16 (OR: 9.85, CI: 6.50–14.95) and HPV18 (OR: 10.27, CI: 6.33–16.68). Women with HPV16 had 70% and HPV18 40% lower risks of unnecessary referral, compared to hrHPV-other. All risk differences between HPV16 or HPV18 and hrHPV-other were statistically significant in both age groups (< 50 and ≥ 50 years). Given the significantly higher risk of CIN2+/3+ and cancer associated with HPV16 and HPV18 and the reduced likelihood of unnecessary referrals compared to hrHPV other, these findings support the use of genotype-based colposcopy referrals in cervical screening to enhance screening efficiency.

High risk human papillomaviruses (hrHPVs) cause most cervical cancers. Cervical screening programmes aim to identify precancerous disease using detection of hrHPV nucleic acid using clinician-taken liquid-based cytology (LBC) samples, or increasingly, self-taken samples (STSs). However, STSs are incompatible with traditional cytology triage. Therefore, development of novel triage tests is essential. Quantification of cellular and viral mRNA biomarkers is one option, but little is known about mRNA quality in STSs. We extracted RNA from two sets of STSs (reflecting separate sampling devices) from the Scottish HPV Archive (SHA) and the Swedish Cervical Cytology Biobank (SCCB). We investigated whether the ACTB, GAPDH and p16 RNAs could be amplified by reverse transcription quantitative PCR (RT-qPCR). RNA was degraded in both sets of samples, but samples from the Scottish HPV Archive were generally suitable for RT-qPCR analysis, while samples from the SCCB were mostly unsuitable. Genomic DNA contamination was detected in 11.6% of samples. The quantity and quality of RNA derived from STSs was unaffected by storage of the original sample at −70°C for a period of 1 year. These data suggest that feasibility of utilising STSs for mRNA expression work is device-dependent and that optimisation of collection and storage systems is warranted.

High-risk human papillomavirus (hrHPV) infection is the primary cause of cervical cancer. However, hrHPV testing lacks specificity in detecting neoplastic changes. This study explored the utility of quantitative methylated HPV DNA markers for precise detection of cervical lesions. Using hybridization capture-based bisulfite sequencing, we analyzed genome-wide HPV methylation patterns. The study included a training cohort of 60 cervical exfoliated cell samples and a validation cohort of 29 samples. Analysis of 112 CpG sites across the HPV genome revealed that genome-wide HPV16 methylation levels correlated with disease progression. Squamous cell carcinoma (SCC) showed 1.4-fold higher methylation levels compared to normal tissue (p = 0.0032). Progressive methylation increases in the E5-α and L2 genes were observed across the spectrum of cervical lesion severity, from normal tissue through high-grade squamous intraepithelial lesion (HSIL) to SCC. Intersection analysis of differentially methylated CpG sites between HSIL vs Normal and SCC vs Normal identified 16 consistently hypermethylated CpG sites in the E5-α, E7, L2, and L1 genes, distinguishing both HSIL and SCC from normal tissue. This pilot study identifies a five-CpG methylation panel (E5-α_3887, E5-α_3941, E7_701, L2_4441, and L2_5128) as promising triage biomarkers for HPV16-positive women, achieving high discriminatory performance (AUC = 0.919 in a validation cohort) for detecting cervical lesions. This genome-wide capture sequencing identified novel HPV16 methylation markers that distinguish cervical lesions from normal tissue, supporting the feasibility of HPV methylation-based triage for HPV-positive women in cervical cancer screening.

Cytomegalovirus (CMV) infection is a prevalent complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, posing significantly impact on clinical outcomes and healthcare costs. This study aims to assess the clinical and economic burden of CMV infection in hospitalized adult allo-HSCT recipients in China. A retrospective analysis was conducted using electronic medical records from two tertiary hospitals in China. A total of 1977 patients who underwent allo-HSCT while hospitalized between 1 January 2016 and 31 December 2021 were included in the study and followed up for 180 days. Data on CMV clinical characteristics, hospitalization duration, complications, and healthcare costs were collected and analyzed. CMV infection/disease was observed in 542 patients during the hospitalization of the allo-HSCT procedure, leading to longer hospital stays (69.36 [SD 23.15] vs 37.77 [SD 13.22] days, p < 0.001) and increased medical expenses (US$60,152.98 [SD 30,190.82] vs $34,430.88 [17,723.65], p < 0.001). Patients with CMV infection/disease had higher rates of complications, such as graft-versus-host disease (52.21% vs 19.65%, p < 0.001), and required more extensive use of granulocyte colony-stimulating factor, red blood cell and platelet transfusion, antifungals drugs, and antibacterials drugs. CMV infection/disease imposes significant clinical and economic burdens on hospitalized allo-HSCT recipients in China. Effective monitoring and prevention strategies are essential to mitigate these impacts, improve patient outcomes, and reduce healthcare costs.

The devastating clinical, psychological, and economic impact of the COVID-19 pandemic, caused by global spread of the second Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has engendered a massive response from the scientific community to rapidly understand the biology of SARS-CoV-2 and to develop interventions to prevent infection or progression to life-threatening disease. Angiotensin converting enzyme-2 (ACE2) and its interaction with the SARS-CoV-2 Spike glycoprotein, which mediates fusion of the virion envelope with the target cell membrane, have emerged as a major pharmacological target, as disruption of the Spike-ACE2 interaction prevents cells from becoming infected and hence from producing viral progeny. Moreover, the dysregulation of ACE2 that occurs in the context of SARS-CoV-2 infection may have broader implications for COVID-19 pathogenesis. Here we summarize the role of ACE2 as a physiologic regulator of human health, as a facilitator of SARS-CoV-2 infection, as a factor in COVID-19 disease, and as a target for pharmacological interventions.