Treatment Of Cervical Cancer Research Articles

Graphene oxide-enhanced photothermal therapy: laser parameter optimization and temperature modeling for hela cancer cell mortality.

Photothermal therapy, in which a laser is an effective tool, is a promising method for cancer treatment. Laser parameters, including power, irradiation time, type of laser radiation (continuous or chopped), and the concentration of the photothermal agent, can affect the efficiency of this method. Therefore, this study investigated and compared the effects of different laser parameters on the efficiency of photothermal treatment for cervical cancer, which is the fourth most prevalent cancer in women. In addition, we investigated the properties of graphene oxide (GO) synthesized as a photothermal agent under laser radiation, and its effectiveness in achieving the desired therapeutic temperature. This study examined and compared the effects of temperature, nanoparticle concentration, irradiation time, and laser power to understand their impact on heat transfer. The toxicity of graphene oxide at different concentrations in HeLa cancer cells was also evaluated. These results demonstrated low toxicity, particularly after 24h, with approximately 10% toxicity. The study explored mortality under laser irradiation at various powers and time intervals using continuous and chopped beam irradiation. In addition, a model for temperature prediction using a regression tree was presented. Finally, the combined photothermal effects of graphene oxide and laser irradiation were investigated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test results reveal significant effects, with a mortality rate of 90% in continuous radiation with a concentration of 0.3mg/ml and 75% in chopped beam irradiation with concentrations of 0.3 and 0.4mg/ml. A regression tree model was developed to predict temperature changes based on the GO concentration, laser power, and irradiation time, providing valuable insights for optimizing photothermal therapy parameters. Statistical analysis showed that the combined effect of graphene oxide with continuous laser irradiation was more effective than chopped-beam laser irradiation. However, the chopped-beam irradiation method is expected to cause less damage to surrounding tissues. These findings indicate that photothermal therapy with graphene oxide, chopped, and continuous laser irradiation can potently treat HeLa cancer cells and pave the way for further exploration of targeted cancer treatments.

Artificial intelligence in high-dose-rate brachytherapy treatment planning for cervical cancer: a review

Cervical cancer remains a significant global health concern, characterized by high morbidity and mortality rates. High-dose-rate brachytherapy (HDR-BT) is a critical component of cervical cancer treatment, requiring precise and efficient treatment planning. However, the process is labor-intensive, heavily reliant on operator expertise, and prone to variability due to factors such as applicator shifts and organ filling changes. Recent advancements in artificial intelligence (AI), particularly in medical image processing, offer significant potential for automating and standardizing treatment planning in HDR-BT. This review examines the progress and challenge of AI applications in HDR-BT treatment planning, focusing on automatic segmentation, applicator reconstruction, dose calculation, and plan optimization. By addressing current limitations and exploring future directions, this paper aims to guide the integration of AI into clinical practice, ultimately improving treatment accuracy, reducing preparation time, and enhancing patient outcomes.

The combined immunization of cervical cancer therapeutic vaccine based on Listeria balanced lethal system has a significant therapeutic effect on tumor model mice.

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer death in women. Effective treatment of cervical cancer is urgently needed. Tumor therapeutic vaccine is a research hotspot in tumor immunotherapy, and the tumor therapeutic vaccine based on attenuated live bacteria carrier has clinical application prospect because of its clear action site and high safety. The bacterial balanced lethal system uses nutritional screening instead of antibiotic screening to avoid the risk of the spread of antibiotic resistance. So it is generally recognized as a green carrier. In our early research, we have constructed two cervical cancer therapeutic vaccine candidates (LM-HPVCW-1 and LI-HPVCW-1) based on Listeria balanced lethal system via transforming the nutrient-deficient strains with nutrition gene complementary plasmid. The complementary plasmid contained the nutrition complementary gene, LM dal gene, and its Amp gene was replaced with asd gene to delete the antibiotic resistance. Besides, it carried the shuffled HPV-16 E6E7 fusion protein gene. In vitro experiments showed that the plasmid carried by the candidate strain could be stably passaged and the target protein could be successfully expressed. In this study, we proved that the two candidate strains were safe in vivo and induced cellular immune response. At the same time, by establishing a tumor-bearing mouse model, it was proved that the two vaccine strains combined immunization could effectively inhibit mouse tumors. The mechanism of tumor suppression may be related to breaking the immunosuppression of tumor microenvironment and inducing CD8+ T cell infiltration. The therapeutic vaccine for cervical cancer constructed in this study is expected to be further applied in clinical practice.

