Cervical cancer is the most commonly diagnosed cancer worldwide and the most common cancer in females living with human immunodeficiency virus (HIV). Cervical cancer is classified as an acquired immune deficiency syndrome-defining disease. Brain metastases (BMs) from cervical cancer are extremely rare, with an incidence rate of approximately 0.63%, and there is limited information on optimal treatment protocols and patient outcomes. Since brain lesions are sequestered behind the blood-brain barrier, multimodal treatment approaches are crucial to help improve the prognosis of cervical cancer in patients with BMs who are also living with HIV.

A 42-year-old Chinese female with HIV infection was diagnosed with stage IIIC1r cervical cancer in March 2022 based on the International Federation of Gynecology and Obstetrics system. Fourteen months after undergoing the initial treatment with concurrent chemotherapy and radiotherapy in January 2024, the patient presented to a local hospital with a severe explosive headache. The patient underwent craniotomy and postoperative pathological examination confirmed metastasis of cervical squamous cell carcinoma to the brain on February 1, 2024. Following surgery, the patient received external beam radiotherapy for the metastatic lesions. The patient has been under observation for 7 months with no evidence of tumor recurrence.

Females living with HIV are more than three times more likely to be diagnosed with cervical cancer. Due to the scarcity of cervical cancer BMs, therapeutic protocol experience is limited. In addition to the existence of the blood-brain barrier, the treatment of cervical cancer BMs appears to be exceptionally complex, and a multi-modal treatment approach consisting of chemotherapy, surgery, and radiation may help prolong patients’ life. For females living with HIV, antiretroviral therapy should be prioritized, as recommended by the Center for Disease Control in China. An intact immune system and a high CD4⁺ count are positive indicators of treatment response and tumor reduction. The overall survival of patients with cervical cancer after brain metastasis is approximately 3-5 months. However, owing to multimodal therapy and the use of antiretroviral therapy, the patient reported in this case showed no signs of recurrence after prolonged follow-up.

• Brain metastasis
• Cervical cancer
• Antiretroviral therapy
• Multi-modal treatment
• Case report

• CNS metastasis
• Uterine cervix tumour
• brain metastasis
• squamocellular carcinoma
• systematic review

• Metastatic cervical carcinoma
• Neuro oncology
• Neuropathology

• Adenocarcinoma
• Brain
• CNS
• Cancer
• Cervical
• Craniotomy
• Endometrium
• Gamma knife
• Gynecological
• Intervention
• Leiomyosarcoma
• Lesions
• Metastasis
• Neurosurgery
• Squamous cell carcinoma
• Survival
• Uterine

• Female
• Humans
• Middle Aged
• Brain Neoplasms/secondary
• Brain Neoplasms/surgery
• Brain Neoplasms/therapy
• Radiosurgery/methods
• Retrospective Studies
• Survival Analysis
• Treatment Outcome
• Uterine Neoplasms

• brain metastasis
• cervical cancer
• hpv
• multi-organ
• squamous cell carcinoma

• Brain metastasis
• Gynecology oncology
• Neurologic symptoms

• Brain metastasis
• Cervical cancer
• Prognostic factors
• Survival

• Brain Neoplasms
• Female
• Humans
• Prognosis
• Retrospective Studies
• Survival Analysis
• Uterine Cervical Neoplasms

