Clinical Outcomes and Dosimetric Evaluationof Interstitial Brachytherapyin Gynecological Malignancies.

BACKGROUND: In management of Carcinoma Cervix, Brachytherapy plays a crucial role. Most commonly used technique is Intracavitary Brachytherapy (ICBT). In cases where ICBT is not technically feasible or it may result in suboptimal dose distribution, Interstitial Brachytherapy (ISBT) is recommended. With this study we wanted to study the clinical outcome and dosimetric details of interstitial brachytherapy in gynecological cancers. MATERIALS & METHODS: We analysed clinicaloutcome and dosimetric details of interstitial brachytherapy (ISBT) done for gynecological malignancies in our institute during the period 1st January 2013 to 31st December 2020. RESULTS: Total of 42 interstitial brachytherapy (ISBT) details were analysed.37 patients had Carcinoma Cervix and 5 patients had Carcinoma Vagina. In the majority of the patients, ISBT dosage schedule was three fractions 7Gy each. D2cc to rectum, bladder, sigmoid and bowel were 4.88 Gy, 5.62 Gy, 3.57 Gy and 2.47 Gy respectively. Mean CTV volume was 129.89 cc. EQD2 dose to CTV combining EBRT and ISBT dose was 85.88 Gy. D90 and D100 to CTV from ISBT were 111.96% and 68.21 % of prescribed dose respectively. Grade III/IV toxicities were seen in 5 (12%) patients. Local control rates at 1year &2 years were 88% & 85.7% respectively. DFS at 1 year, 2 years and 3 years were 80.7%, 72.3% and 65.7% respectively. OS at 1year, 2 years, 4 years and 5 years were 92.5%, 65.5%, 59.5% and 42.3% respectively. CONCLUSION: 3D imagebased dosimetry with CT based planning using MUPIT implant is a feasible option for gynecological malignancies warranting interstitial brachytherapy. In view of good clinical outcomes in terms of toxicity profile, Local control, DFS and OS with acceptable GEC-ESTRO dosimetric data, we recommend routine use interstitial brachytherapy if facilities are available and in clinical situations were ISBT is indicated.

Culturally Competent Education and Human Papillomavirus Self-Sampling Achieves Healthy People 2030 Cervical Screening Target Among Low-Income Non-Hispanic Black and Hispanic Women.

PURPOSE: Disparities in cervical cancer screening, incidence, and mortality exist in the United States. Cervical cancer incidence and mortality rates in Texas are 20% and 32% higher, respectively, than national averages. Within Texas, these rates are significantly higher among non-Hispanic (NH) Black and Hispanic women. Cervical cancer screening uptake is lower among NH Black and Hispanic women (72.9% and 75.9%, respectively) compared with White women (85.5%) in Texas. METHODS: During March-August 2023, we conducted a pilot study that offered culturally competent education and human papillomavirus (HPV) self-sampling kits to women in two public housing projects in Houston, TX, that have predominantly NH Black or Hispanic residents. Among those eligible for cervical cancer screening, 35% (n = 24) of the NH Black and 34% (n = 16) of the Hispanic women were found to be underscreened per the US Preventive Services Task Force Guideline. We recruited 40 (24 NH Black and 16 Hispanic) eligible women for our study. The study was approved by the MD Anderson institutional review board and registered with ClinicalTrials.gov (NCT04614155-March 11, 2020). RESULTS: Seventy-five percent of the NH Black and 87% of the Hispanic participants completed the HPV self-sampling procedures per protocol. Samples of 17% NH Black and 12% Hispanic participants showed a performance error. Overall, cervical cancer screening uptake improved from 65% to 91% among NH Black and from 66% to 96% among Hispanic participants. CONCLUSION: Culturally competent education and HPV self-sampling resulted in remarkable improvement in cervical cancer screening uptake among underscreened NH Black and Hispanic women residents of Houston public housing projects. Implementing this strategy could significantly reduce cervical cancer incidence and mortality among similar populations in the United States and globally.

