A Prospective, Open, Observational Clinical Study on Endometrial Cytology and Cervical Methylation Testing for Screening and Evaluating Fertility-Sparing Treatment in Endometrial Cancer

Endometrial cancer (EC) represents a significant public health concern for women globally, with nearly 200,000 new cases diagnosed each year. It ranks as the fourth most common gynecological malignancy threatening women's health, particularly prevalent among women in developed countries . In China, EC holds a prominent position in gynecological oncology, with studies indicating that its incidence rate is surpassed only by breast and cervical cancers . In recent years, the incidence of endometrial cancer has been steadily rising, particularly among perimenopausal and postmenopausal women, with a notable trend toward younger age groups .

According to traditional etiological classifications, endometrial cancer can be divided into two types: Type I, which is estrogen-dependent, typically affects younger women, is characterized by lower cellular and tissue atypia, and is generally associated with a better prognosis. In contrast, Type II is independent of estrogen exposure, often exhibits high levels of cellular and tissue atypia, affects older women, and is linked to poorer prognoses.The 2023 FIGO guidelines introduced a molecular classification system for endometrial cancer based on gene expression profiles. This system identifies four molecular subtypes: POLE-mutant, mismatch repair-deficient (dMMR), no specific molecular profile (NSMP), and p53-mutant (p53abn). These classifications have shown improved prognostic accuracy and have been incorporated into the 2023 FIGO staging criteria. As a common gynecological malignancy, recurrent or metastatic endometrial cancer has a poor prognosis, which underscores the critical importance of early detection and diagnosis.

1.2 Early Screening Methods for Endometrial Cancer The search for effective early screening methods for endometrial cancer has garnered increasing attention from researchers and clinicians globally, with a growing body of studies addressing this issue. Currently, the primary method for early diagnosis remains pathological examination through endometrial curettage, which is considered the clinical gold standard. However, curettage has several limitations, including procedural complexity, cost, risk of intrauterine bleeding, potential iatrogenic infection, and patient discomfort.In addition to curettage, imaging techniques such as transvaginal ultrasound (TVU) are widely used for clinical diagnosis. TVU is a non-invasive, safe, and convenient method. However, its diagnostic accuracy is often limited by the apparent thickness of the endometrium, which can be influenced by various factors such as individual uterine anatomy and the patient's menstrual cycle phase. Blood spectrometry can detect endometrial cancer at all stages and may assist in identifying atypical endometrial hyperplasia. Additionally, several potential biomarkers, such as microRNAs, have been discovered. However, blood tests generally have low specificity and sensitivity, making them prone to interference from other pathological factors, which limits their clinical application prospects.

1.3 Endometrial Cytology Examination A review of commonly used screening methods reveals that each has its limitations and cannot be considered an optimal or universally applicable approach. Consequently, there is a pressing need for a more efficient, cost-effective, and low-risk screening method for endometrial cancer.

Liquid-based endometrial cytology is an emerging minimally invasive screening technique. This method involves collecting endometrial cells and tissues from the uterus and its downstream anatomical structures. The samples are preserved and analyzed using either liquid-based cytology techniques or tissue smear methods to reach a pathological diagnosis. Compared to invasive procedures such as fractional curettage, liquid-based cytology offers advantages in the screening of endometrial cancer, including being minimally invasive, convenient, and low-risk. In some clinical guidelines, liquid-based endometrial cytology has been recommended as a preferred screening method for endometrial cancer.