PAX1/SOX1 DNA Methylation Versus Cytology and HPV16/18 Genotyping for the Triage of High-Risk HPV-Positive Women in Cervical Cancer Screening: Retrospective Analysis of Archival Samples.

OBJECTIVE: To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high-risk HPV-positive cervical samples. DESIGN: Retrospective analyses of archival samples collected from a large-scale prospective randomised controlled trial. SETTING/SAMPLE: HPV-positive women recruited from the general cervical screening population. METHODS: 403 HPV-positive samples including 113 normal, 173 low-grade cervical intraepithelial neoplasia (LG-CIN), 114 HG-CIN and three cervical cancers. All samples were assessed by liquid-based cytology, HPV genotyping and PAX1/SOX1 methylation. MAIN OUTCOME MEASURES: AUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high-grade (HG) premalignant cervical lesions. RESULTS: PAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5-81.5), 41.9% (95% CI: 32.9-50.8), 48.7% (95% CI: 39.7-57.8) and 36.8% (95% CI: 28.0-45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0-75.6), 83.6% (95% CI: 79.3-87.9), 77.6% (95% CI: 72.8-82.5) and 67.1% (95% CI: 61.7-72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty-two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively). CONCLUSION: PAX1 triage for referral to colposcopy in HPV-positive women may be superior to cytology and HPV16/18 genotyping.

Evaluation of an Isothermal Amplification HPV Assay on Self-Collected Vaginal Samples as Compared to Clinician-Collected Cervical Samples.

This study aimed to evaluate the concordance of HPV results between the SentisTM HPV assay (Sentis) (BGI Group, Shenzhen, China), an isothermal amplification-based HPV assay, on self-collected and clinician-collected samples and the agreement of Sentis on self-collected samples with the BD OnclarityTM HPV assay (Onclarity) (Becton, Dickinson, and Company, Franklin Lakes, New Jersey, USA), a PCR-based HPV assay, on clinician-collected samples. This was a prospective study of 104 women attending the colposcopy clinic for abnormal smears. After informed consent, participants self-collected vaginal samples before having clinician-collected cervical samples. Self-collected samples underwent HPV testing with Sentis (Self-Sentis HPV) and clinician-collected samples were tested with Sentis (Clinician-Sentis HPV) and Onclarity (Clinician-Onclarity), which was used as a reference standard. The concordance was assessed using Cohen's kappa. The prevalence of HPV and the acceptability of self-sampling were also evaluated. The concordance rate between Self-Sentis HPV and Clinician-Sentis HPV was 89.8% with a kappa of 0.769. The concordance rate between Self-Sentis HPV and Clinician-Onclarity was 84.4% with a kappa of 0.643. The prevalence of HPV was 26.0% on Clinician-Onclarity, 29.3% on Clinician-Sentis HPV, and 35.6% on Self-Sentis HPV. Overall, 65% of participants would undergo self-sampling again. This was attributed to mainly not feeling embarrassed (68%) and being convenient (58%). Our study showed a substantial agreement between Self-Sentis HPV with Clinician-Sentis HPV and Clinician-Onclarity. Self-sampling was also shown to be a generally well-accepted method of screening.

Patient-Initiated Follow-Up in Ovarian Cancer.

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.

Outcome after loop electrosurgical excision procedure for cervical high-grade squamous intraepithelial lesion.

OBJECTIVE: The dilemma in treating cervical high-grade squamous intraepithelial lesion (HSIL) is how to achieve complete excision to minimize the risk of cervical cancer while sparing the anatomy of the cervix and its ability to function during pregnancy. The optimal management for positive margins after excisional treatment is still controversial. This study was conducted to determine the clinical and histologic predictors of residual/recurrent HSIL and assess the outcome of women with positive margin. MATERIALS AND METHODS: This retrospective cohort study included 386 women who had excisional treatment for HSIL during 1st January 2012 to 31st December 2015 in a university-affiliated hospital. RESULTS: Overall, 212 (54.9%) women had negative margins and 155 (40.2%) had positive margins. The cumulative rate of residual/recurrent HSIL at 2 and 5 years was 15.7% and 16.8% respectively in positive margins and 1.8% and 5.0% respectively in negative margins (p < 0.001). Of women who had residual/recurrent HSIL, significantly more women had positive margins compared to negative margins (74.1% vs 25.9%, p = 0.001). Positive margin was significantly associated with higher rate of subsequent abnormal cervical smear (48.2% vs 28.9%, p < 0.001), requiring further colposcopy (32.1% vs 14.4%, p < 0.001) and further treatment for SIL (7.5% vs 4.8%, p < 0.001) compared to negative margin. CONCLUSION: Most women (85%) with positive margin went without residual/recurrent HSIL, of which the option of close surveillance with cytology is reasonable. Repeat excision may be considered in selected women with positive margin, endocervical glandular involvement and those who are older or unable to comply with follow-up.

Clinical performance of the Roche Cobas 4800 HPV test for primary cervical cancer screening in a Chinese population.

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.

Human Papillomavirus Self-Sampling for Primary Cervical Cancer Screening in Under-Screened Women in Hong Kong during the COVID-19 Pandemic.

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.

Primary HPV testing with cytology versus cytology alone in cervical screening-A prospective randomized controlled trial with two rounds of screening in a Chinese population.

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.

Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

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.

Anti-acetylcholinesterase activities of traditional Chinese medicine for treating Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.