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

将通过开发一种低成本的护理点设备来应对宫颈癌早期检测的挑战，该设备有可能改善发达国家和发展中国家患者的临床结果，同时克服与筛查接受和有限的基础设施有关的关键障碍，这些障碍迄今为止一直阻碍着进展。由人乳头瘤病毒（HPV）的某些基因型引起的宫颈癌是全球女性中第四大最常见的癌症，2018年诊断出约570，000例新病例;低收入和中等收入国家报告的死亡中有90%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10万名妇女中有6.8人死亡。疫苗接种和筛查有可能将全球宫颈癌的发病率降低到每10万名妇女中有4人。最近，由于对采样收集程序和文化障碍等问题的担忧，基于细胞学的筛查的采用率已降至80%以下。个性化医疗和生物传感技术的最新进展已经影响了从基于细胞学的筛查和HPV检测到HPV诊断的范式转变，这需要先进的仪器，集中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品中的低水平灵敏度和特异性、系统集成和信号读出要求在内的挑战，很少有生物传感器设备从研究实验室转化为临床使用。目前，没有世界卫生组织的资格预审HPV检测。因此，我们现在建议建立一个跨学科的英国-南非伙伴关系，将化学，工程，生物医学科学和医学的研究人员聚集在一起，以开发快速诊断工具。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，它们与分子（即，HPV-16和HPV-18基因型的早期检测，具有更高的灵敏度、特异性和更短的检测时间（< 10分钟）。电化学传感层将使用低成本和容易获得的矿物质，如锰，铜和钛。通过这种电化学传感的荧光检测方法，可以将高风险基因型的低成本荧光检测纳入人群筛查。总之，这种跨学科的伙伴关系旨在促进高危HPV基因型的早期检测，特别是在基础设施有限和吸收率下降的发展中国家和发达国家，同时改善健康和福祉，这是第三个联合国可持续目标。

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.