Cervix Carcinoma
Disease Details
Family Health Simplified
- Description
- Cervical carcinoma, commonly referred to as cervical cancer, is a malignant tumor of the cervix, the lowermost part of the uterus that connects to the vagina, primarily caused by persistent infection with high-risk human papillomavirus (HPV) types.
- Type
- Cervical carcinoma is a type of cancer that occurs in the cells of the cervix. The type of genetic transmission for cervical carcinoma is not purely hereditary; it is primarily associated with infection by high-risk types of human papillomavirus (HPV), which is a sexually transmitted infection. However, genetic susceptibility factors may play a role in an individual's risk of developing the disease.
- 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
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Cervical carcinoma, commonly referred to as cervical cancer, prognosis varies based on the stage at diagnosis, the specific type of cervical cancer, and the overall health of the patient.
1. **Early-Stage Diagnosis:** Prognosis is generally favorable. The 5-year survival rate for localized cervical cancer (confined to the cervix) is about 92%.
2. **Regional Spread:** If the cancer has spread to nearby tissues or lymph nodes, the 5-year survival rate drops to approximately 56%.
3. **Distant Spread:** For cases where cervical cancer has metastasized to distant parts of the body, the 5-year survival rate is around 17%.
Early detection and treatment significantly improve the prognosis. Regular screenings and HPV vaccinations are crucial preventive measures. Treatment options such as surgery, radiation therapy, and chemotherapy can also influence outcomes. - Onset
- Cervix carcinoma (cervical cancer) often has a gradual onset. In its early stages, there may be no symptoms. As it progresses, symptoms might include abnormal vaginal bleeding (such as bleeding after sex, between periods, or after menopause), pelvic pain, or pain during intercourse. Monitoring through routine Pap tests and HPV screening is crucial for early detection.
- Prevalence
- Cervical carcinoma, commonly known as cervical cancer, is less common in developed countries due to widespread screening programs and the HPV vaccination. Globally, it remains a significant health issue, particularly in low- and middle-income countries. The prevalence of cervical cancer varies widely depending on the region, with higher rates in areas with limited access to preventive care. It is the fourth most common cancer in women worldwide.
- 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 carcinoma, particularly in its early stages, can often be treated successfully. Treatment options may include surgery, radiation therapy, chemotherapy, or a combination of these approaches. Early detection through regular screening like Pap smears and HPV tests significantly improves the prognosis. However, once cervical carcinoma progresses to advanced stages, it can become more challenging to treat and manage, potentially leading to intractability.
- Disease Severity
- Cervix carcinoma, also known as cervical cancer, varies in severity based on its stage. Early stages (Stage I and II) are generally more treatable and have a better prognosis. Advanced stages (Stage III and IV) are more severe, often involving the spread to nearby tissues or distant organs, and have a worse prognosis. Early detection through regular screening such as Pap smears can significantly improve outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:2893
- Pathophysiology
- Pathophysiology of Cervix Carcinoma: Cervical carcinoma typically arises from the epithelial cells of the cervix, most commonly progressing through a series of precancerous changes known as cervical intraepithelial neoplasia (CIN). The primary causal factor is persistent infection with high-risk human papillomavirus (HPV) types, particularly HPV-16 and HPV-18. The infection leads to the integration of viral DNA into the host genome, which disrupts normal cell cycle regulation by inactivating tumor suppressor proteins like p53 and retinoblastoma protein (pRb). This results in uncontrolled cell proliferation, genomic instability, and, eventually, malignant transformation. Chronic inflammation and immune evasion mechanisms also play roles in the pathogenesis of cervical cancer.
- Carrier Status
- Cervical carcinoma, more commonly known as cervical cancer, is not typically associated with a hereditary "carrier status" in the same way that some genetic diseases are. Instead, it's primarily linked to persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV-16 and HPV-18. Regular screening through Pap smears and HPV testing is crucial for early detection and prevention. HPV vaccination is highly effective in reducing the risk of cervical cancer.
- Mechanism
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Cervical carcinoma, primarily caused by persistent infection with high-risk human papillomavirus (HPV) types (e.g., HPV 16 and 18), involves several key mechanisms and molecular pathways:
**Mechanism:**
1. **HPV Infection:** The introduction of high-risk HPV into cervical epithelial cells.
2. **Viral Persistence:** Failure to clear the virus leads to persistent infection.
3. **Integration:** High-risk HPV DNA integrates into the host genome, disrupting normal cellular function.
**Molecular Mechanisms:**
1. **Oncoproteins E6 and E7:**
- **E6 Protein:** Binds to and facilitates the degradation of the tumor suppressor protein p53, preventing apoptosis.
- **E7 Protein:** Binds to the retinoblastoma protein (pRb), leading to its degradation. This releases E2F transcription factors, promoting uncontrolled cell division.
2. **Genomic Instability:** Integration and the resulting disruption of cellular genes cause genomic instability, leading to further mutations and chromosomal aberrations.
3. **Immune Evasion:** HPV’s E6 and E7 can modulate immune responses, helping infected cells evade immune surveillance.
4. **Cellular Immortalization:** The inhibition of p53 and pRb pathways contributes to cellular immortalization, a hallmark of cancer cells.
5. **Angiogenesis and Metastasis:** Expression of angiogenic factors and invasion-promoting proteases are upregulated, aiding tumor growth and spread.
