In the course of developing our project, we placed a strong emphasis on ensuring that our product and
work process are responsible and beneficial to the world, thereby adhering to our core values. This was
achieved by being open-minded and constantly refining our understanding, design, and actions by engaging
in constructive interviews with experts in the field—researchers, doctors, and stakeholders who
frequently challenged our ideas and guided us toward making our project safer, scientifically accurate,
and ethically sound.
1.Interview with Mr. Hao
On July 22, 2023, the YiYe-China iGEM team interviewed Director Sun Li and Director Hao Wei from
Kindstar Medical Laboratory Co., Ltd, a large-scale high-end medical specialty testing service
inspection group in China committed to leading the advancement of China s specialty testing technology
and services.
Figure1. Interview with Mr. Hao
First, YiYe inquired with the directors of Kindstar about the factors to be taken into account for the
establishment of laboratories. They noted that a laboratory s location is closely tied to the city s
economic and medical development, with easier resource acquisition in super first-tier cities. While
partnering with West China Hospital offers quicker and more easily accessible funding, moving to
second-tier or county cities signifies fewer resources for the company’s development.
Following that, YiYe inquired about Kindstar s level of expertise in projects related to miRNA and
lncRNA, which are currently prominent research topics. The directors shared their insights on the novel
assays utilizing these RNA molecules and their prospects. They emphasized the significance of early
screening, highlighting that detecting cancer at an early stage allows for timely treatment. They
explained that once cervical cancer has progressed to stages 1, 2, or 3, or has spread, the best time
for treatment has been missed. Therefore, effective prevention measures are crucial to greatly reduce
the possibility of a cervical cancer diagnosis in the future. In light of this knowledge, our team
decided to re-envision our experiment. Instead of relying on blood sample centrifugation to identify
circulating tumor cells as an indicator of cervical cancer, we recognized that a more effective approach
would be to directly obtain cervical cell samples through cervical scraping and then detect cancer cells
within these samples. This shift in approach is grounded in the understanding that, during the early
stages of cervical cancer, cancer cells are predominantly localized in the cervix itself. Therefore,
detecting cancer cells through cervical smears is essential, as relying on blood samples, which are
largely devoid of cancer cells in the early stages, might lead to missed diagnoses.
When delving into this technology, as the directors also mentioned, YiYe should consider two crucial
aspects. Firstly, the time taken to operate the whole process and the degree of convenience are very
important to the workers who will be using this technology. Hence, YiYe should focus on enhancing the
technology s timeliness, reducing detection times, improving accuracy, and transitioning from a
qualitative to a quantitative approach. Upon receiving their valuable advice, we thought of a more
convenient way for quantifying fluorescence values: by dropping a sample of cervical cells onto a test
strip and then using a fluorescence reader to quantitatively assess the fluorescence value. The
directors emphasized the significance of gaining a comprehensive understanding of clinical prerequisites
during the development of a clinical program. This guidance prompted us to proactively engage with
cervical cancer specialists such as Doctor Li, Doctor Guo, and Doctor Cai to deepen our knowledge in
this area. Secondly, it is imperative to consider the context in which the technology will be employed.
This context encompasses factors such as the applicable patient demographics, selection criteria,
disease stage, the clinical information provided by the test, and the monitoring of diagnosis and
treatment progress in clinical settings.
Finally, the directors from Kindstar gave us some advice for life science practitioners. There are two
main, promising directions that they would like students to consider in their future studies: drug
research or diagnostics. As an example, doing miRNA target research, including detection targets and
drug research targets. The molecular drugs or antibody drugs that are currently being developed are
aimed at drug targets. If the target in the drug can be blocked or eliminated, the development of the
drug is very successful. However, miRNAs are not only used for drugs or testing. If the technology is
advanced enough, therapeutic targets can be developed to differentiate between patients and normal
people.
Figure2. Director Hao leading YiYe-China iGEM team members on a Kindstar company tour
2. Interview with Dr. Li
At the end of July, our team was honored to interview Dr. Jane Li, an expert in cervical cancer, and
after we briefly introduced to Dr. Li our project on early screening of cervical cancer using MALAT1 in
combination with microRNA, we asked some questions.
