Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.

Supplementary Figure 8 - The effects of storage duration (baseline vs. 6 months) on the circulation level of miR-16 in plasma of cases and controls, separately.

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Background: Cervical cancer is a very common gynecological malignancy. The incidence of cervical cancer in Beijing increased rapidly, the local government launched free cervical cancer screening in 2008 as a pilot, and then the program covered all register eligible women in 16 districts since 2009. Our study assessed the free screening program in Beijing from 2008 to 2018. Methods: Analyzed the data of all women aged 35-64 years old who received free cervical cancer screening in Beijing from January 2008 to December 2018. Results: Since 2008, Beijing has conducted five cycles of cervical cancer screening among 35-64 years old women. During the period, target population has adjusted and service management kept on improved. Totally 2,624,129 person times have received the services. The average detection rate of abnormal cervical cytology was 2.3%, the rate of colposcopy referral was 1.8%, and the rate of abnormal colposcopy result was 63.5%. The detection rate of CIN2+ and cervical cancer was 208.5 / 100,000, of which 5228 cases of CIN 2+ were detected, the detection rate of 199.2 / 100,000; 244 cases of cervical cancer were detected and the rate was 9.3 / 100,000. Conclusions: Free cervical cancer screening can effectively serve the grassroots women, improve women's health awareness, and realize the early detection and early treatment of cervical cancer. The coverage of the screening population and the screening strategies need to be further explored to achieve the goal of decreasing cervical cancer incidence and mortality in the future.

目的 对拟参与北京市适龄女性免费子宫颈癌筛查的人乳头瘤病毒(HPV)检测试剂与实验室进行评估.方法 2016年11月至2017年5月期间对自愿参与北京市适龄女性免费子宫颈癌筛查的HPV检测试剂与实验室进行资料审核、实验室质控及样本检测.结果 8种试剂检测HR-HPV、HPV16和18的Kappa值均达到了0.800以上,一致性较好;检测CIN2+的敏感度、特异度、阳性预测值和阴性预测值各组之间相比均无统计学差异(P＞0.05).63.1％的实验室通过了室间质评.8种试剂与6家实验室组合具备参与北京市适龄女性免费子宫颈癌筛查的资质.结论 通过评估分析参与北京市免费子宫颈癌筛查的各种HPV检测方法的临床准确性,掌握了HPV实验室的服务能力,初步筛选出了8种HPV检测试剂和6家PCR实验室承担北京市宫颈癌筛查工作,为完善适龄女性免费子宫颈癌筛查方案提供依据.

Low-cost, accurate high-risk human papillomavirus (HR-HPV) tests are needed for cervical cancer screening in limited-resource settings. More than 200 cervical cytological specimens from hospital patients were collected and analyzed for a real-world study. We evaluated the analytical and clinical performance of four widely used HR-HPV test (Tellgen, Hybribio, Liferiver, and Sansure) based on real-time polymerase chain reaction technology platforms, compared with the cobas test. Cervical intraepithelial neoplasia grade 2 or worse lesions (CIN2+) were set as the disease endpoint, and all the five HPV tests were performed with equal sensitivity (McNemar's test; P = 0.971) and specificity (McNemar's test; P = 0.953). All genotyping using the INNO-LiPA HPV test showed that HPV-16, -52, and -54 were the most common types among CIN2+ cases. Overall, the four HR-HPV tests analyzed appear to be as effective as the cobas HPV test in both agreement and clinical performance. Therefore, each of these low-cost HPV test kits could be implemented in limited-resource settings to accelerate the control of cervical cancer. However, we suggest that there is a need to further standardize and optimize testing around clinical sensitivity and specificity.