Analysis of the diagnostic performance of PAX1/SOX1 gene methylation in cervical precancerous lesions and its role in triage diagnosis.

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.

HPV genotyping in clinical samples using long-read single-molecule real-time sequencing.

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high-risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real-time sequencing (SMRT) and evaluated its performance against MY09-11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09-11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR-HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR-HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype.

Shared Decision Making in Oncology and Its Implementation in Cervical Cancer Management in the Philippines: A Narrative Review.

PURPOSE: Shared decision making (SDM) is an approach where clinicians and patients make decisions together using the best available evidence. Although much studied, recognized to be ethically imperative, and recommended in international health policies, it remains poorly implemented. In the Philippines, there are limited studies on patient decision making preferences and SDM. Practical guidance on the implementation of SDM or use of patient decision aids (PtDAs) is often not detailed in existing national clinical practice guidelines in oncology. METHODS: We performed a systematic search of Philippine literature on SDM in oncology and an iterative review of international literature on the philosophy and methods of SDM, the utility and effectiveness of PtDAs, and the facilitators and barriers to implementation or usage. We contextualized our review to the cervical cancer management and health service delivery in the Philippines. RESULTS: Local literature is limited to five scientific publications and two registered studies. International literature encompasses patient decisional preferences, the role of PtDAs and the standards for their development and evaluation, their effectiveness, and barriers and facilitators to their use in cancer-related decision making. We discussed the implications on the management of cervical cancer in the Philippines, challenges in health service delivery and standards, and SDM research. CONCLUSION: Local SDM research is limited. Our preliminary experience in a multicenter clinical trial in Manila on PtDA use in the framework of SDM in cervical cancer suggest good patient and clinician acceptability. Challenges to implementation such as unfavorable financial situations, urgency of clinical decisions, low patient or caregiver educational attainment, and poor integration of multidisciplinary and SDM in organizational workflows will be important when implementing SDM in different settings.

Enhancing cervical cancer detection and robust classification through a fusion of deep learning models.

Cervical cancer, the second most prevalent cancer affecting women, arises from abnormal cell growth in the cervix, a crucial anatomical structure within the uterus. The significance of early detection cannot be overstated, prompting the use of various screening methods such as Pap smears, colposcopy, and Human Papillomavirus (HPV) testing to identify potential risks and initiate timely intervention. These screening procedures encompass visual inspections, Pap smears, colposcopies, biopsies, and HPV-DNA testing, each demanding the specialized knowledge and skills of experienced physicians and pathologists due to the inherently subjective nature of cancer diagnosis. In response to the imperative for efficient and intelligent screening, this article introduces a groundbreaking methodology that leverages pre-trained deep neural network models, including Alexnet, Resnet-101, Resnet-152, and InceptionV3, for feature extraction. The fine-tuning of these models is accompanied by the integration of diverse machine learning algorithms, with ResNet152 showcasing exceptional performance, achieving an impressive accuracy rate of 98.08%. It is noteworthy that the SIPaKMeD dataset, publicly accessible and utilized in this study, contributes to the transparency and reproducibility of our findings. The proposed hybrid methodology combines aspects of DL and ML for cervical cancer classification. Most intricate and complicated features from images can be extracted through DL. Further various ML algorithms can be implemented on extracted features. This innovative approach not only holds promise for significantly improving cervical cancer detection but also underscores the transformative potential of intelligent automation within the realm of medical diagnostics, paving the way for more accurate and timely interventions.

[Research progress on the differences between T and B cell responses to three different forms of human papilloma virus (HPV) vaccination].

One of the most prevalent malignancies in women is cervical cancer. Cervical cancer is mostly brought on by chronic high-risk human papillomavirus 16 (HPV16) and HPV18 infection. Currently, the widely used HPV vaccines are the bivalent Cervarix, the tetravalent Gardasil, and the 9-valent Gardasil-9.There are differences in T cell effector molecule changes, B cell antibody level, duration, age and the injection after vaccination of the three vaccines.