First, Dr. Li explained to us that the causative factor of cervical cancer is the persistence of
high-risk HPV infection. Regarding the relationship between non-coding RNA expression and cancer, she
answered: “Currently, non-coding RNAs have been shown to be involved in a variety of cell signaling as
well as tumor immunity processes, and therefore are closely related to the development of
cancer/disease. At this stage, extensive basic research is actively exploring the connection between
non-coding RNAs and cancer. Numerous high-quality articles have already been published, illustrating the
potential utility of non-coding RNA expression in the early diagnosis of cervical cancer. In my personal
view, this holds significant clinical promise and prospects. However, it s crucial to acknowledge that
the transition from successful basic research outcomes to clinical applications often entails a lengthy
process. Therefore, a cautious yet hopeful approach is warranted as we monitor these developments.”
Dr. Li highlighted the benefits of non-coding RNA in early disease diagnosis, including the following
aspects:
（1）Specimen can be quickly collected from a wide range of sources, such as blood, urine, pleural fluid,
etc.
（2）Non-coding RNA exhibits strong stability, making it resilient even under adverse conditions like
high temperatures, extreme pH levels, and prolonged freezing.
（3） Detection is typically carried out using RT-qPCR, a well-established, time-efficient, and
cost-effective technology.
Nevertheless, non-coding RNAs come with certain limitations:
1. Specificity can be an issue with some non-coding RNAs. For example, heightened levels of miR-21 in
peripheral blood have been linked to many conditions such as prostate cancer, gastric cancer, lung
cancer, and even inflammation, thus it is hard to distinguish the specific condition of the patient.
2. The reproducibility of results can be low, leading to varying or even contradictory findings in
different studies involving the same non-coding RNA. This variance may be attributed to factors like
sample size, statistical techniques, and the specificity of the assay method employed.
Considering the limitations mentioned earlier, non-coding RNAs continue to encounter significant
challenges on their path to clinical translation. Since certain non-coding RNAs are superior to
traditional tumor markers in terms of adjuvant diagnosis and prognosis determination of tumors, a large
number of clinical trials targeting non-coding RNAs are underway. Non-coding RNAs will hopefully be used
in clinical practice if standard operating procedures for evaluating non-coding RNAs can be established,
including the selection of samples, RNA extraction, assaying, and standardization of methods.
Finally, we inquired with Dr Li about her outlook on the future of technology in cancer screening and
staging. She replied, “Cancer is a disease that seriously jeopardizes people s health. Not only do we
need to treat cancer, but also to screen and prevent it at an early stage. Currently, the screening
methods for cancer are limited, and there is a certain degree of under-diagnosis and misdiagnosis. As
clinicians, we hope that there are more sensitive, convenient, and less invasive ways to screen and
stage cancer. In the future, we should strengthen the basic scientific research of genomics,
transcriptomics, proteomics, and metabolomics in the field of cancer screening, accelerate the fusion of
traditional microepidemiology with biotics and imaging technologies, and systematically integrate the
key technologies of trace detection, hidden lesion detection and sensing, knowledge-based reasoning, and
multi-source heterogeneous data fusion, so as to build an accurate and early cancer screening system
suitable for the Chinese population.’
Figure3. YiYe China team members Mingxi Huang and Yumin Chiang interviewing Dr. Li
During this interview, we gained valuable insights into the potential of non-coding RNA in the realm of
tumor diagnosis. Nevertheless, it s important to recognize that, at its current stage, the detection and
clinical implementation of non-coding RNA still confront several technical challenges. For instance,
there are ongoing questions about how to precisely differentiate various RNA types in high-throughput
sequencing, how to achieve rapid, efficient, and cost-effective non-coding RNA detection, and how to
enhance sensitivity, specificity, and other critical detection metrics. We firmly believe that as
technology continues to advance, the utilization of exosomal non-coding RNA for early cervical cancer
diagnosis will become a tangible reality.
3. Interview with Dr. Guo Yulin
On July 25th, the YiYe-China iGEM team embarked on a visit to the Hubei Maternal and Child Health
Hospital, where we were pleased to engage in an enlightening conversation with Dr. Guo Yulin. Driven by
an unwavering passion for the field of medicine, Dr. Guo has dedicated seven years to her medical
profession. Her commitment to continuous growth and staying abreast of cutting-edge medical advancements
is evident through her active participation in hospital-organized training programs. Of particular
significance is her keen interest in staying updated on the latest cervical cancer detection
technologies available in China.
