Application case value and results of methylation in the diagnosis and treatment of cervical cancer

On October 28, the academic seminar on "Application Research of Methylation in Diagnosis and Treatment of Gynecological Tumors" (Phase II) jointly organized by China Maternal and Child Health Hospital and Juhe Bio was successfully held online. As an important part of the project promotion, this meeting brought together many well-known experts in the field of gynecology to discuss the practice and typical cases of methylation technology in clinical application.

The meeting was chaired and hosted by Professor Li Lei of Peking Union Medical College, Chinese Academy of Medical Sciences and Professor Han Lili of Xinjiang Autonomous Region People's Hospital. Professor Di Wen, leader of the methylation project and Renji Hospital affiliated to Shanghai Jiaotong University, gave an opening speech. Ms. Liu Yanling of China Maternal and Child Health Association, Professor Chen Qionghua of the First Affiliated Hospital of Xiamen University, Professor Chen Gang of the First Affiliated Hospital of University of Science and Technology of China, Professor Zeng Fei of Xiangya Third Hospital of Central South University, Professor Liang Hui of Xuzhou Maternal and Child Health Hospital, Professor Liu Dantong of Cangzhou Central Hospital, Hebei, Professor Xia Weiyu of Yueyang Central Hospital, Professor Zhang Ping of the Second Hospital of Shandong University, Professor Wang Xiaojing of Zhejiang Provincial People's Hospital and Professor Wu Zhe of Yueyang Central Hospital were invited to share and discuss in depth the typical cases of methylation application. The conference attracted hundreds of viewers to watch online.

Case 1: The value of methylation technology in detecting occult lesions in postmenopausal women

The patient was a 59-year-old woman who was found to be HPV16 positive in another hospital. One week later, she was treated for lumbar distension. Ultrasound showed enlarged uterus, multiple nodules, and uterine effusion after menopause. The squamous-columnar junction was not visible under colposcopy, and thin acetowhite epithelium was visible in the type III transformation zone. The iodine test was partially unstained, and the diagnosis was LSIL. Cervical scraping pathology suggested chronic inflammation; the pathology was CINⅠ. Considering the occult lesions in the type III transformation zone of menopausal women, the patient was tested for PAX1/JAM3 double gene methylation, and the result was positive, indicating a high risk of lesions. After cone resection, the pathology was upgraded to CIN3, involving the glands, and laparoscopic hysterectomy was performed.

This case demonstrates that PAX1/JAM3 dual gene methylation testing can help reduce the risk of missed detection of occult lesions in postmenopausal women due to decreased hormone levels. For biopsy showing chronic inflammation/low-grade lesions, positive methylation indicates that the lesions may be at risk of upgrading.

Case 2: Diagnostic role of methylation detection in cervical adenocarcinoma

In January 2020, the patient was tested for HPV16 positive and TCT abnormal in an external hospital due to "leucorrhea with blood streaks". After examination, LEEP was performed, and pathological consultation was diagnosed with invasive squamous cell carcinoma, combined with HSIL and adenocarcinoma in situ. Radical cervical resection was performed for fertility consideration; HPV16 was intermittently positive and recurrent during follow-up three years after surgery. Gynecological examination revealed vegetation at the cervical ostium, and pathology was normal; in March 2024, HPV16 was positive, but TCT, tumor markers and colposcopy were normal. Methylation technology was used for accurate auxiliary diagnosis of the lesion. The results showed that the PAX1/JAM3 double gene methylation test was double positive, and the colposcopy biopsy was invasive adenocarcinoma of the cervix. Afterwards, total hysterectomy was performed, chemotherapy and subsequent follow-up observation process were performed.

Cervical adenocarcinoma in situ is a lesion that may not be easily detected in the early stage, because there is no obvious acetowhite change under colposcopy, which increases the possibility of clinical misdiagnosis. PAX1/JAM3 dual gene methylation detection can provide more accurate risk assessment, make up for the deficiencies of missed diagnosis by traditional methods, and thus conduct further diagnosis and treatment in a timely manner.

Case 3: Clinical case of atypical lobular cervical glandular hyperplasia

The patient was 44 years old and was admitted to the hospital due to "coughing and urinary incontinence for 2 years and vaginal discharge for 2 weeks". The physical examination was normal, and the blood routine, coagulation function, thyroid function and tumor marker tests were all normal. The cervical cancer PAX1/JAM3 double gene methylation test results were positive. Hysteroscopic cervical tumor electroresection, endocervical canal scraping and endometrial biopsy were performed. Pathological examination showed lobular cervical glandular hyperplasia with regional atypical hyperplasia, and cervical micro-deviation adenocarcinoma was not excluded. One week later, laparoscopic extensive hysterectomy and left adnexectomy were performed under the assistance of the da Vinci robot. The pathological diagnosis showed lobular cervical glandular hyperplasia with focal atypical hyperplasia, accompanied by tunnel-like glandular clusters (type A), and no residual lesions were found in the left and right vaginal wall stumps.

Atypical lobular cervical glandular hyperplasia is a precursor lesion package of gastric adenocarcinoma (G-EAC). G-EAC is not related to high-risk HPV infection, and its clinical manifestations are extremely atypical. The hidden lesions make it difficult to obtain samples, and the screening and biopsy positive rates are low. The pathological morphological characteristics are similar to benign lesions, but the biological characteristics are highly malignant, which brings great challenges to diagnosis. The preoperative diagnosis rate is low and it is easy to be missed or misdiagnosed (up to 34%). This case fully demonstrates the application value of methylation detection technology in non-HPV-related adenocarcinoma/precancerous lesions.

The case sharing experts spoke passionately and vividly, and the content was exciting and fascinating. In the exchange and discussion session, the experts not only shared their rich practical experience, but also brought a lot of practical knowledge. The experts combined the cases with their own clinical experience to discuss the difficulties and challenges of cervical cancer diagnosis and treatment, and conducted in-depth exchanges on the application value of methylation technology in the detection of hidden lesions in postmenopausal women, the protection of fertility in women of childbearing age, and the missed diagnosis of adenocarcinoma, providing valuable insights and inspiration for the participants.

About CISPOLY

Beijing Origin Poly Bio-tec Co., Ltd. is a technology company driven by innovative technology and focusing on health. CISPOLY is a pioneer in the field of early diagnosis of gynecological tumors. With exclusive technology and patented markers as the core, it has developed early diagnosis products for gynecological tumors such as cervical cancer, endometrial cancer, and ovarian cancer, filling the gap in this field.

As women pay more and more attention to their own health, the women's health market will have great potential. In addition to the gynecological tumor early screening and early diagnosis product line, CISPOLY will also establish more women's health-related product pipelines in the future to create a leading technology innovation company in the women's health market.