Targeted Delivery of SmacN7 Peptide Induces Immunogenic Cell Death in Cervical Cancer Treatment.

Cervical cancer is a common tumor in women and one of the common causes of cancer death in women. Due to the aggressive and non-specific nature of traditional chemotherapy, there is a growing need for new treatment modalities. Currently, tumor immunotherapy is increasingly garnering attention as a disruptive treatment approach. Therefore, we constructed CCTP-SmacN7, a delivery system capable of releasing active molecules in the tumor microenvironment. CCTP-SmacN7 can not only inhibit tumor proliferation and migration, but also induce tumors to produce large amounts of reactive oxygen species. The production of reactive oxygen species can activate tumors to release or expose damage-associated molecular patterns, promote DC cell maturation, and ultimately activate T cells. Here, we present an innovative targeted treatment approach for cervical cancer. While inducing tumor immunogenic cell death, this program can also improve the tumor microenvironment and initiate the tumor immune cycle.

Anti-cancer activity of synthetic gefitinib-1,2,3-triazole derivatives against Hela cells via induction of apoptosis

Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.

Focus Groups With Guatemalan Community Leaders About Barriers to Cervical Cancer Prevention and Control.

Cervical cancer is the leading cause of cancer-related death among Latin American women, including Guatemalans. This is troubling, given we have a vaccine, screening tool, and treatment for this preventable disease. Human papillomavirus (HPV) causes most cervical cancer. HPV self-testing is a viable option for women in low-resource areas, such as Guatemala. More information is needed about barriers to HPV self-testing. We conducted four focus groups (N = 43) in three locations in San Raymundo with female community leaders to assess the lived experience of their attitudes, practices, and knowledge about cervical cancer. Participants shared barriers they face receiving Pap tests, the HPV vaccine, and self-testing for HPV. We concluded culturally targeted information is needed about cervical cancer prevention, screening, and treatment. Policies should include outreach to marginalized populations in remote areas with low-literacy indigenous Mayans. Practices should include partnerships with lay midwives and health promoters to help Guatemalan women self-test for HPV.

Editorial Comment: Key Elements of Pelvic MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Editorial Comment: Key Elements of Pelvic MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Locally Advanced Cervical Cancer in a Patient with Epidermolysis Bullosa Treated with Concurrent Chemoradiotherapy and Electronic Brachytherapy

Purpose: The purpose of this report is to investigate the feasibility of combined modality treatment in a case of locally advanced cervical cancer in a patient with inherited epidermolysis bullosa as well as to suggest a protocol for cervical electronic brachytherapy. Materials and Methods: The patient was treated with image-guided external beam radiotherapy and concomitant chemotherapy to a dose of 45 Gy in 25 fractions with a simultaneously integrated boost of 55 Gy in involved lymph nodes. The maximal skin dose was 34.09 Gy. Intracavitary electronic brachytherapy was applied to the uterine cervix in 4 fractions of 7 Gy and contributed no dose to the skin. Results: The treatment was tolerated well with no early toxicity. During the 3-month period of follow-up, no adverse events of grade 2 or higher were detected, and no exacerbation of skin lesions was noted. Conclusions: This is the first report of treatment of cervical cancer in a patient with inherited epidermolysis bullosa where combined concurrent chemoradiotherapy and intracavitary electronic brachytherapy demonstrated feasibility and safety. The followed institutional protocol for treatment planning and delivery ensured low doses to organs and risk and reproducibility.

Advancing the Fight Against Cervical Cancer: The Promise of Therapeutic HPV Vaccines.

Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, particularly in developing countries with inadequate vaccine coverage and uptake. The development of therapeutic vaccines for HPV represents an emerging strategy that has the potential to bolster the fight against cervical cancer. Unlike current prophylactic vaccines designed to prevent new infections, therapeutic vaccines aim to eradicate or treat existing HPV infections, as well as HPV-associated precancers and cancers. This review focuses on clinical studies involving therapeutic HPV vaccines for cervical cancer, specifically in three key areas: the treatment of cervical intraepithelial neoplasia; the treatment of cervical cancer in combination with or without chemotherapy, radiotherapy, or immune checkpoint inhibitors; and the role of prophylaxis following completion of treatment. Currently, there are no approved therapeutic HPV vaccines worldwide; however, active progress is being made in clinical research and development using multiple platforms such as peptides, proteins, DNA, RNA, bacterial vectors, viral vectors, and cell-based, each offering relative advantages and limitations for delivering HPV antigens and generating targeted immune responses. We outline preferred vaccine parameters, including indications, target populations, safety considerations, efficacy considerations, and immunization strategies. Lastly, we emphasize that therapeutic vaccines for HPV that are currently under development could be an important new tool in fighting against cervical cancer.

Enhanced targeted treatment of cervical cancer using nanoparticle-based doxycycline delivery system

This study investigates a nanoparticle-based doxycycline (DOX) delivery system targeting cervical cancer cells via the CD44 receptor. Molecular docking revealed a strong binding affinity between hyaluronic acid (HA) and CD44 (binding energy: -7.2 kJ/mol). Characterization of the HA-Chitosan nanoparticles showed a particle size of 284.6 nm, a zeta potential of 16.9 mV, and a polydispersity index of 0.314, with SEM confirming smooth surface morphology. The encapsulation efficiency of DOX-loaded nanoparticles was 89.32%, exhibiting a sustained release profile, with 67.45% released over 72 h in acidic conditions (pH 5.5). Cytotoxicity assays demonstrated a significant reduction in HeLa cell viability to 22% at 72 h, compared to 67% in normal HEK cells. Stability tests confirmed the maintenance of nanoparticle integrity and a consistent drug release profile over three months. Cell migration was reduced by 45%, and RT-PCR analysis revealed a 53% downregulation of TNF-α expression, suggesting effective targeting of inflammatory pathways. These results underscore the potential of HA-Chitosan-based DOX nanoparticles in improving cervical cancer treatment through enhanced targeted delivery and inhibition of tumor-promoting mechanisms.

Development and pilot testing of INTERVENER, a web-based tool to match barriers to the cancer continuum organization to evidence-based interventions

BackgroundBarriers to the cancer continuum organization and interventions to approach them have been identified; however, there is a lack of a tool matching them. Our aim was to develop a web-based tool to identify the main barriers to the process of the cancer continuum organization, and propose matched evidence-based interventions (EBI) to overcome them.MethodsA questionnaire on barriers at six steps of the process of the cancer continuum organization was answered by collaborators. Each question included several options of barriers to be ranked. Barriers were organized in a framework based on the Tanahashi conceptual model, and were categorized in these dimensions: availability of services, accessibility, affordability, acceptability, user-provider interaction, governance, protocols and guidelines, information system, and quality assurance. Systematic searches were conducted on interventions for breast, cervical and colorectal cancer. Interventions were matched with the barriers they helped to overcome, and were classified in one of these groups for each barrier and cancer site: EBI as a single strategy, EBI within a multicomponent strategy, limited-evidence interventions, and macro level approaches. Barriers and interventions were matched on a web-based tool named INTERVENER, that allows the selection of up to 3 barriers for each step. It displays the visual representation of the selected barriers, the size of each dimension being proportional with the importance of that dimension as a barrier. Experts on different aspects of screening and cancer sites provided feedback on the tool. Collaborators from 41 countries worldwide tested it.ResultsThe tool matched 81 barriers with over 60 interventions. Collaborators reported the webpage to be organized logically (N = 17, 94%) and clearly formatted (N = 15, 83%). The tool was found useful for conducting a situational analysis of the barriers to cancer screening (N = 16, 89%), facilitating discussion with stakeholders on prioritization of interventions (N = 15, 83%), and planning their implementation (N = 15, 83%).ConclusionThis tool supports countries in conducting a systematic assessment of barriers, including their prioritization, and identifying EBI to overcome them, ultimately facilitating reduction of health inequalities. This tool can support governments, policymakers, managers, and healthcare providers to make better informed decisions to improve their cancer screening programmes.

CBX2 promotes cervical cancer cell proliferation and resistance to DNA-damaging treatment via maintaining cancer stemness.

Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancer-related death among women. Advanced stages and resistance to treatment in cervical cancer induce cancer-related deaths. Although epigenetics has been known to plays a vital role in tumor progression and resistance, the function of epigenetic regulators in cervical cancer is an area of investigation. In this study, we focused on an epigenetic regulator, polycomb repressor complex 1 (PRC1) in cervical cancer. Through bioinformatics analysis and immunochemistry, we subsequently identified CBX2, the deregulated subunit of PRC1, which is up-regulated in cervical cancer and associated with poor prognosis and unfavorable clinicopathological characteristics. We provided functional evidence demonstrating that CBX2 promoted cervical cancer cell proliferation. Furthermore, CBX2 exhibited an anti-apoptotic effect, which induced resistance to cisplatin and ionizing radiation in cervical cancer cells. Moreover, CBX2 was involved in maintaining cancer stemness. These findings suggest CBX2 plays an important role in cervical cancer progression and resistance to treatment, and may serve as a potential biomarker for prognosis and resistance as well as a potential therapeutic target.

Role of MRI in Assessing the Feasibility of Fertility-Sparing Treatments for Early-Stage Endometrial and Cervical Cancers.

Fertility-sparing treatment (FST) has become a key aspect of managing gynecologic cancers in reproductive-age patients who wish to preserve fertility. Several leading clinical societies, including the European Society of Gynecological Oncology, the European Society for Radiotherapy and Oncology, the European Society of Pathology, and the European Society of Human Reproduction and Embryology, have recently published evidence-based guidelines on fertility-sparing strategies and posttreatment surveillance of patients with early-stage gynecologic cancers, in particular endometrial and cervical cancers. These guidelines highlight MRI as essential to initial patient selection and follow-up. Properly tailored pelvic MRI protocols and clear MRI reports are key to performing accurate staging, assessing eligibility, and confirming the initial and ongoing feasibility of FST. Accordingly, radiologists, particularly those specializing in gynecologic imaging, play a critical role in the multidisciplinary approach to FST. They should be well-versed in FST eligibility criteria and key MRI finding before and after FST, ensuring these details are comprehensively communicated in structured MRI reports.

Barriers to early diagnosis and treatment of cervical cancer in Addis Ababa, Ethiopia: qualitative study

ObjectiveCervical cancer remains the most diagnosed and deadly cancer among women in low and middle income countries, including Ethiopia, although it can be controlled if detected and treated early. However,...

Advances in human papillomavirus detection for cervical cancer screening and diagnosis: challenges of conventional methods and opportunities for emergent tools.

Human papillomavirus (HPV) infection is the main cause of cervical cancer and other cancers such as anogenital and oropharyngeal cancers. The prevention screening and treatment of cervical cancer has remained one of the top priorities of the World Health Organization (WHO). In 2020, the WHO came up with the 90-70-90 strategy aimed at eliminating cervical cancers as a public health problem by the year 2030. One of the key priorities of this strategy is the recommendation for countries to ensure that 70% of their women are screened using a high-performance test by the age of 35, and again by the age of 45. Over the years, several traditional methods (notably, Pap smear and nucleic acid-based techniques) have been used for the detection of cervical cancer. While these methods have significantly reduced the incidence of cervical cancer and death, they still come short of excellence for the total eradication of HPV infection. The challenges include low sensitivity, low specificity, poor reproducibility, the need for high-level specialists, and the high cost of access to the facilities, to mention a few. Interestingly, however, several efforts are being made today to mitigate these challenges. In this review, we discussed the pros and cons of the traditional screening and testing of HPV infections, the efforts being made to improve their performances, and the emergent tools (especially, the electrochemical methods) that promise to revolutionize the screening and testing of HPV infections. The main aim of the review is to provide some novel clues to researchers that would allow for the development of high-performance, affordable, and triage-suitable electrochemical-based diagnostic tools for HPV and cervical cancer.

Ocular surface disease related to tisotumab vedotin-tftv.

