The rapid advancement of medical technology has made gene detection an essential tool for diagnosing and treating gynecological tumors. In 2025, the China Anti-Cancer Association successively released three expert consensus documents: the "China Expert Consensus on Normalized Selection of Cervical Cancer Gene Detection ^[1]," the "China Expert Consensus on Normalized Selection of Ovarian Cancer Gene Detection ^[2]," and the "China Expert Consensus on Normalized Selection of Endometrial Cancer Gene Detection ^[3]." These documents provided a crucial foundation for clinical practice.

The issuance of these expert consensuses signifies a new milestone in the development of gene detection for gynecological tumors in China. It represents a significant shift from "empirical medicine" to "precision medicine." The widespread adoption of gene detection technology allows doctors to gain a profound understanding of the genetic traits of tumors in patients, enabling them to tailor more precise and effective treatment plans. This not only substantially enhances treatment outcomes but also greatly diminishes unnecessary side effects of treatment, offering patients increased hope for survival. Moreover, gene detection significantly supports the prevention, early screening, and prognostic evaluation of gynecological tumors, effectively advancing the goal of comprehensive management of these conditions.

Gene testing: A Revolution from "One Size Fits All" to "Individualized" Treatment

Traditional tumor treatment primarily relies on pathological type and staging. However, patients at the same stage may respond differently to treatment and have varying prognoses. Gene testing uncovers the reasons behind these differences by analyzing the molecular characteristics of tumors, making "individualized precision medicine" a reality. For instance, in the case of ovarian cancer, the status of BRCA gene mutations and homologous recombination repair defects (HRD) can guide the use of PARP inhibitors, significantly extending patient survival ^[2].

Cervical Cancer: Management from HPV Screening to Targeted Therapy

1. Screening and shunting: Beyond HPV-DNA Testing

The primary risk factor for cervical cancer is a persistent infection with high-risk human papillomavirus (HPV). The consensus indicates that the HPV-DNA test is the preferred method for screening healthy individuals for cervical cancer. However, it cannot differentiate between transient and persistent infections, potentially resulting in overdiagnosis and overtreatment ^[1]. Consequently, the consensus suggests:

HPV E6/E7 mRNA Detection: This method directly reflects the activity of the viral oncogene and is superior to HPV-DNA detection in terms of both sensitivity and specificity for the diagnosis of cervical lesions ^[4].

DNA Methylation Detection: By assessing the methylation levels of genes such as PAX1 and FAM19A4, it is possible to identify precancerous lesions and early-stage cervical cancer, thereby reducing the need for unnecessary colposcopy examinations^[5].

2. Genetic Syndrome and Rare Types

Approximately 15%–30% of patients with Peutz-Jeghers syndrome (PJS) develop cervical gastric adenocarcinoma (G-EAC) unrelated to HPV infection. The consensus recommends that patients with PJS undergo testing for the STK11 gene, and that gynecological ultrasounds and cytology examinations be conducted regularly ^[6].

3. Precision Treatment for Advanced Patients

The consensus recommends the detection of the following biomarkers for advanced or relapsed metastatic cervical cancer:

Immunotherapy-related: PD-L1, mismatch repair defect (dMMR)/high microsatellite instability (MSI-H), tumor mutation burden (TMB);

Related to targeted therapy: gene fusion of HER2, RET, and NTRK ^[7].

For instance, Trastuzumab Deruxtecan has an objective response rate (ORR) of 50% for HER2-positive cervical cancer ^[8], and Selpercatinib is effective for RET fusion tumors ^[9].

Ovarian Cancer: HRD Detection Initiates the PARP Inhibitor Era

1. BRCA and HRD: The "Compass" of PARP Inhibitors

Homologous recombination repair defect (HRD) is present in approximately 50% of ovarian cancers. It is generally recommended that all patients with non-mucinous epithelial ovarian cancer undergo BRCA1/2 gene testing. HRD testing is then conducted on patients who test negative for BRCA to evaluate their suitability for PARP inhibitors ^[10]. Research has indicated that progression-free survival (PFS) is significantly extended in HRD-positive patients who continue treatment with PARP inhibitors ^[11].

2. Other Key Biomarkers

DMMR/MSI-H and TMB: These biomarkers guide the use of immunocheckpoint inhibitors such as Pembrolizumab.

HER2 vs. FRα: Trastuzumab Deruxtecan and somatuximab present new treatment options for patients with high expression of HER2 or FRα ^[12].

NTRK, RET, and BRAF: Rare mutations can be targeted with drugs like Lorlatinib and Selpercatinib ^[13].

