Validating the Use of Point-Of-Care Diagnostics for Early Detection of Human Papillomavirus

宫颈癌的早期检测挑战将通过开发一种低成本的护理点(PoC)设备来解决，这种设备有可能改善发达国家和发展中国家患者的临床结果，同时克服与筛查吸收和有限的基础设施有关的关键障碍，这些障碍迄今阻碍了进展。由某些类型的人乳头瘤病毒(HPV)引起的宫颈癌是全球妇女中第四常见的癌症，2018年新诊断病例约为57万例；在低收入和中等收入国家，报告的90%的死亡与有限的预防、筛查和治疗选择有关。欧洲的死亡率估计为每10万名妇女中有6.7人死亡，而全球死亡率为每10万人中有6.8人死亡。接种疫苗和筛查有可能将全球宫颈癌发病率降至每10万名妇女4人。最近，由于对采样收集程序和文化障碍等方面的担忧，基于细胞学的筛查的接受率已降至80%以下。个性化医学和生物传感技术的最新进展影响了从基于细胞学的筛查和HPV检测向PoC诊断的范式转变，这些检测需要先进的仪器、集中化的实验室和经验丰富的操作员。然而，由于克服了包括临床样本的低灵敏度和特异度、系统集成和信号读出要求等挑战，很少有PoC设备从研究实验室转化为临床使用。目前，世界卫生组织还没有对HPV检测进行资格预审的PoC检测。因此，我们现在建议英国和南非建立跨学科伙伴关系，将化学、工程、生物医学和医学的研究人员聚集在一起，这是开发快速POC诊断工具所必需的。我们的合作研究方法将使我们能够开发基于纳米材料的信号放大器和氧化还原标签，这些标签与PoC诊断中的分子(即蛋白质和DNA)生物传感平台兼容，用于早期检测高危HPV-16和HPV-18基因，提高了灵敏度、特异性和检测时间(&lt；10分钟)。电化学传感层将使用低成本和容易获得的矿物，如锰、铜和钛来开发。通过这种通过电化学传感进行PoC检测的方法，可以将针对高危基因类型的低成本PoC检测纳入人群筛查。总而言之，这一跨学科伙伴关系寻求促进高危HPV基因型的早期检测，特别是在基础设施有限且吸毒率不断下降的发展中国家和发达国家，同时改善健康和福祉，这是联合国可持续发展的第三个目标。

The early detection challenge of cervical cancer will be addressed through the development of a low-cost, point-of-care (PoC) device that has the potential to improve clinical outcomes for patients in both developed and developing countries while overcoming key barriers linked to screening uptake and limited infrastructure, which has impeded progress till date. Cervical cancer caused by certain genotypes of human papillomavirus (HPV) is the fourth most frequent cancer among women globally with approximately 570,000 new cases diagnosed in 2018; where 90% of deaths reported in low and middle-income countries are linked to limited prevention, screening, and treatment options. The mortality rate was estimated at 6.7 per 100 000 women in Europe compared to global mortality rate of 6.8 per 100 000 women. Vaccination and screening have the potential to reduce the incidence rate of cervical cancer to 4 per 100 000 women globally. Recently, the uptake of cytology-based screening has fallen below the 80% standard due to concerns about the sampling collection procedure and cultural barriers, among others. Recent advances in personalized medicine and biosensing technologies has influenced the paradigm shift to PoC diagnostics from cytology-based screening and HPV testing that require advanced instrumentation, centralized laboratories, and experienced operators. However, few PoC devices have been translated from research laboratories to clinical use, due to overcoming challenges including low levels of sensitivity and specificity in clinical samples, system integration and signal readout requirements. Currently, there are no World Health Organisation prequalified PoC tests for HPV detection. We therefore now propose an interdisciplinary UK-South Africa partnership bringing together researchers from chemistry, engineering, biomedical science, and medicine necessary to develop rapid PoC diagnostic tools. Our collaborative research approach will allow us to develop nanomaterials-based signal amplifiers and redox tags that are compatible with molecular (i.e., proteins and DNA) biosensing platform used in PoC diagnostics for early detection of high-risk HPV-16 and HPV-18 genotypes with improved sensitivity, specificity, and low detection time (< 10 minutes). The electrochemical sensing layer will be developed using low-cost and readily available minerals such as manganese, copper, and titanium. Through this approach of PoC testing via electrochemical sensing; low-cost PoC testing for high-risk genotypes can be incorporated into population screening. In summary, this interdisciplinary partnership seeks to facilitate the early detection of high-risk HPV genotypes, especially in both developing and developed countries with limited infrastructure and declining uptakes rates, respectively, while improving health and well-being which is the third UN Sustainable Goal.