Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre‐malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR‐20a, miR‐92a, miR‐141, miR‐183*, miR‐210 and miR‐944) were found to be significantly up‐regulated in cervical cancer and pre‐malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre‐malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low‐grade lesions, high‐grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre‐malignant lesions and cancer in the near future.

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We conducted a prospective randomized controlled trial with two screening rounds to evaluate the effectiveness of combining HPV testing with liquid‐based cytology (LBC) as a co‐test, compared to LBC only in cervical cancer screening of a Chinese population. First, 15,955 women aged 30–60 were randomized at a 1:1 ratio into an intervention group (Digene Hybrid Capture 2 HPV test with LBC) and a control group (LBC alone). Women in the intervention group would be referred for colposcopy and biopsy immediately if they were found to have high‐risk HPV regardless of cytology results. The detection of cervical intraepithelial neoplasia grade 2 or above (CIN2+) lesions was significantly higher in the intervention group compared to the control (0.95% vs. 0.38%, OR 2.50, 95% CI 1.65–3.88). At the subsequent round of screening approximately 36 months later, CIN2+ detection was significantly lower in the intervention group (0.08% vs. 0.35%, OR 0.23, 95% CI 0.08–0.57). Over the two rounds of screening, the total detection of CIN2+ was higher in the intervention group (1.01% vs. 0.66%, OR 1.53, 95% CI 1.09–2.19). There was a fourfold increase (10.6% vs. 2.4%, p < 0.001) in the number of colposcopies performed in the intervention arm. Adding a high‐risk HPV test to cytology for primary cervical screening led to earlier detection of clinically significant preinvasive lesions, resulting in a reduced detection of CIN2+ lesions in subsequent rounds and an increased rate of colposcopy.

Background and Objectives:Ischemic stroke despite direct oral anticoagulant (DOAC) is increasingly common and portends high risk of subsequent ischemic stroke. Efficacy and safety of antithrombotic regimens following the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOAC with and without an alternative antithrombotic regimen, and determine the risk factors of recurrent ischemic stroke while on anticoagulation.Methods:In a population-based, propensity-score weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOACswitch) or addition of antiplatelet agents, with unchanged DOAC regimen (DOACsame) among non-valvular atrial fibrillation (NVAF) patients who developed the first ischemic stroke despite DOAC from 1stJanuary 2015 to 31stDecember 2020 in Hong Kong. Primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome and death. We performed competing risk regression analyses to compare the clinical endpoints, and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model.Results:During the 6-year study period, among 45,946 AF patients on DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite DOAC. 2,337 NVAF patients were included in the final analyses. Compared to DOACsame, warfarin (aHR 1.96, 95%CI 1.27-3.02, p=0.002) and DOACswitch(aHR 1.62, 95%CI 1.25-2.11, p-value <0.001) were associated with increased risk of recurrent ischemic stroke. In DOACsamegroup, adjunctive antiplatelet agent was not associated with reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke.Discussion:In NVAF patients with ischemic stroke despite DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not appear to reduce ischemic stroke relapse. As diabetes mellitus, use of CYP/P-gp modulators and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate if strict glycemic control, DOAC level monitoring and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients.Classification of Evidence:This study provides Class II evidence that in patients with non-valvular atrial fibrillation suffering an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.

High-risk human papillomavirus (HR-HPV) testing has become an increasing important strategy in primary cervical cancer screening in recent years. It warrants the evaluation of molecular-based HPV tests for accuracy and efficacy of screening. The performance of Roche Cobas 4800 HPV test was validated and compared with Digene Hybrid Capture 2 (HC2) high-risk HPV DNA test for primary screening in a large Chinese screening cohort. Of 6345 women screened, overall agreement between Cobas and HC2 was 92.23% (95% CI: 91.57–92.89). The inter-assay agreement was correlated with the severity of underlying biology, with an increasing concordance found in samples with more severe abnormalities. Most of the discordant samples had the test signal strength closer to the test limits of the detection than concordant samples, reflecting a low viral load and infection of a cluster of low-risk HPV in these samples. The Cobas test demonstrated significantly higher specificity in identifying CIN2+/CIN3+ cases than HC2 test (66.46% vs 43.67% and 65.42% vs 42.86%, p<0.001), with comparable sensitivity in clinical evaluation. Increased specificity of Cobas test would accent women having the highest risk of developing CIN2+, with the potential to reduce unnecessary colposcopy referral in a screening population.

The aim of this study was to assess the effectiveness of HPV self-sampling for cervical cancer screening and the best means of service delivery, with a specific focus on under-screened women, particularly during the COVID-19 pandemic. Using three arms of service delivery (social media, school outreach and underserved outreach), we recruited under-screened women aged 30–65 years from two population groups: the general public and specific underserved communities, from whom self-sampled specimens and optional clinician-sampled cervical specimens were obtained for HPV testing. A total of 521 self-sampling kits were distributed, of which 321 were returned, giving an overall uptake rate of 61.6%. The response rate was higher in the face-to-face underserved outreach (65.5%) compared to social media (22.8%) and school outreach (18.2%). The concordance for HPV detection between self-sampled and clinician-sampled specimens was 90.2% [95% confidence interval (CI) 85.1–93.8%; Cohen’s kappa 0.59 (95% CI 0.42–0.75)]. Overall, 89.2% of women were willing to have self-sampling again. In conclusion, HPV self-sampling is an effective method for cervical cancer screening and can be considered as an option, particularly in women who are reluctant or unable to attend regular screening. Various service deliveries could be considered to increase participation in cervical cancer screening.

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This study aimed to assess the feasibility of patient-initiated follow-up (PIFU) in combination with regular tumour marker monitoring as an alternative to conventional hospital follow-up for ovarian cancer survivors. Women who had recently completed treatment for ovarian cancer and had a raised pre-treatment tumour marker were recruited. Participants were allocated to PIFU (intervention group) or conventional hospital follow-up (control group) according to their own preference. Both groups had regular tumour marker monitoring. The change in fear of cancer recurrence (FCR) score as measured by the FCR inventory, and the supportive care need (SCN) scores as measured by the SCN survey at baseline and at 6 months between PIFU and hospital follow-up were compared. Out of 64 participants, 37 (58%) opted for hospital follow-up and 27 (42%) opted for PIFU. During the 6-month study period, there was no significant difference in the change of FCR between the two groups (p = 0.35). There was a significant decrease in the sexuality unmet needs score in the intervention group from baseline to 6-month FU (mean difference −8.7, 95% confidence interval −16.1 to −1.4, p = 0.02). PIFU with tumour marker monitoring is a feasible follow-up approach in ovarian cancer survivorship care. FCR and SCN were comparable between PIFU and conventional hospital follow-up.