Figure4. YiYe China team members are interviewing Dr. Guo
The interview with her gave us the essential information that the incidence of cervical cancer in our
country has been showing an overall increasing trend. Furthermore, a noteworthy trend is the growing
proportion of cervical cancer cases among individuals under the age of 35. This information aligns with
the data from the World Health Organization (WHO), which indicated a rising number of young cervical
cancer patients in comparison to previous years.
Dr. Guo Yulin further highlighted the presence of pre-cancerous uterine cervical lesions, noting a
growing number of young patients seeking medical care for these conditions. She attributes this trend to
two primary factors: the earlier onset of sexual activity among women in China and the development and
prevalence of accurate screening techniques for the detection of pre-cancerous lesions.
Dr. Guo Yulin introduced us to the main cervical cancer screening methods currently employed in China,
known as the three-step diagnostic approach. This method consists of several stages:
Firstly, there is the HPV test or TCT, also known as the cytology test, which serves as the initial
screening process. If any anomalies arise during this primary screening, physicians may recommend a
colposcopy. If a suspected lesion is identified during the colposcopy, it is highly advisable for the
patient to undergo a biopsy, specifically the pathology test. The pathology test is the conclusive step
in diagnosing cervical cancer, as it adheres to precise diagnostic criteria.
In cases where cervical tissue lesions are confirmed, healthcare professionals can then determine the
appropriate follow-up treatments based on the degree of the lesion.
Dr. Guo Yulin also emphasized the relationship between the HPV test and colposcopy. While the HPV test,
when conducted with machines, boasts high sensitivity, it can overdiagnose women as cervical cancer
patients, potentially inflating the actual numbers. Notably, this may result in an increased number of
individuals referred to colposcopy, a procedure financially subsidized by the Chinese government.
Consequently, this puts pressure on both hospitals and the government, as the referral rate surges,
accompanied by a substantial economic burden on the government s healthcare system. Dr. Guo also shed
light on the limitations of using cytometry blood methods, which necessitate the expertise of
experienced pathologists for accurate interpretation. Notably, variations in doctors skills and
proficiency across different regions of China can lead to varying levels of sensitivity, potentially
resulting in an underestimation of the actual number of cervical cancer cases. Dr. Guo s recommendation
is to employ a combined approach utilizing both HPV testing and cytology for more dependable and
accurate screening results.
Figure5. Tingyu Zhang is interviewing Dr. Guo
Since the number of young women diagnosed with cervical cancer is increasing, we are concerned whether
these patients might lose the opportunity to become mothers due to cervical cancer treatment. In
response to this, Dr. Guo Yulin explained that the possibility of preserving fertility largely hinges on
the patient s overall health condition. For patients diagnosed with early-stage cervical cancer who
aspire to have children, the medical team endeavors to take every possible measure to conserve the
patient s uterus. However, in cases where a patient has undergone a complete hysterectomy, it is
impossible for her to have children.
Finally, Dr. Guo imparted valuable advice on real-life strategies for preventing cervical cancer. A
three-tiered prevention is vital. The first level of prevention centers on averting HPV infection,
cervical cancer, and precancerous lesions by ensuring individuals receive the recommended HPV vaccine
doses. Additionally, Dr. Guo stressed the importance of adopting responsible sexual habits. It is
crucial to refrain from engaging in sexual activities with multiple partners or those who have multiple
sexual partners, as HPV transmission occurs through sexual intercourse. Delaying sexual activity until
adulthood is also encouraged. Moreover, regular screening plays a critical role in this preventive
strategy. Regular check-ups enable doctors to detect precancerous lesions and cervical cancer promptly,
facilitating timely intervention and ultimately contributing to a reduction in the incidence and
mortality rates associated with cervical cancer. The final stage of cervical cancer prevention involves
tailored treatment. Doctors typically determine the most suitable treatment plan, be it surgery,
radiotherapy, or chemotherapy, based on a comprehensive clinical analysis of the patient s condition.
This interview shed light on the alarming prevalence and high mortality rates associated with cervical
cancer. Recent years have witnessed a surge in diagnoses among young girls, primarily attributed to
unhealthy sexual behaviors and early sexual initiationRecognizing the evident link between early
intervention and successful recovery from cervical cancer, we also identified a pressing need to address
the subjectivity inherent in TCT test results, which are often reliant on the expertise of individual
doctors. By developing technology that can mitigate this subjectivity, we envisaged a future where more
women could be safeguarded from this devastating disease.