These molecular alterations cumulatively drive the transformation of normal cervical epithelial cells into malignant carcinoma. - 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 carcinoma typically involves accessing investigational drugs or therapies that are not yet approved by regulatory authorities. This option is generally considered when standard treatments have failed, and the patient has no other viable options. Compassionate use requests are evaluated on a case-by-case basis.
Off-label or experimental treatments for cervical carcinoma can include:
1. Immunotherapy: Drugs such as pembrolizumab (Keytruda) have shown promise in treating advanced cervical cancers by targeting the PD-1/PD-L1 pathway.
2. Targeted Therapy: Agents like bevacizumab (Avastin) are sometimes used off-label to inhibit angiogenesis in cervical cancer.
3. Clinical Trials: Participation in clinical trials can provide access to experimental treatments such as new chemotherapies, combination therapies, or novel targeted agents.
These treatments should be discussed thoroughly with an oncologist who can provide guidance based on the latest research and individual patient circumstances. - Lifestyle Recommendations
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For cervical carcinoma, lifestyle recommendations include:
1. **Regular Screening:** Undergo regular Pap smears and HPV testing as recommended by your healthcare provider to detect early changes in cervical cells.
2. **HPV Vaccination:** Get vaccinated against human papillomavirus (HPV), which is a major cause of cervical cancer.
3. **Safe Sexual Practices:** Use condoms and limit the number of sexual partners to reduce the risk of HPV infection.
4. **Quit Smoking:** Avoid smoking, as it is linked to an increased risk of cervical cancer.
5. **Healthy Diet:** Maintain a balanced diet rich in fruits, vegetables, and whole grains to support overall immune health.
6. **Regular Exercise:** Engage in regular physical activity to maintain a healthy weight and improve overall well-being.
7. **Avoid Long-term Oral Contraceptives Use:** Consult with a healthcare provider regarding the use of oral contraceptives for extended periods, as they may increase the risk.
8. **Manage Other Health Conditions:** Address and manage other health issues, such as HIV or chlamydia, which can increase the risk of cervical cancer.
Implementing these recommendations can help reduce the risk of cervical carcinoma and support overall health. - Medication
- For cervical carcinoma, commonly used medications include chemotherapy agents such as cisplatin, carboplatin, paclitaxel, and topotecan. Targeted therapies, such as bevacizumab, may also be used. Treatment decisions depend on the stage, size, and spread of the cancer, as well as patient-specific factors. It is important for patients to consult with their oncologist to determine the most appropriate treatment plan.
- Repurposable Drugs
- No specific information on repurposable drugs for cervix carcinoma is available with the provided context. Repurposable drugs are existing medications used for other conditions that may show efficacy against cervical cancer, but identification and validation require detailed research and clinical trials. Common treatment options for cervical cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Consultation with a medical professional is essential for personalized treatment plans.
- Metabolites
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Cervix carcinoma, also known as cervical cancer, can be associated with several metabolic changes. Commonly reported altered metabolites in cervical cancer include:
1. Glucose: Increased glycolysis can lead to elevated glucose uptake.
2. Lactate: Higher lactate production due to anaerobic glycolysis (Warburg effect).
3. Amino acids: Altered levels of amino acids such as glutamine, alanine, and glycine.
4. Lipids: Changes in lipid metabolism including sphingolipids and phospholipids.
5. Nucleotide metabolites: Alterations in purine and pyrimidine metabolism.
These metabolic alterations can serve as potential biomarkers for diagnosis, prognosis, and therapeutic targets. - Nutraceuticals
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For cervical carcinoma, nutraceuticals—dietary supplements intended to provide health benefits—are being explored for their potential in prevention and adjunctive treatment. These include vitamins (such as folic acid and vitamin E), antioxidants (like curcumin and resveratrol), and other plant-derived compounds with anti-inflammatory and immune-boosting properties.
The use of nanotechnology (nanomedicine) in treating cervical carcinoma involves creating nanoparticles for more precise drug delivery, minimizing side effects, and improving the efficacy of chemotherapy and radiotherapy. These strategies are still largely experimental but show promising results in early studies for targeting cancer cells more effectively. - Peptides
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For cervical carcinoma, also known as cervical cancer, peptide-based therapies and nanotechnology are emerging areas of research and treatment.
**Peptides:**
Peptide vaccines and therapeutic peptides are being explored to help stimulate the immune system to recognize and destroy cancer cells. Examples include HPV (Human Papillomavirus) peptides used in vaccines to provoke an immune response against HPV proteins, which are implicated in the development of cervical cancer. Therapeutic peptides might also be engineered to specifically target cancer cells without harming normal cells.
**Nanotechnology:**
Nanotechnology offers innovative approaches for the detection, diagnosis, and treatment of cervical carcinoma. Examples include:
- **Nanoparticles for Drug Delivery:** Nanoparticles can be designed to deliver chemotherapeutic agents directly to cancer cells, increasing drug efficacy and reducing side effects.
- **Nanosensors:** Advanced nanosensors can detect biomolecules associated with cervical cancer at very low concentrations, aiding in early diagnosis.
- **Photothermal Therapy:** Nanoparticles can be used to convert light into heat to target and kill cancer cells selectively.
Both peptides and nanotechnology are promising fields that offer potential advancements in the management and treatment of cervical carcinoma.