Project Description
Early detection for cervical cancer
Background of Research
What is Cervical Cancer?
Cervical Cancer is cancer that starts in the cells of the cervix. The cervix is lower, narrow end of the uterus. The cervix connects the uterus to the vagina. Cervical cancer usually develops slowly over time. If not destroyed or removed, the abnormal cells may become cancer cells and start to grow and spread more deeply into cervix and to surrounding areas.
The most common cause of cervical cancer is persistent infection caused by the sexually transmitted Human Pailoma Virus. HPV is accountable for 90‑100% of cervical cancer cases amongst women, especially those < 35 years old [2].
Every year, half a million women worldwide are diagnosed with cervical cancer, with half of those diagnosed dying as a result. Cervical Cancer is strongly linked to socioeconomic development, with the disease affecting low- and middle-income countries disproportionately.
Cervical Cancer is more Common than you Think
In Korea, according to data from the Central Cancer Registration Headquarters of the Ministry of Health and Welfare released in 2022, [3] It is a cancer with a high incidence rate and the number of patients among all female cancers in Korea. Cervical cancer has a higher proportion of young patients than other carcinomas. According to the "2019 National Cancer Registration Statistics," [4] cervical cancer ranked third in crude incidence, following thyroid cancer and breast cancer in women aged 15 to 34. In addition, despite the overall improvement in the screening rate for four major carcinomas, the screening rate for cervical cancer has recently decreased.
Cervical cancer has a similar pattern around the world. According to WHO's 2020 statistics [5] Cervical cancer is the fourth most common female cancer in the world, with deaths occurring mainly in low- and middle-income countries.
Cervical Cancer incidence in Low- to middle- income countries
In 2010, Bruni et al [7] reported a 4‑fold higher prevalence of cervical cancer in LMICs compared with that in developed countries. In countries ranked low in the Human Development Index, cervical cancer is ranked as the second most common type of cancer and the second highest cause of cancer‑relatedmortality amongst women after breast cancer. In Africa, cervical cancer is the most commonly diagnosed type of cancer and the leading cause of cancer‑related death among women.
80-90% of cervical cancer patients a year occur in low‑ and middle‑income countries (LMICs) because other factors that contribute to the incidence of cervical cancer include geography, screening levels, socioeconomic status, healthcare access, public awareness, smoking and co-infection with HIV [4].
Women in low and middle-income countries may not receive prophylactic vaccines or screening due to a lack of adequate logistics and infrastructure, as well as a lack of trained medical services and health education. Aside from political and social issues. It is critical to address these issues and devise strategies to overcome these obstacles. It is necessary to address the social, political, and economic barriers to accessing services, particularly those related to gender.
Current Cervical Cancer screening
The goal of screening for cervical cancer is to find percancerous cervical cell changes, when treatment can prevent cervical cancer from developing. Sometimes, cancer is found during cervical screening. Cervical cancer found at an early stage is usually easier to treat. By the time symptoms appear, cervical cancer may have begun to spread, making treatment more difficult.
There are 2 main ways to screen for cervical cancer :
HPV test : Check cells for infection with high-risk HPV types that can cause cervical cancer.
Pap test : Collects cervical cells so they can be checked for changes caused by HPV that may turn into cervical cancer.
Cervical cancer screening tests are usually done during a pelvic exam. During the exam, you lie on your back on an exam table, bend your knees, and put your feet into supports at the end of the table. The health care provider uses a speculum to open your vagina to see the cervix. A narrow brush or tiny spatula is used to collect a small sample of cells from your cervix.
Cervical screening test results usually come back from the lab in about 1-3 weeks.
Regular Check-up of Cervical Cancer is difficult & burdensome
The most representative symptom of cervical cancer is vaginal bleeding, which can be mistaken for menstruation. Cervical cancer has no symptoms at all in the early stages, and symptoms only occur after the cancer has progressed to some extent. Therefore, if cervical cancer diagnosis and treatment are not performed at the time of vaginal bleeding, the patient's prognosis may deteriorate significantly. It is very important to diagnose cervical cancer, which has a high incidence not only in Korea but also worldwide, at the beginning of the outbreak. In order to diagnose cervical cancer at the beginning of the outbreak, the method is to 'diagnose regularly'.
The most obvious way to diagnose cervical cancer early is 'regular check-up'. However, regular cervical cancer checkups can be very economically burdensome, and takes a long time for the result.
Problem Solving
In order to solve the importance of early diagnosis of cervical cancer and the accompanying economic cost problem mentioned in Background Research, this project was launched to develop a sensor that can diagnose cervical cancer early using synthetic biology.
For the periodic diagnosis of cervical cancer, it came up with the concept of a "period" that women are most familiar with and can encounter periodically, and aims to allow women to diagnose cervical cancer early at a very simple, periodic and low cost by embedding an aptamer-based biosensor in a sanitary pad-type pad. By using physiological phenomena that always occur in women, we want to develop a complete non-invasive cancer sensing sensor beyond minimally invasive sensing. Also, we want to embrace women in diagnostic blind spots who cannot pay high diagnosis costs by visiting hospitals periodically.