Endometrial Carcinoma: Molecular Typing and Remodeling Patterns of Diagnosis and Treatment

1. Molecular Typing: A "Navigator" for Prognosis and Treatment

Based on TCGA research, endometrial carcinoma can be categorized into four types: the POLE hypermutation type, which has the best prognosis and is sensitive to immunotherapy; the MSI-H/MMR type D, which responds efficiently to immunotherapy with an ORR of 48% for PD-1 inhibitors ^[14]; the NSMP type, associated with a good prognosis and sensitivity to endocrine therapy; and the P53 mutation type, which has the worst prognosis and requires intensive treatment ^[15]. Molecular typing was first incorporated into the FIGO staging in 2023. For instance, patients with POLE mutations may have their staging downgraded to prevent overtreatment ^[16].

2. Lynch Syndrome Screening

Approximately 2%–5% of endometrial cancers are linked to Lynch syndrome. The consensus suggests screening the genetically susceptible population using immunohistochemistry (IHC) for MMR proteins, combined with MLH1 methylation analysis and MSI testing ^[17].

3. Rare Mutations and Targeting Opportunities

Mutations in the PI3K/AKT pathway (such as PTEN and PIK3CA) indicate potential efficacy for PI3K inhibitors; the absence of ARID1A is associated with chemotherapy resistance; and CTNNB1 mutations increase the risk of relapse in early-stage patients ^[18].

Challenges and Perspectives

Despite the significant value of genetic detection, its application still faces challenges:

(1) Insufficient detection rate: The homologous recombination deficiency (HRD) detection rate for ovarian cancer is only 30%, and there is an urgent need to improve patient awareness ^[19].

(2) Technical standardization: Different detection methods, such as immunohistochemistry (IHC), next-generation sequencing (NGS), and polymerase chain reaction (PCR), require further standardization.

(3) Cost and accessibility: Coverage for genetic testing by Medicare still needs to be improved.

(4) Data interpretation and clinical application: Interpretation of genetic test results should be combined with clinical and pathological characteristics to avoid overinterpretation or misunderstanding.

(5) Multidisciplinary collaboration: Multidisciplinary teams, including gynecologic oncology, pathology, and genetic counseling, need to strengthen communication and formulate individualized plans.

(6) Ethics and privacy: Genetic data involves patients' privacy, and a strict data protection mechanism should be established to prevent unauthorized access.

In the future, with the development of liquid biopsy, multi-omics integration, and artificial intelligence, genetic detection will guide clinical decisions more accurately and conveniently.

Genetic detection has become the cornerstone of gynecological tumor precision medicine. From screening and triaging for cervical cancer, to PARP inhibitor selection for ovarian cancer, and then to molecular typing of endometrial cancer, genetic information is gradually rewriting the diagnosis and treatment paradigm. Both doctors and patients should enhance their awareness of genetic testing, so that more patients can benefit from "individualized treatment" through multidisciplinary cooperation.

References

[1] China Consensus of Experts on the Normalization of Screening for Cervical Cancer Genes Based on Clinical Needs (2025 edition) [J]. Journal of Oncology, 2025 (No.7).

[2] China Expert Consensus on the Normalization of Gene Detection for Ovarian Cancer Based on Clinical Needs (2025 edition) [J]. Journal of Oncology, 2025 (No.9).

[3] China Experts Consensus on the Standardized Selection of Gene Detection for Endometrial Carcinoma Based on Clinical Needs (2025 edition) [J]. Journal of Oncology, 2025 (No.10).

[4] Malawi Med J. 2024 Jul 30; 36(2):120-127.

[5] BMC Cancer. 2024 Jul 29; 24(1):913.

[6] Acta Chir Belg. 2023 Aug; 123(4):448-453.

[7] Adv Ther. 2024 Nov; 41(11):4125-4139.

[8] Lancet Oncol. 2022 Oct; 23(10):1261-1273.

[9] J Clin Oncol. 2020 Apr 10; 38(11):1222-1245.

[10] Lancet Oncol. 2019 May; 20(5):636-648.

[11] J Clin Oncol. 2020 Jan 1; 38(1):1-10.

[12] N Engl J Med. 2023 Dec 7; 389(23):2162-2174.

[13] Lancet Oncol. 2020 Feb; 21(2):271-282.

[14] Sci Rep. 2025 Jan 20; 15(1):2497.

[15] Nature. 2013 May 2; 497(7447):67-73.

[16] Int J Gynaecol Obstet. 2023 Aug; 162(2):383-394.

[17] Zhonghua Fu Chan Ke Za Zhi. 2023 Oct 25; 58(10):755-765.

[18] Mod Pathol. 2017 Jul; 30(7):1032-1041.

[19] White Paper on the Status of Diagnosis and Treatment of Ovarian Cancer in China [J]. China Journal of Practical Gynecology and Obstetrics, 2023 (No.12).