Cervical cancer screening practices in HIV positive females - a missing link in health care delivery in Pakistan.

Objectives: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001). CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.

Cancer screening research in Bangladesh: Insights from a scoping review.

This scoping review summarises the findings of research conducted on cancer screening in Bangladesh, including the prevalence, awareness, barriers, and evaluation of screening programmes, by performing a comprehensive search of electronic databases and gray literature. 25 studies that met inclusion criteria were included in the final analysis. Most of the studies were about screening for cervical cancer, were quantitative, were cross-sectional, and were conducted in hospital settings. The main challenges to screening uptake were shyness, fear, a lack of knowledge, and an inadequate understanding of the concept of screening. Visual inspection with acetic acid (VIA) was found to be a simple and cost-efficient way to detect early-stage cervical cancer. However, breast self-examination (BSE) was reported to be insufficient. Education was found to have a positive impact on cancer screening knowledge and practice, but more needs to be done to improve screening rates, such as the utilisation of media, particularly in rural areas. The results of this scoping review highlight Bangladesh's low cancer screening prevalence and uptake and suggest that targeted awareness campaigns and enhanced access to screening services are required to increase cancer screening uptake and reduce the cancer burden in Bangladesh.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Evaluation of cancer screening services provided for people living with HIV in Botswana, 2022-2023.

People living with human immunodeficiency virus (PLHIV) have an increased risk of cancers. Currently, Botswana has no screening guidelines for common cancers in PLHIV except cervical cancer. Also, the proportion of PLHIV who are screened for cancer is unknown. This study aimed to evaluate cancer screening services for PLHIV receiving care in the human immunodeficiency virus (HIV) clinics. Resources for cancer screening were assessed and medical records of adults initiating antiretroviral therapy (ART) from 2020 to 2021 in 20 high-volume HIV clinics in Gaborone and Francistown were reviewed. Questionnaires assessing knowledge and practices of cancer screening were administered to health workers. The majority of clinics had the required resources for cancer screening (specifically cervical cancer). Of the 62 health workers working at the HIV clinics, 57 (91.9%) completed the questionnaire: 35 (62.5%) nurses and 22 (37.5%) doctors. Only 26.3% of the health workers were trained in cervical cancer screening. Doctors were more likely to report practicing routine screening of other cancers (e.g. breast) (p = 0.003) while more nurses reported assessing patients for cancer history during follow-up visits (p = 0.036). Most health workers did not perform physical examinations to detect cancer at initial or follow-up visits. Of the 1000 records of PLHIV reviewed, 57.3% were females, and only 38% of these were screened for cervical cancer. Besides cervical cancer, almost all (97.8%) were not screened for any cancer at ART initiation and during follow-up. These findings highlight the need to improve cancer screening services of PLHIV in Botswana through the training of health workers, and the development and enhanced use of screening guidelines.

M6A-induced transcription factor IRF5 contributes to the progression of cervical cancer by upregulating PPP6C.

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer growth.

The objective of this study was to better characterize the role of the glutamine transporter SLC38A1 in cervical cancer and explore the underlying mechanisms. Data from public databases and clinical cervical cancer tissue samples were used to assess the expression of SLC38A1 and its prognostic significance. Immunohistochemical staining, qRT-PCR, and Western blotting were used to evaluate the expression of relevant genes and proteins. Cell viability, cell cycle, apoptosis, and intracellular glutamine content were measured using CCK-8, flow cytometry, and biochemical assays. Additionally, the RNA immunoprecipitation (RIP) assay was used to examine the impact of METTL3/IGF2BP3 on the m6A modification of the SLC38A1 3'UTR. Both cervical cancer specimens and cells showed significantly increased expression of SLC38A1 and its expression correlated with an unfavorable prognosis. Knockdown of SLC38A1 inhibited cell viability and cell cycle progression, induced apoptosis, and suppressed tumor growth in vivo. Glutaminase-1 inhibitor CB-839 reversed the effects of SLC38A1 overexpression. METTL3 promoted m6A modification of SLC38A1 and enhanced its mRNA stability through IGF2BP3 recruitment. Moreover, METTL3 silencing inhibited cell viability, cell cycle progression, intracellular glutamine content, and induced apoptosis, but these effects were reversed by SLC38A1 overexpression. In conclusion, METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer progression. SLC38A1 inhibition is a potential therapeutic strategy for cervical cancer.