Background: To evaluate and compare the results of three different cervical cancer screening strategies including cytology screening, HR-HPV screening which taking HR-HPV testing as primary test and co-testing which taking both tests at the same time, then provide evidence to explore whether the cervical cancer screening can be conducted in community healthcare centers in Beijing. Methods: 182,119 women aged between 35 and 64, who were screened in the primary healthcare facilities of nine districts in Beijing from January 2014 to March 2015, were enrolled in this study. Cytology screening was performed in participants during January 2014 and December 2014 as a conventional arm. HR-HPV screening strategy and co-testing were randomly allocated to participants on districts level as experimental arm 1 and 2 during January 2015 and March 2015. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN 2+) was defined as endpoint. The screening results and costs to detect a case of three strategies were calculated. Results: The positivity rate, colposcopy referral rate and biopsy referral rate of co-testing were 8.46%, 6.36% and 4.65% respectively, which were all significantly higher than the other two screening strategies. The detection rate of CIN 2+ by co-testing was 5.06%o and was much more than the other two screening strategies, while the HR-HPV screening had the highest PPV of 14.40%. The HR-HPV screening ignores some lesion which can be found by co-testing. Co-testing refers a woman to colposcopy with a positive screening result at the least cost, but it costs the most to detect a CIN 2+ case. Conclusions: To detect more cases of CIN 2+, co-testing performs better although with the most cost. And the primary healthcare facilities in Beijing have the capability to carry out the cervical cancer screen programs and prompts women with positive screen results to the hospital. (C) 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences.

This study is to evaluate performances and genotyping capabilities of four human papilloma virus (HR-HPV) tests based on real-time polymerase chain reaction (PCR) technology platforms compared with the cobas test. Discordant results were further analyzed using INNO-LiPA HPV genotyping test, the gold standard laboratory test to determine presence and type of HPV infection. Over 200 samples from Hospital patients were collected and analyzed using five HR-HPV tests. Women with positive test results were referred directly to colposcopy. If a positive result was returned, biopsies were administered for pathological classification. Clinical performances and genotyping capabilities between the four HR-HPV and cobas tests were compared and contrasted. High levels of agreement were observed, though all HR-HPV tests presented discrepancies compared with the cobas test. Cervical intraepithelial neoplasia Grade 2 or higher lesions (CIN2+) was set as the threshold, and all five tests performed with equally high sensitivity. Lower levels of specificity were observed across all five tests. Results suggest the four HR-HPV tests analyzed are as effective as the cobas test in genotyping capacities and diagnosing CIN. Therefore, these test kits should be used for HPV screening, especially in developing nations because they are cost effective and reliable. Minor discrepancies between tests are generally unavoidable though this may add complexity to the clinical decision-making process. As such, we recommend that efforts be made to standardize HPV genotyping tests as well as to optimize clinical sensitivity and specificity. Focusing on these issues will drive the development of HPV detection techniques, therefore save lives.

MicroRNAs (miRNAs) play an important role in regulating cancer stem cell (CSC). Previous studies have shown that microRNA-221/222 (miR-221/222) cluster are involved in the propagation of breast cancer stem cell (BCSC), however, the underlying molecular mechanisms are still not fully understood. In this study, we found that miR-221/222 were overexpressed in highly aggressive breast cancer MDA-MB231 cells, that are enriched in markers for epithelial-mesenchymal transition (EMT) and BCSCs, than in MCF-7 cells. Phosphatase and tensin homolog (PTEN) was confirmed to be the target of miR-221/222 in breast cancer cells. MiR-221/222 enhanced breast cancer cell growth, migration and invasion by downregulating PTEN. Importantly, both ectopic expression of miR-221/222 and PTEN knockdown increased the mammosphere formation capacity and the expression of the stemness marker ALDH1. MiR-221/222 lentivirus vector infected MCF-7 cells produced larger subcutaneous tumors, while shRNA vector of PTEN showed similar trend. Along with the downregulation of PTEN caused by miR-221/222 in the breast cancer cells and the xenograft tumor tissues, Akt phosphorylation (p-Akt), NF-kappa p65 and phosphorylated p65 (p-p65), and cyclooxygenase-2 (COX-2) were all overexpressed compared to the negative control. Taken together, our findings indicate that miR-221/222 play a critical role in the propagation of BCSCs and tumor growth possibly through targeting PTEN, which in turn activating the Akt/NF-kB/COX-2 pathway. MiR-221/222 might represent the potential target of breast cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.

This arcticle has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13287-016-0438-5.