Cervical cancer prevention among long-term screening non-attendees by vaginal self-collected samples for hr-HPV mRNA detection.
通过阴道自我收集样本进行 hr-HPV mRNA 检测，在长期筛查非参与者中预防宫颈癌。
- 作者列表："Ernstson A","Urdell A","Forslund O","Borgfeldt C
Background:The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample. Methods:A vaginal self-sampling kit was sent to 6023 women aged 30-70 years who had not provided a cervical screening sample for ≥7 years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14 months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons. Results:The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4-14.1%] and 9.9% [(79/796), 95% CI 7.9-12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6-2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1-1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed. Conclusions:Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.
背景: 宫颈癌筛查项目的疗效取决于参与率。为了增加未参加宫颈癌筛查的妇女的参与度，自行收集用于检测高危型人乳头瘤病毒 (hr-HPV) 的样本可能是一种选择。本研究的目的是: 调查向长期未参加者发送自行收集的阴道样本进行 hr-HPV mRNA 检测的反应率;自我样本中 HPV 阳性的女性对随访的依从性; 宫颈不典型增生 (高度鳞状上皮内病变 (HSIL)) 的患病率, 应答者中不能排除 HSIL (ASC-H) 或原位腺癌 (AIS)) 或癌症的非典型鳞状细胞;以及探索不返回自我样本的原因。 方法: 将阴道自我取样试剂盒发送给 6023 名年龄在 30-70 岁之间的妇女，这些妇女在 sk？Ne 地区 ≥ 7 年没有提供宫颈筛查样本, 11月和 2017年12月的瑞典。通过 Aptima HPV mRNA 检测 (Hologic) 分析自身样本。不迟于 2018年5月31日返回的所有阴道自我样本均纳入研究。结果随访至 2019年1月31日，随访时间变化在 8 至 14 个月之间。Hr-HPV mRNA 阳性的女性被邀请进行随访检查。该检查包括用于细胞学分析的宫颈样本和更新的 Aptima HPV mRNA 检测。随机抽取未返回自我样本的女性 200 名进行电话访谈，以探讨其原因。 结果: 自行收集的阴道 hr-HPV 样本的有效率为 13.2% [(797/6023)，95% CI 为 12.4-14.1%] 和 9.9% [(79/796), 95% CI 7.9-12.2%] hr-HPV mRNA 阳性。全组应答者中重度异型增生或癌的患病率为 1.3% [(10/796)，95% CI 0.6-2.3%]，宫颈癌患病率为 0.4% [(3/796), 95% CI 0.1-1.1%]。只有 27 名妇女参加了电话访谈，没有观察到不返回自我样本的特殊原因。 结论: 自我收集的阴道 hr-HPV 样本增加了长期非参与者对宫颈癌筛查的参与。长期非参与者的宫颈癌患病率几乎是有组织筛查人群的 7 倍。
METHODS::Altered aerobic glycolysis is an important feature of cancer cell energy metabolism, known as the Warburg effect. Cervical cancer is one of the most common causes of cancer death in females. However, the roles of aerobic glycolysis in the development of cervical cancer are still poorly defined. Here, we identified a transcription factor (TF), ETS-related gene (ERG), as a new regulator of cancer progression and the glycolysis process in cervical cancer. In this study, we found that ectopic expression of ERG enhanced the capacity of aerobic glycolysis and increased glucose uptake, lactate production, and ATP generation. ERG overexpression increased and ERG knockdown decreased the anchorage independent cell growth and cell invasion in cervical cancer cells. Mechanistically, we propose that ERG regulates the expression of hexokinase 2 (HK2) and phosphoglycerate kinase 1 (PGK1) in the glycolytic pathway by directly binding to their promoters. A gain-of-function study showed that the knockdown or overexpression of HK2 and PGK1 abolished the increased or decreased aerobic glycolysis and cervical cancer progression induced by stable ectopic expression or depletion of ERG, respectively. Taken together, our findings suggest that ERG plays a potential role in the progression of cervical cancer, and could serve as a novel biomarker and potential therapeutic target in cervical cancer.
METHODS:INTRODUCTION:Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS:De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS:Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS:HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.
METHODS::Human papillomavirus (HPV) type 58 is the third most commonly detected HPV type in cervical cancer among Eastern Asians. Our previous international epidemiological studies revealed that a HPV58E7 natural variant, T20I/G63S (designated as V1), was associated with a higher risk of cervical cancer. We recently showed that V1 possesses a greater ability to immortalise and transform primary cells, as well as degrading pRB more effectively than the prototype and other common variants. In this study, we performed a series of phenotypic and molecular assays using physiologically relevant in vitro and in vivo models to compare the oncogenicity of V1 with that of the prototype and other common natural variants. Through activation of AKT and K-Ras/ERK signalling pathways, V1 consistently showed greater oncogenicity compared with prototype and other variants, as demonstrated by increased cell proliferation, migration and invasion, as well as induction of larger tumours in athymic nude mice. This study complements our previous epidemiological and molecular observations pinpointing the higher oncogenicity of V1 compared with prototype and all other common variants. Since V1 is more commonly found in Eastern Asia, our report provides insight into the design of HPV-screening assays and selection of components for HPV vaccines in this region.IMPORTANCE Epidemiological studies have revealed that a wild type variant of HPV58 carrying an E7 variation, T20I/G63S (V1), is associated with a higher risk of cervical cancer. We previously reported that this increased oncogenicity could be the result of its greater ability to degrade pRB, thereby leading to an increased ability to grow in an anchorage-independent manner. In addition to this, this report further showed that this HPV variant induced activation of AKT and K-Ras/ERK signalling pathways, thereby, explaining its genuine oncogenicity in promoting cell proliferation, migration, invasion, and formation of tumours, all to a greater extent than prototype HPV58 and other common variants.