4. Interview with Doctor Cai
According to the World Health Organization, cervical cancer is the fourth most common cancer among
women globally, making the early detection and effective screening of cervical cancer vital. In our
pursuit to contribute to the advancement of cervical cancer pre-screening, our team embarked on a
journey to learn from experts in the field.
On July 31, 2023, our YiYe China iGEM team visited Zhongnan Hospital of Wuhan University and had the
great honor of interviewing Professor Hongbing Cai, deputy director of Women s and Children s Hospital,
who provided us with valuable advice for our project.
Figure6. Mingxi Huang and Yumin Chiang are interviewing Professor Cai
In China, cervical cancer is the most common gynecological tumor with the highest incidence rate.
Professor Cai introduced to us the methods of early screening and diagnosis of cervical cancer. She
mentioned that currently, early screening mainly relies on two methods: HPV testing and TCT
(liquid-based cytology). Diagnosis is divided into three stages: first, cytological examination, then
the combination of cytological examination and HPV testing, and if the results are abnormal, a vaginal
colposcopy examination is performed. If problems persist after the colposcopy examination, a biopsy is
performed to confirm the diagnosis. This constitutes a three-tiered diagnostic approach.
Professor Cai informed us that the causes of cervical cancer are very diverse, but one of the most
definite causes is HPV infection. As mentioned earlier, HPV testing is an early diagnostic method, with
nearly 95% or more of cervical cancer patients testing positive, especially for HPV16 and HPV18, which
have the highest positivity rates. HPV16 is mainly associated with cervical squamous cell carcinoma,
while HPV18 is mainly related to cervical adenocarcinoma.
Furthermore, the occurrence of cervical cancer is also related to other factors such as environmental
factors, lifestyle habits, and diet. Among these, multiple births and having multiple sexual partners
have a clear correlation with the incidence of cervical cancer. Therefore, adopting a healthy lifestyle
is essential for preventing cervical cancer.
Professor Cai pointed out that the incidence of cervical cancer varies among populations from different
regions. Generally, areas with relatively poor economic conditions such as mountainous and rural areas,
tend to have poor personal hygiene and hence have higher rates of cervical cancer. Knowing this crucial
information, our team paid more attention to the menstrual hygiene of women in impoverished areas.
We discovered that girls in Dawu County, Hubei, faced menstrual poverty and could only afford
low-quality sanitary pads. In reaction, we donated 1200 sanitary pads to the female students in the
mountainous region of Dawu to improve their hygiene conditions and help them in the early prevention of
cervical cancer and other women s health issues.
Figure7. Girls from DaWu are receiving sanitary pads
Professor Cai advocates regular screening for women who engage in sexual activity before the age of 21.
Between the ages of 21 and 30, cytological examinations are recommended. After the age of 30, combined
monitoring of HPV and TCT is advised. Negative results over three consecutive years can extend the
screening intervals. Initially, two to three HPV and TCT tests should be conducted, followed by
screenings every three to five years. Regular screening is recommended before the age of 65, after which
it may no longer be necessary. In summary, regular screening is effective in early detection of cervical
cancer.
As Professor Cai indicates, the challenge in early diagnosis of cervical cancer primarily lies in
raising awareness. While early diagnosis of cervical cancer is not inherently complex due to its typical
symptoms, many individuals lack awareness of this type of cancer. Therefore, it is crucial to educate
more people about the symptoms of cervical cancer, such as post-coital bleeding, increased vaginal
discharge, and bleeding after bowel movements, so that individuals seek medical attention promptly upon
experiencing such symptoms.
Upon realizing this issue, our team took proactive steps to promote knowledge about cervical cancer.
For instance, we published articles on early screening and treatment methods for cervical cancer on our
WeChat official account. We also set up stands in ShiLiuHong Village to educate local residents about
cervical cancer, distributing pamphlets, particularly targeting elderly women, who have the highest
mortality rates from cervical cancer. We emphasized the importance of cervical cancer screening.
Additionally, we introduced cervical cancer and our project in schools across nine cities, including
Wuhan, Beijing, Tianjin, Shenzhen, Guangzhou, Nanjing, Chengdu, Boston, and Versoix, to raise awareness
about cervical cancer prevention and early screening.
