Cervical Cancer
Disease Details
Family Health Simplified
- Description
- Cervical cancer is a type of cancer that occurs in the cells of the cervix, the lower part of the uterus that connects to the vagina.
- Type
- Cervical cancer is not typically classified by genetic transmission. It primarily arises due to persistent infection with high-risk types of human papillomavirus (HPV). Although genetic factors may influence an individual's susceptibility to HPV infection and progression to cancer, cervical cancer is not inherited in a Mendelian fashion. Instead, it is largely considered to be caused by an external viral infection.
- Signs And Symptoms
- The early stages of cervical cancer may be completely free of symptoms. Vaginal bleeding, contact bleeding (one most common form being bleeding after sexual intercourse), or (rarely) a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs, or elsewhere.Symptoms of advanced cervical cancer may include loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures, and (rarely) leakage of urine or faeces from the vagina. Bleeding after douching or after a pelvic exam is a common symptom of cervical cancer.
- Prognosis
- The prognosis of cervical cancer largely depends on the cancer stage at diagnosis, the patient's overall health, and response to treatment. Early-stage cervical cancer generally has a favorable prognosis, with higher survival rates and a good chance of successful treatment. Advanced stages have a less favorable prognosis, with lower survival rates and a higher likelihood of recurrence. Regular screening and early detection are key to improving outcomes.
- Onset
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Onset: The onset of cervical cancer typically occurs in midlife, most commonly diagnosed in women between the ages of 35 and 44. It is rare in women under 20, and about 20% of cases are found in women over 65.
Nan: NAN is not a recognized term related to cervical cancer. If you meant a different abbreviation or term, please clarify. - Prevalence
- Cervical cancer is the fourth most common cancer in women worldwide. The prevalence varies significantly across different regions, with higher rates observed in low- and middle-income countries. Globally, there were an estimated 604,000 new cases and 342,000 deaths from cervical cancer in 2020.
- Epidemiology
- Worldwide, cervical cancer is both the fourth-most common cause of cancer and deaths from cancer in women. In 2018, 570,000 cases of cervical cancer were estimated to have occurred, with over 300,000 deaths. It is the second-most common cause of female-specific cancer after breast cancer, accounting for around 8% of both total cancer cases and total cancer deaths in women. About 80% of cervical cancers occur in developing countries. It is the most frequently detected cancer during pregnancy, with an occurrence of 1.5 to 12 for every 100,000 pregnancies.
- Intractability
- Cervical cancer is not generally considered intractable, especially when detected early. Early-stage cervical cancer can often be treated successfully with a combination of surgery, radiation therapy, and chemotherapy. Preventative measures, such as HPV vaccination and regular Pap smears, have significantly reduced the incidence and improve prognosis. Advanced stages are more challenging but can still be managed with aggressive and targeted therapies.
- Disease Severity
- Cervical cancer severity can be classified into different stages, ranging from early to advanced, and determining the severity typically involves staging based on factors such as the size of the tumor, the depth of invasion, and whether the cancer has spread to other parts of the body. Early-stage cervical cancer might have better treatment outcomes and lower risks, while advanced stages may present more significant health challenges and require more extensive treatment.
- Healthcare Professionals
- Disease Ontology ID - DOID:4362
- Pathophysiology
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Cervical cancer primarily arises from the transformation of normal cervical epithelial cells into malignant ones, typically driven by persistent infection with high-risk types of human papillomavirus (HPV). The pathophysiological process includes:
1. **HPV Infection**: High-risk HPV types, especially HPV-16 and HPV-18, infect the cervical epithelial cells.
2. **Viral Integration**: The viral DNA integrates into the host cell genome, disrupting normal cellular functions.
3. **Oncoprotein Expression**: HPV oncogenes (E6 and E7) produce proteins that inactivate tumor suppressor proteins (p53 and Rb), leading to uncontrolled cell division and inhibition of apoptosis.
4. **Cellular Transformation**: Chronic infection and genetic mutations cause pre-cancerous changes in the cervical cells, known as cervical intraepithelial neoplasia (CIN).
5. **Progression to Cancer**: If untreated, CIN can progress to invasive cervical cancer, characterized by the ability of cancer cells to invade the basement membrane and spread to surrounding tissues and distant organs.
Persistent HPV infection is a key factor in cervical carcinogenesis, with other co-factors such as smoking, immunosuppression, and long-term use of oral contraceptives also contributing to the risk. - Carrier Status
- Cervical cancer is not typically associated with a carrier status in the way genetic disorders are. It is primarily caused by persistent infection with high-risk types of human papillomavirus (HPV), especially HPV-16 and HPV-18. Regular screening and HPV vaccination are key preventive measures.
- Mechanism
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Cervical cancer primarily develops due to persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV-16 and HPV-18.
Mechanism:
1. HPV Infection: The virus infects the epithelial cells of the cervix.
2. Viral Integration: In high-risk HPV types, the viral DNA integrates into the host cell genome, disrupting normal cell regulatory processes.