• Brain, Uterine Cervical Neoplasms
• Neoplasm Metastasis
• Risk Factors

Cervical carcinoma is one of the serious pernicious cancers that influence women's health. Invasion and metastasis are the chief reason of poor prognosis of cervical carcinoma. Hypoxia-inducible factor-1α (HIF-1α) is a significant regulatory factor of intracellular oxygen supersession, and its expression or increased activity is closely related to the arise and expansion of various human tumors. However, the relationship between HIF-1α (hypoxia-inducible factor 1) and Hippo pathway target gene Yes-related protein (YAP) and transcriptional coactivator (TAZ) in cervical carcinoma remains unclear. Here, we studied the clinical correlation of HIF-1α and YAP/TAZ expression in normal tissues, cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (CSCC). In order to analyze the role of HIF-1α in CCSC in vitro, SiHa cells with high expression of HIF-1α and C33a cells with low expression of HIF-1α were screened by detection. After transfection with lentivirus, HIF-1α levels were downregulated in SiHa cells and upregulated in C33a Cells, respectively. Then, the expression of HIF-1α in transfected cervical cancer cells Siha and C33a was detected by qRT-PCR and Western blot, and the expression of YAP/TAZ was detected in cervical squamous cell carcinoma cells after HIF-1α expression was altered. To explore HIF-1α role in cell proliferation, invasion, and metastasis, we examined the changes of cell function in cervical cancer cells with HIF-1α overexpression and inhibition by MTT assay, wound healing assay, Transwell test, and other cell function tests. At the same time, HIF-1α overexpression and HIF-1α inhibition cervical cancer cells were transplanted into nude mice, and tumors were isolated from the nude mice, and tumor volume and weight were observed. In conclusion, HIF-1α significantly promotes the proliferation, invasion, and migration of cervical carcinoma cells by upregulating YAP/TAZ. In addition, YAP/TAZ, the target gene of Hippo pathway, plays an important role in CCSC cells, pointing out that HIF-1α is provided with treatment potential for the treatment of CCSC.

Tumor-derived exosomes (TDEs) are actively produced and released by tumor cells and carry messages from tumor cells to healthy cells or abnormal cells, and they participate in tumor metastasis. In this review, we explore the underlying mechanism of action of TDEs in tumor metastasis. TDEs transport tumor-derived proteins and non-coding RNA to tumor cells and promote migration. Transport to normal cells, such as vascular endothelial cells and immune cells, promotes angiogenesis, inhibits immune cell activation, and improves chances of tumor implantation. Thus, TDEs contribute to tumor metastasis. We summarize the function of TDEs and their components in tumor metastasis and illuminate shortcomings for advancing research on TDEs in tumor metastasis.

• angiogenesis
• immunosuppression
• metastasis
• pre-metastatic niche
• tumor-derived exosomes

• carcinomatous meningitis
• cerebrospinal fluid cytology
• cervical cancer
• leptomeningeal metastasis
• magnetic resonance imaging

Cervical cancer is caused by a persistent infection with high-risk types of Papillomaviruses (hrHPV); HPV16 and HPV18 are associated with about 70% of the cases. In the last decades the introduction of a cervical cancer screening has allowed a decrease in cervical cancer incidence and mortality; regular adhesion to the screening procedures, by pap test or HPV test, and colposcopy, according to the international guidelines, prevents cancer development and allows for diagnosis at the early stages. Nowadays, in industrialized countries, it is not common to diagnose this pathology in advanced stages, and this occurrence is frequently associated with patient’s unattendance of cervical screening programs. We describe a case of delayed diagnosis of cervical cancer, posed only after the onset of the neurological symptoms caused by leptomeningeal metastases, despite a two-year history of abnormal cytology. The endocervical mass was analyzed by immunohistochemistry, and search and typing of HPV sequences was performed by PCR in the meningeal carcinomatous cells. A poorly differentiated squamous cell carcinoma was diagnosed, and HPV18 sequences were detected. This rapidly fatal case highlights the importance of following the evidence-based recommended protocols and the preventive role of the population-based cervical cancer screening programs.

• HPV18
• cervical cancer screening
• cervical carcinoma
• leptomeningeal carcinomatosis

This review investigated the prevalence, clinical characteristics, clinical presentation, diagnosis, treatment, and prognosis of patients with brain metastases from uterine cervical carcinoma (CC) and uterine endometrial carcinoma (EC). The findings of this review indicate the factors that can facilitate better treatment selection and, consequently, better outcomes in patients with CC and EC.