Figure8. YiYe China iGEM Wechat Official Account articles: "Scientific Knowledge Popularizing: The
Treatment of Cervical Cancer " (left) and "Idea Battle: Using Long Noncoding RNA in the Early Screening
of Cervical Cancer"
Regarding the "sensor" our team developed that utilizes the fluorescence intensity changes in miRNA and
lncRNA interactions for cervical cancer screening, Professor Cai believes that while our "sensor" holds
potential in cervical cancer research, there are critical factors to consider when applying it to
cervical cancer screening.
Firstly, our "sensor" is invasive, whereas current cervical cancer screening methods are typically
non-invasive. Cervical cytology, a common non-invasive screening method, involves collecting cervical
cell samples and observing cell changes for preliminary screening. If abnormal cells are detected, a
cervical biopsy can be performed for confirmation. Therefore, it is essential to address how to
transform our technology into a non-invasive screening method.
Secondly, cervical cancer is usually diagnosed through cytology and pathology, with pathology being the
gold standard. The cervix is a relatively accessible location for biopsy samples. Cytological screening
is non-invasive, involving the collection of cell samples from the cervix to detect cell changes. If
there are suspicious findings, a cervical biopsy can be conducted. The key indicator for diagnosing
cervical cancer is whether cancer has breached the basement membrane. Consequently, our technology may
face challenges in early diagnosis.
Moreover, miRNA and lncRNA research is typically used for studying mechanisms of metastasis or drug
targets in late-stage patients. In early diagnosis, these biomarkers may be influenced by various
uncertain factors within the complex human body. Therefore, utilizing miRNA or lncRNA for early cervical
cancer diagnosis may have certain limitations. However, our technology may hold potential value in
predicting cervical cancer treatment outcomes.
In summary, Professor Cai emphasizes that careful consideration is needed when applying our technology
to cervical cancer screening, as there may be challenges to overcome. However, our technology holds
significant potential for predicting cervical cancer treatment outcomes.
Professor Cai acknowledged the importance of pre-screening and early diagnosis in cervical cancer
treatment.
Firstly, screening aims to identify individuals at high risk of cervical cancer from the general
population for appropriate interventions and treatment. The goal of screening is to detect potential
precancerous lesions early because cervical cancer typically has a long precancerous stage that can last
for ten to twenty years. Early screening allows for the timely detection of these precancerous lesions
and the implementation of interventions such as cone biopsy or hysterectomy to halt the progression of
lesions, thereby reducing the incidence and mortality rates of cervical cancer.
Secondly, early diagnosis is equally critical for cervical cancer control. If patients can be diagnosed
in the early stages of cancer development, treatment outcomes are generally more favorable. For
instance, early-stage cervical cancer (Stage IA) typically only affects a small portion of the cervix,
making surgical treatment relatively simple and highly curative. Early diagnosis allows for the
identification of these patients and timely surgical treatment, achieving a five-year survival rate of
over 95%.
Moreover, even in advanced stages of cervical cancer, drug therapy can to some extent control the
disease and improve the patient s quality of life.
In summary, screening and early diagnosis are essential tools for lowering the incidence and mortality
rates of cervical cancer. Through public education and increased screening rates, we can better prevent
and manage this disease, enabling patients to receive timely treatment and improve their survival rates.
Professor Cai notes that although our project does not currently involve clinical practice, there is
significant potential and room for exploration from a research perspective. Laboratory research serves
as a solid starting point, involving the cultivation and study of cells, as well as the observation of
tissue slices. However, this requires a sound understanding of background knowledge, especially in areas
related to miRNA, among others. Therefore, our iGEM team acquired foundational knowledge in genetics and
genetic engineering before conducting experiments and gained insights into the characteristics and
functions of mRNA and lncRNA. Professor Cai highlights the importance of collaboration with medical
professionals who have extensive clinical experience and can provide valuable guidance. Following her
advice, we sought guidance from Dr. Guo Yulin at the Hubei Provincial Maternal and Child Health
Hospital.
Professor Cai points out that the diagnosis of cervical cancer, whether in its early or late stages,
still heavily relies on imaging within the field of pathology. Imaging can determine the location and
stage of the tumor. Therefore, without pathological support, it is challenging to make qualitative
assessments. The study of miRNA might offer the potential for predicting treatment outcomes earlier,
even though this method may face scrutiny. To conclude, cervical cancer screening and staging are
complex and diverse fields that require the integration of various approaches and specialized knowledge
to make advancements.