3. Oncoprotein Production: The integrated HPV genome produces oncoproteins E6 and E7, which inactivate tumor suppressor proteins p53 and retinoblastoma protein (pRb) respectively.
4. Cellular Immortality: Inactivation of p53 and pRb leads to unregulated cell cycle progression and resistance to apoptosis, promoting cellular immortality.
Molecular Mechanisms:
1. E6 Oncoprotein: Binds to p53, leading to its degradation via the ubiquitin-proteasome pathway. This inhibits p53's role in DNA repair and apoptosis.
2. E7 Oncoprotein: Interacts with pRb, causing its degradation. This releases E2F transcription factors, driving the cell from the G1 to S phase uncontrollably.
3. Genomic Instability: The disruption of cell cycle control and apoptotic pathways causes genomic instability and accumulation of mutations.
4. Epigenetic Changes: HPV infection can also lead to changes in DNA methylation and histone modifications, further contributing to oncogenesis. - Treatment
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The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery and the emergence of fertility-sparing therapy in developed nations. Less advanced stages of cervical cancer typically have treatment options that allow fertility to be maintained if the patient desires.Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches. In addition, chemotherapy can be used to treat cervical cancer and is more effective than radiation alone. Chemoradiotherapy may increase overall survival and reduce the risk of disease recurrence compared to radiotherapy alone.Precancerous cells (cervical intraepithelial neoplasia) that would lead to cancer and early-stage cervical cancer (IA1) can be treated effectively by various surgical techniques. Surgical treatment methods include excision, where a cone-shaped portion of the cervix is removed, and ablation which removes only the parts with abnormal tissues. While these effectively reduce the risk of cancer developing or spreading, they cause an increased risk of premature birth in future pregnancies. Surgical techniques that remove more cervical tissue come with less risk of the cancer recurring but a higher chance of giving birth prematurely. Due to this risk, taking into account the age, childbearing plans of the woman, the size and location of the cancer cells are crucial for choosing the right procedure. There is low-certainty evidence that peri-operative care approaches, such as 'fast-track surgery' or 'enhanced recovery programmes' may lower surgical stress and improve recovery after gynaecological cancer surgery.Microinvasive cancer (stage IA) may also be treated by hysterectomy (removal of the whole uterus, including part of the vagina). For stage IA2, the lymph nodes are removed as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy. A systematic review concluded that more evidence is needed to inform decisions about different surgical techniques for women with cervical cancer at stage IA2.If a cone biopsy does not produce clear margins (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anaesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman consented. Due to the possible risk of cancer spreading to the lymph nodes in stage 1B cancers and some stage 1A cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.A radical trachelectomy can be performed abdominally or vaginally and opinions are conflicting as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who can conceive after surgery are susceptible to preterm labour and possible late miscarriage. A wait of at least one year is generally recommended before attempting to become pregnant after surgery. Recurrence in the residual cervix is rare if the trachelectomy has cleared the cancer. Yet, women are recommended to practice vigilant prevention and follow-up care, including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse. A Cochrane review has found moderate-certainty evidence that radiation decreases the risk of disease progression in people with stage IB cervical cancer, when compared to no further treatment. However, little evidence was found on its effects on overall survival.
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases. Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2–IIA). A Cochrane review found a lack of evidence on the benefits and harms of primary hysterectomy compared to primary chemoradiotherapy for cervical cancer in stage IB2.Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On 15 June 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.There is insufficient evidence whether anticancer drugs after standard care help women with locally advanced cervical cancer to live longer.For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope. This procedure is known as exenteration.No evidence is available to suggest that any form of follow‐up approach is better or worse in terms of prolonging survival, improving quality of life or guiding the management of problems that can arise because of the treatment and that in the case of radiotherapy treatment worsen with time. A 2019 review found no controlled trials regarding the efficacy and safety of interventions for vaginal bleeding in women with advanced cervical cancer.Tisotumab vedotin (Tivdak) was approved for medical use in the United States in September 2021. - Compassionate Use Treatment
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Compassionate use treatment for cervical cancer typically refers to the use of investigational drugs or therapies for patients who have not responded to standard treatments and have no other options available. These treatments are accessed through special programs and often require approval from regulatory authorities.
Off-label or experimental treatments for cervical cancer may include:
1. Immunotherapy: Drugs like pembrolizumab (Keytruda) are approved for various cancers and are sometimes used off-label for cervical cancer. Clinical trials are also examining new immunotherapies.
2. Targeted Therapy: Drugs targeting specific genetic markers or mutations in cancer cells are being tested. Bevacizumab (Avastin) is an example sometimes used off-label in combination with chemotherapy.
3. Adoptive Cell Transfer: Experimental treatments such as TIL (tumor-infiltrating lymphocytes) therapy are being investigated and may be available through clinical trials or compassionate use programs.
4. HPV Therapeutic Vaccines: Clinical trials are ongoing to develop vaccines that treat existing HPV infections and related cancers.