To report a series of patients who developed ocular surface disease related to tisotumab vedotin-tftv (TV), an antibody-drug conjugate (ADC) approved for the treatment of recurrent or metastatic cervical cancer. This was a multicenter retrospective chart review study of patients who developed ocular surface disease related to TV between April 1st, 2022 to August 31st, 2023. Five patients were identified who developed ocular surface disease while on TV. All patients received a standard ocular adverse event prophylaxis regimen with each infusion per the product label, including a cool ocular compress, topical vasoconstrictor, topical steroid, and artificial tears. All five patients developed conjunctival subepithelial fibrosis. Two patients developed bilateral pseudomembranous conjunctivitis, one of whom subsequently developed conjunctival scarring. Two patients developed a bilateral culture positive conjunctivitis, which responded to topical antibiotics. One patient developed bilateral infectious keratitis and was treated with partial thickness corneal transplantation of both eyes. TV can be associated with ocular surface disease, including conjunctival scarring and infectious keratitis. Some cases may require surgical intervention. Oncologists and ophthalmologists should be aware of the possibility of these ocular complications, especially as more ADCs are approved. Further studies are required to determine toxicity mechanisms as well as optimal prophylaxis and management strategies.

Toripalimab combined with bevacizumab plus chemotherapy as first-line treatment for refractory recurrent or metastatic cervical cancer: a single-arm, open-label, phase II study (JS001-ISS-CO214).

To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3-28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6-95.3) and the DCR was 95.8% (95% CI=78.9-99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4-34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative first-line treatment option for patients with R/M CC. ClinicalTrials.gov Identifier: NCT04973904.

Cervical cancer stage distribution and survival outcomes in Africa: a systematic review and meta-analysis.

Cervical cancer is a leading cause of cancer-related deaths among women, with a disproportionate burden in sub-Saharan Africa. Understanding the cervical cancer stage and outcomes is crucial for developing effective interventions and reducing its burden. We aimed to undertake a systematic review and meta-analysis of cervical cancer stage distribution and survival outcomes in Africa. We searched MEDLINE, Embase, PubMed, Cochrane Library, Clarivate Analytics Web of Science, and the World Health Organization African Index Medicus database for publications in all languages from the inception of databases to July 2021. A total of 144 studies published between 1978 and 2021 from 33 African countries were included, encompassing 55,747 patients. We revealed that 53.3% (95% CI 50.9 to 55.6) of cervical cancer cases in Africa were diagnosed at late stages (stage III-IV). This proportion varied significantly across countries and regions, ranging from 7.7% to 86.3%. The study also highlighted disparities by Human Development Index (HDI) grouping, with low HDI countries exhibiting higher proportions of late-stage diagnoses (56.0%, 95% CI 51.6 to 60.4) compared with medium (51.2%, 95% CI 47.5 to 54.9) and high (50.7%, 95% CI 47.0 to 54.5) HDI countries. Notably, there was no stage migration observed over time (p = .53). The median overall survival was 24.0 months (interquartile range, 19.2-39.4). These stage and outcomes data highlight the need for expanding cervical cancer screening and treatment and are crucial for policymakers to develop evidence-based strategies aimed at accelerating the elimination of cervical cancer in Africa. Additionally, standardized data collection and reporting are needed to facilitate better monitoring of cervical cancer outcomes across countries.

Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques

Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques

Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer.

In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion. Nanofibers of two distinct poly[(d,l)-lactide-co-glycolide] (PLGA)-to-drug ratios (6:1 and 4:1) were manufactured through the electrospinning technology. The in vitro release behavior of imiquimod and metronidazole was evaluated via an elution method, while the in vivo discharge behavior was evaluated on a mice model. Additionally, a model of cervical cancer was established using C57BL/6J mice, and it was utilized to evaluate the efficacy of drug-eluting nanofibers through in vivo testing. Mice afflicted with cervical cancer were separated into three distinct groups for the study: The mice in Group A served as the control and received no treatment. Group B received treatment with pure PLGA nanofibers (no drugs loaded), whereas Group C received treatment with nanofibers loaded with imiquimod and metronidazole. Post implantation, the variations in tumor sizes of rats receiving the implantation of drug-eluting nanofibers were monitored. The experimental data show that drug-eluting nanofibers could discharge in vitro high concentrations of imiquimod and metronidazole for exceeding 30 days. In vivo, each membrane consistently released elevated concentrations of imiquimod/metronidazole at the intended site in mice over a four-week period, with minimal systemic drug concentration detected in the bloodstream. The mice treated with drug-loaded nanofibers displayed noticeably reduced tumor volumes compared to both the control group and the group treated with pristine nanofibers. Histological examination revealed the absence of any discernible tissue inflammation. Biodegradable nanofibers with a sustainable release of imiquimod and metronidazole demonstrated their effectiveness and lasting impact of treating mice with cervical cancer.