Effectiveness of sentinel lymph node biopsy and bilateral pelvic nodal dissection using methylene blue dye in early-stage operable cervical cancer-A prospective study.

OBJECTIVE: To evaluate the effectiveness of methylene blue dye in detecting sentinel lymph nodes (SLNs) in women with early-stage operable (defined as FIGO I-IIA) cervical cancer. It also aims to evaluate procedural challenges and accuracy. METHOD: This prospective study, which focused on 20 women with early-stage cervical cancer, was carried out between June 2016 and December 2017. These patients had SLN mapping with methylene blue dye injections and thorough examinations, including imaging. All patients underwent radical hysterectomy and complete bilateral pelvic lymphadenectomy. No additional investigation was done on the lymph node in cases where a metastasis was found in the first H&E-stained segment of the sentinel node. RESULT: 20 patients were included in the analysis. The median age of the subjects was 53, and 95 % of them had squamous cell carcinoma. 90 % of the time, the identification of SLNs was effective, and 55 SLNs were found, of which 52.7 % were on the right side of the pelvis and 47.3 % on the left. The obturator group had the most nodes, followed by the external and internal iliac groups in descending order of occurrence. Metastasis was detected in 3 patients, resulting in a sensitivity of 100 % and a specificity of 93.75 % for SLN biopsy. Notably, no false-negative SLNs were found. Complications related to methylene blue usage included urine discoloration in 30 % of patients. CONCLUSION: This trial highlights the promising efficacy and safety of methylene blue dye alone for SLN identification in early-stage operable cervical cancer, with a notably higher success rate. Despite limitations like a small sample size, healthcare professionals and researchers can build upon the insights from this study to enhance cervical cancer management.

METTL14 decreases FTH1 mRNA stability via m6A methylation to promote sorafenib-induced ferroptosis of cervical cancer.

Cervical cancer (CC) is a prevalent malignancy among women worldwide. This study was designed to investigate the role of METTL14 in sorafenib-induced ferroptosis in CC. METTL14 expression and m6A methylation were determined in CC tissues, followed by analyzes correlating these factors with clinical features. Subsequently, METTL14 was knocked down in CC cell lines, and the effects on cell proliferation, mitochondrial morphology and ferroptosis were assessed using CCK-8, microscopy, and markers associated with ferroptosis, respectively. The regulatory relationship between METTL14 and FTH1 was verified using qRT-PCR and luciferase reporter assays. The functional significance of this interaction was further investigated both in vitro and in vivo by co-transfecting cells with overexpression vectors or shRNAs targeting METTL14 and FTH1 after sorafenib treatment. METTL14 expression and m6A methylation were significantly reduced in CC tissues, and lower METTL14 expression levels were associated with a poorer CC patients' prognosis. Notably, METTL14 expression increased during sorafenib-induced ferroptosis, and METTL14 knockdown attenuated the ferroptotic response induced by sorafenib in CC cells. FTH1 was identified as a direct target of METTL14, with METTL14 overexpression leading to increased m6A methylation of FTH1 mRNA, resulting in reduced stability and expression of FTH1 in CC. Furthermore, FTH1 overexpression or treatment with LY294002 partially counteracted the promotion of sorafenib-induced ferroptosis by METTL14. In vivo xenograft experiments demonstrated that inhibiting METTL14 reduced the anticancer effects of sorafenib, whereas suppression of FTH1 significantly enhanced sorafenib-induced ferroptosis and increased its anticancer efficacy. METTL14 reduces FTH1 mRNA stability through m6A methylation, thereby enhancing sorafenib-induced ferroptosis, which contributes to suppressing CC progression via the PI3K/Akt signaling pathway.