17 General introduction Ovarian cancer Late-stage presentation and difficulty in distinguishing between benign and malignant ovarian masses Lung cancer Late-stage presentation and high false positive rates during lowdose CT screening of high-risk individuals Endometrial cancer Rising incidence and many unnecessary invasive procedures for women presenting with abnormal bleeding symptoms Figure 4: Clinical challenges of cancer types for which patient-friendly biomarker testing was evaluated in this thesis. Schematic illustration of the anatomical location and short description of clinical challenges of endometrial, ovarian, and lung cancer. Created with BioRender.com. 1.5.1 Endometrial cancer Endometrial cancer or uterine cancer is the most frequently diagnosed gynecological cancer in developed countries with a rising incidence worldwide, accounting for 417,000 new diagnoses and over 97,000 deaths in 2020 (75). This gynecological malignancy arises from the inner lining of the uterus, known as the endometrium, and typically occurs in postmenopausal women (76). Women with Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome, have an increased lifetime risk of endometrial cancer (77). Endometrial cancer comprises a heterogeneous range of subtypes with diverse histological and molecular features. The majority of endometrial cancers (~80%) are low-grade endometrioid with a generally good prognosis. The remaining high-grade tumors, including grade 3 endometrioid and non-endometrioid tumors (serous, clear cell, and mixed adenocarcinomas, and carcinosarcomas), have a poor prognosis due to their aggressive growth pattern and higher risk of metastasis (76). Endometrial cancer is diagnosed by invasive procedures, in which a pipelle biopsy is performed by a specialist when a thickened endometrium is observed (78). In some inconclusive cases, a hysteroscopy (i.e. visual examination of the inside of the uterus with a hysteroscope to obtain a tissue specimen) is required for a final diagnosis. Fortunately, endometrial cancer is often detected at an early-stage due to the presence of abnormal postmenopausal bleeding symptoms. Nevertheless, only a minority (~9%) of women experience these symptoms due to malignancy (79). The low specificity (~52%) of ultrasound measurements for endometrial thickness results in a substantial number of women without cancer undergoing unnecessary invasive clinical examinations to rule out malignancy (80). Moreover, women at increased risk for endometrial cancer, including women with Lynch syndrome, repeatedly undergo clinical examinations to rule 1
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