Role of Biomarkers in Diagnosis of Cervical Cancer

Abstract: Cervical cancer (CC) is a malignant tumor of the female genital tract, and mainly induced by HPV infection(especially HPV16 and 18). Squamous cell carcinoma is the most common one. CC is considered to be a sexually transmitted disease, since the key cause of disease development is persistent infection of HR-HPV. Early symptoms are not obvious. During the development, vaginal bleeding and abnormal discharge can appear. The key prevention is regular gynecologic examination and HPV detection. After diagnosis, various treatment methods can be used, like surgical operation, radiotherapy and chemotherapy etc. There has been a decline in the average age of cervical cancer around the world. The younger trend receives a lot of attentions. In the developing countries, the mortality rate of cervical cancer is still up to 87%. Thus, it’s necessary to discover new biomarkers to better forecast the development of cervical cancer.

Keywords: Cervical Cancer Markers, Tumor Markers, Cancer Treatment and Prevention, Cancer Research

1. Common Cervical Cancer Markers

1.1. SCC-Ag

Squamous cell carcinoma - antigen(SCC-Ag) is the important marker for cervical squamous cell carcinoma. The normal reference value is 1.5 ng/mL. For diagnosed patients, 67% - 100% of them have the higher SCC-Ag. The increase of recurrent patients is usually 3-9 months earlier than other symptoms. Thus, SCC-Ag is applied in the new and recurrent diagnosis, and also the important marker of efficacy and disease surveillance. Researches show the recurrence rate for patients with 4 ng/mL SCC-Ag above is higher than those blow 4 ng/mL. Besides, the level of SCC-Ag is related to prognosis. The disease-free survival period for patients with lower level SCC-Ag is better than high level patients.

1.2. CA125

CA125 is closely related to epithelial ovarian carcinoma, but may increase in cervical cancer and endometrial cancer. Such as, CA125 level of 60% - 80% cervical adenocarcinoma patients can increase. The normal reference value is 35 U/mL. The increase is usually 3-6 months earlier than clinical tumor examination, and related to size and quantity of the tumor. Thus, cervical adenocarcinoma and cervical squamous cell carcinoma patients(normal SCC-Ag) with increased CA125 are suggested to use CA125 as the tumor marker for early screening and recurrence prediction.

1.3. CEA

Carcinoembryonic antigen(CEA) is first found in fetal and colon cancer tissue. It also exists in various adenocarcinomas and considered to be a broad-spectrum tumor marker. As one of the adenocarcinomas, cervical adenocarcinoma is the great increased CEA level of mucinous adenocarcinoma patients. The normal reference value is 5 μg/L. The increase level is related to the number of cancer cells. Researches show the positive rate of CEA in cervical adenocarcinoma patients is up to 92.6%. Although early screening is unsuitable, CEA can be used with CA125 and CA19-9 to help diagnosis and treatment of cervical adenocarcinoma.

1.4. CA19-9

The normal reference value of CA19-9 is 37 U/mL. CA19-9 is mainly distributed in digestive tract epithelium, and usually related to gastrointestinal cancer. The sensitivity and specificity of CA19-9 in cervical cancer is lower, but it can help diagnosis. Researches show the later-stage cervical cancer has larger tumor diameter, lower differentiation and higher level of CA19-9. Besides, the positive rate in adenocarcinomas is higher than squamous carcinomas. The CA19-9 level rapidly decreases in postoperative and chemotherapeutic cervical cancer patients, and can efficiently reflect therapeutic effect.

2. Cervical Cancer Associated Tumor Markers

2.1. HE4

Cervical cancer is highly expressed by HE4. HE4 is related to depth of myometrial invasion and retroperitoneal lymph node metastasis. Thus, HE4 can be used as the high risk factor. During the diagnosis and treatment, detection of HE4 level can help doctors evaluate patients’ severity of the disease and prognosis. The increase of HE4 level may show the great severity of cervical cancer. More active treatment and surveillance are required.

2.2. HIF-1 and VEGF

Tumor hypoxia is the key factor of solid tumor development(e.g. tumors in prostate, cervico, breast, brain and neck etc ) and treatment of drug-resistance. Due to the limitation of invasive detection technologies, researchers start to use endogenous markers related to tumor hypoxia, e.g. level of HIF-1, VEGF and hemoglobin etc. HIF-1 is stable during hypoxia, and binds with HIF-β to form dimer and regulate related genes adapting to oxygen depletion. Researches show the increase of HIF-1α and VEGF level is relevant to adverse reaction of radiotherapy for cervical cancer. The expression change of preoperative chemotherapy can forecast therapeutic sensitivity of patients.

3. Role of Tumor Markers in Diagnosis of Cervical Cancer

Tumor markers can help diagnosis of cervical cancer. The accurate diagnosis depends on clinical symptoms, gynecologic examination, cytological examination and imaging examination. Clinical symptoms like vaginal bleeding and increased discharge require for timely treatment. Experienced doctors will evaluate features of cervical lump. Cytological examination(e.g. TCT and HPV detection ) is the important screening method, and can find precancerous lesion and cancer cells. Imaging examinations include CT and ultrasonic. Colposcopy examination can observe suspicious lesions and conduct biopsy.

4. Recommended Products

REFERENCES

[1]NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer, PMID: 38970106.
[2]Machine learning-based radiomics for predicting outcomes in cervical cancer patients undergoing concurrent chemoradiotherapy, PMID: 38801795.