We decided to call this pad "CEApture". The reason we named it CEApture is because it is a sensor that captures CEA protein, a biomarker for cervical cancer, with N56 aptamer.
1. Setting up diagnostic principles
We diagnose cervical cancer using biomarkers that can identify cervical cancer and aptamers specific to it. At this time, the LFA method will be used as “CEApture” principle. The lateral flow assay (LFA) is a paper-based platform for the detection and quantification of analyte in complex mixtures.
The biggest feature of the LFA-type sanitary napkin sensor “CEApture” is that it utilizes the bleeding phenomenon that naturally occurs in women, although minimal blood collection is required for minimally invasive biosensors such as blood sugar sensors. Of course, scientifically verifying the feasibility of this idea is difficult, but we did it.
The reason why we used an aptamer rather than an antibody for the LFA sensor is as follows.
Aptamers are synthetic molecules that can be produced inexpensively. This was important because we wanted to develop diagnostic technology that was accessible to all people, regardless of economic disparity.
Aptamers are smaller and more flexible than antibodies.
Aptamers are easy to immobilize on nanoparticles or test lines of LFA sheet.
2. Scientific Embodiment and Verification
Dry lab
By using HDOCK, we selected N56 DNA aptamer among the CEA protein specific aptamer candidates in the research paper [5], because of its highest binding affinity to CEA protein. More detailed and in-depth information is in the ( Model ) of the wiki.
Wet lab
In the wet lab, we attempted to find a protein-aptamer pair suitable for LFA system through Protein-Aptamer Docking (PAD) experiment and H-NMR spectroscopy. PAD experiment is a method that allows you to visually check binding pattern of aptamer-protein complex. Simply checking the presence or absence of binding is not enough to say that it is an aptamer that can be used in LFA. This is because there is a possibility that it is not a binding pattern that can be used for LFA. Through a scientific verification process, it was proven that CEA protein and N56 aptamer are a suitable pair for LFA sensor. We are the first to report to 2023 iGEM as PAD image results for CEA-N56 aptamer binding complex that have not been reported anywhere until now. If you are curious about the actual PAD image and detailed information, you can check Experiments and Results of the wiki.
3. Expected effects of Research
Through scientific experiments, we analyzed and visualized the binding pattern of CEA protein and N56 aptamer, experimentally proving that they are a suitable pair for LFA sensor.
It is expected that this research will be able to improve the quality of life of people who have financial difficulties and cannot go to the hospital frequently.
Because it is a completely non-invasive sensor and a screening method that utilizes women's physiological phenomena, it is expected that cervical cancer diagnosis will be possible more simply and easily.
Even for those who are financially well-off, there are many inconveniences such as time burden and other inconveniences in getting a cervical cancer screening once a month. However, it becomes possible for women to have a natural check-up using the physiological bleeding that occurs naturally once a month, it is expected to be helpful to everyone beyond economic gap.
Our synthetic biology research can contribute to ending discrimination against poverty and achieving health equity, which is part of the Sustainable Development Goals (SDGs)
Reference
[1] National Cancer Institute, “Cervical Cancer—Patient Version,” *National Cancer Institute*, Jun. 15, 2023. https://www.cancer.gov/types/cervical
[2] R. Hull *et al.*, “Cervical cancer in low and middle‑income countries (Review),” *Oncology Letters*, vol. 20, no. 3, pp. 2058–2074, Jun. 2020, doi: https://doi.org/10.3892/ol.2020.11754.
[3] “Cancer Research and Treatment,”*www.e-crt.org*. https://www.e-crt.org/m/journal/view.php?number=3369 (accessed Oct. 08, 2023).
[4] R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2019,” *CA: a Cancer Journal for Clinicians*, vol. 69, no. 1, pp. 7–34, Jan. 2019, doi: https://doi.org/10.3322/caac.21551.
[5] World Health Organization, “Cervical Cancer,” *World Health Organization*, Feb. 22, 2022. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
[6] “World.” Available: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
[7] M. Arbyn *et al.*, “Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis,” *The Lancet Global Health*, vol. 8, no. 2, Dec. 2019, doi: https://doi.org/10.1016/s2214-109x(19)30482-6.
[8] National Cancer Institute, “Cervical Cancer Screening - NCI,” *www.cancer.gov*, Oct. 13, 2022. https://www.cancer.gov/types/cervical/screening
[9] “Dynamiker Cryptococcal Antigen Lateral Flow Assay (LFA).” Accessed: Oct. 08, 2023. [Online]. Available: https://www.rafer.es/sites/default/files/pack_insert-dnk-cryptococcal_antigen_lfa.pdf
[10] • MDGs Vs SDGs: 17 Differences - Public Health Notes,” *www.google.co.kr*. https://images.app.goo.gl/gJzX823NwP7TUkKL6 (accessed Oct. 08, 2023).