Reports on brain metastases (BMs) from uterine cervical carcinoma (CC) and uterine endometrial carcinoma (EC) have recently increased due to the development of massive databases and improvements in diagnostic procedures. This review separately investigates the prevalence, clinical characteristics, clinical presentation, diagnosis, treatment, and prognosis of BMs from CC and uterine endometrial carcinoma EC. For patients with CC, early-stage disease and poorly differentiated carcinoma lead to BMs, and elderly age, poor performance status, and multiple BMs are listed as poor prognostic factors. Advanced-stage disease and high-grade carcinoma are high-risk factors for BMs from EC, and multiple metastases and extracranial metastases, or unimodal therapies, are possibly factors indicating poor prognosis. There is no “most effective” therapy that has gained consensus for the treatment of BMs. Treatment decisions are based on clinical status, number of the metastases, tumor size, and metastases at distant organs. Surgical resection followed by adjuvant radiotherapy appears to be the best treatment approach to date. Stereotactic ablative radiation therapy has been increasingly associated with good outcomes in preserving cognitive functions. Despite treatment, patients died within 1 year after the BM diagnosis. BMs from uterine cancer remain quite rare, and the current evidence is limited; thus, further studies are needed.

• brain metastases
• cervical cancer
• endometrioid cancer
• prognosis
• treatment

Background and Objective: Chemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years particularly for advance stage CC. Bioinformatics analysis combined with experimental in vivo and in vitro data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. This study aims to investigate the prognostic value of family with sequence similarity 83, member A (FAM83A) gene and miR-206 in promoting CC progression and the involved genetic signaling pathways.

Method: This was a bioinformatic analysis study based on RNA sequencing data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and verification by in vivo and in vitro experimental data. It was designed to evaluate whether the aberrantly expressed gene signatures could serve as new potential biomarker to improve prognosis prediction in CC. The TCGA RNA sequencing data [306 cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma samples and 13 adjacent samples] and GEO data (GSE9750 and GSE52903 datasets) were integrated and performed a bioinformatics analysis.

Results: The results showed that CC-associated FAM83A gene serves as a key regulator of CC development and progression. Functionally, we observed that FAM83A is significantly overexpressed in CC, which is linked to poor overall survival as well as disease-free survival in CC patients. The in-vitro and in-vivo assessments performed after silencing FAM83A revealed that cell proliferation was significantly inhibited and the S-phase cell cycle arrest was induced. Mechanistically, FAM83A plays a role in PI3K/AKT signaling, and its downstream molecules could promote CC cell proliferation. Furthermore, functionality assessments by in-vitro luciferase reporter system and immunoblot analysis showed that miR-206 was the upstream of FAM83A and negatively correlated with FAM83A.

Conclusion: The miR-206/FAM83A/PI3K/AKT signaling pathway possibly serves as a critical effector in CC progression indicating the potential prognostic value of FAM83A gene as a novel biomarker for CC progression.

• FAM83A
• biomarker
• cervical cancer
• miR-206
• prognosis
• survival

Pathologically confirmed brain metastasis from primary cervical cancer is extremely rare. Herein, we report two cases of intracranial metastasis from cervical cancer that were histopathologically confirmed after surgical excision. In addition, we conducted a literature review to characterize the clinical manifestation, pathogenesis, and treatment of these patients.

Among the 1800 patients with primary cervical cancer who received therapy at our center from 2010 to 2018, two patients (0.1%) had definite histopathological evidence of brain metastasis. A 46-year-old female who had a history of poorly differentiated stage IIB cervical cancer with neuroendocrine differentiation presented with a solitary mass in the right occipital lobe 26 months after the initial diagnosis. She underwent surgery and chemotherapy but died of disease progression 9 months later. Another 55-year-old female diagnosed with poorly differentiated stage IVB cervical squamous cancer presented with a solitary mass in the right frontal lobe 16 months after simple hysterectomy. Twelve months later, multiple lesions were observed in the bilateral frontal-parietal lobe. The lesions were treated by surgery and stereotactic radiosurgery. The patient died of multiple organ failure 14 months later.

The pathogenesis and best management of brain metastasis from cervical cancer are not clear. Highly invasive subtypes or advanced cancer stages may be the key clinicopathological factors of brain metastasis. Surgical treatment is warranted in patients with a good health status and without metastasis to other sites.

• Brain metastasis
• Cervical cancer
• Chemotherapy
• Pathogenesis
• Radiotherapy

• cervical cancer
• gynaecological cancer
• palliative care
• radiotherapy

• Antineoplastic agents
• Biosimilar pharmaceuticals
• Diagnostic imaging
• Neoplasm metastases
• Neoplasm recurrence
• Uterine cervical neoplasms