Access to these treatments typically requires enrollment in a clinical trial or application for compassionate use, and they should be discussed thoroughly with a healthcare provider. - Lifestyle Recommendations
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For cervical cancer, the following lifestyle recommendations can help in reducing the risk:
1. **HPV Vaccination**: Get vaccinated against the human papillomavirus (HPV), which is a significant risk factor for cervical cancer.
2. **Regular Screening**: Regular Pap smears and HPV tests can help detect precancerous conditions early.
3. **Safe Sexual Practices**: Use condoms and limit the number of sexual partners to reduce the risk of HPV infection.
4. **Smoking Cessation**: Avoid smoking, as tobacco can increase the risk of cervical cancer.
5. **Healthy Diet**: Consume a diet rich in fruits and vegetables, which can help support the immune system.
6. **Regular Exercise**: Stay physically active to maintain overall health.
7. **Limit Alcohol**: Excessive alcohol consumption can increase cancer risk, so it should be limited.
8. **Manage Stress**: Chronic stress can negatively impact the immune system, so managing stress through techniques like yoga and meditation is helpful.
Adopting these lifestyle habits can aid in prevention and early detection of cervical cancer. - Medication
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Cervical cancer treatment typically involves a combination of surgery, radiation therapy, and chemotherapy. Specific medications used in the treatment include:
1. **Chemotherapy:**
- Cisplatin
- Carboplatin
- Paclitaxel
- Topotecan
2. **Targeted Therapy:**
- Bevacizumab (Avastin)
Note: The choice of medication and treatment plan depends on the stage of cancer, overall health, and other individual factors. Always consult a healthcare professional for personalized medical advice. - Repurposable Drugs
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Repurposable drugs for cervical cancer are medications originally approved for other conditions that may show promise in treating cervical cancer. Some examples include:
1. **Metformin**: Initially used for type 2 diabetes, it has shown potential anti-cancer properties, including effects on cervical cancer cells.
2. **Aspirin**: Known for its anti-inflammatory properties, aspirin is being studied for its potential role in cancer prevention and treatment, including cervical cancer.
3. **Itraconazole**: An antifungal medication that has shown some anti-cancer effects in preclinical studies.
4. **Thalidomide**: Originally used for morning sickness, later repurposed for multiple myeloma, it has shown potential in inhibiting angiogenesis, which could be relevant for treating cervical cancer.
These drugs are still under investigation, and more research is needed to confirm their efficacy and safety in the context of cervical cancer. - Metabolites
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Cervical cancer can result in altered metabolic pathways and subsequently changes in specific metabolites. Commonly observed changes include alterations in glycolysis, amino acid metabolism, and lipid metabolism. Key metabolites associated with cervical cancer may include:
1. Lactate - Elevated levels due to increased glycolysis.
2. Alanine - Increased due to changes in amino acid metabolism.
3. Glutamine - Often upregulated for energy and biosynthesis.
4. Lipid metabolites (e.g., phospholipids) - Alterations reflect changes in cell membrane synthesis and signaling.
These metabolites can potentially be used as biomarkers for diagnosis or targets for therapy. - Nutraceuticals
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Nutraceuticals are products derived from food sources that offer additional health benefits beyond basic nutritional value. They may play a supportive role in cancer prevention and management. Common examples include antioxidants like vitamins C and E, curcumin from turmeric, and resveratrol found in grapes, which have shown potential in reducing cancer risk and supporting overall health.
Nanotechnology in cervical cancer involves the use of nanoparticles for targeted drug delivery, improving the effectiveness of treatments while minimizing side effects. Nanoparticles can be engineered to deliver chemotherapeutic agents directly to cancer cells, potentially enhancing treatment efficacy and reducing damage to healthy tissues. This approach is still under research but holds promise for future cervical cancer therapies. - Peptides
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In the context of cervical cancer, peptides and nanoparticles (nan) can play roles in both diagnosis and treatment:
1. **Peptides**:
- **Therapeutic Peptides**: Some therapeutic peptides are designed to target specific proteins involved in the growth of cervical cancer cells. These peptides can inhibit cancer cell proliferation or induce cell death.
- **Vaccine Development**: Peptides derived from HPV (Human Papillomavirus) proteins, such as E6 and E7 oncoproteins, are being used in therapeutic vaccines to elicit an immune response against HPV-infected cells, which can help control or eliminate cervical cancer.
2. **Nanoparticles**:
- **Drug Delivery**: Nanoparticles can be engineered to deliver anticancer drugs directly to cancer cells, enhancing the efficacy of the treatment and reducing side effects. This targeted approach ensures higher drug concentration at the tumor site.
- **Imaging**: Nanoparticles are also used in imaging to enhance the contrast in MRI or other imaging techniques, allowing for better visualization of the tumor and its margins.
Research in these areas is ongoing, with the goal of improving outcomes for patients with cervical cancer through more precise and effective interventions.