Cervical cancer remains one of the most prevalent gynecologic cancers in the world. According to the most recent data, it ranks 14th among all malignancies and 4th among women globally. The primary and secondary emphasis of cervical cancer intervention is primary and secondary prevention.

Primary prevention and screening are the most effective techniques for reducing cervical cancer incidence and mortality. In the US and other developing nations, the majority of screening and diagnostic efforts focus on early detection of HPV lesions by HPV testing and Pap smears.

Although HPV testing is not advised for women under 30 years of age, the United States Preventive Services Task Force recommends that low-risk younger women begin screening with Pap smears at age 21. Women at risk are recommended to continue these tests until the age of 65.

Based on earlier results and the use of these tests and more recent guidelines suggest screening intervals of 3 to 5 years. Because cervical cancer is caused by a STI, it is avoidable. Education, consistent screenings, and effective interventions can reduce the burden of this disease. Just like other diseases and cancers,

In the United States, African American women have a significantly higher cervical cancer mortality rate. Since 2006, vaccines to help prevent cervical cancer have been accessible. Vaccination can reduce cancer mortality rates in nations with limited resources which don’t have the resources for regular screenings and have higher fatality rates.

More than 500,000 new instances of cervical cancer are diagnosed annually on a global scale. Cervical Cancer claims around 250,000 lives every year. Women in areas with scarce resources, Hispanics, and African American women have lower rates of evidence-based care and a significantly higher death rate than women in other demographic groups. HPV, the virus which causes cervical cancer is an STI.

Mortality rate is much higher in women who have not been screened in the past 5 years for cervical cancer. The lack of regular follow-ups after being diagnosed with a precancerous lesion is another factor that drives up the mortality rate. Ongoing trends suggest that women with highest risk of mortality are perhaps less likely to get vaccinated.

The causal agent of cervical cancer is HPV. Over 75% of cases are significantly related to high-risk HPV 16 and 18. Although more than 500,000 cases of HPV are diagnosed annually, most cases are low-grade infections that cure on their own within two years.

According to current research, Human Papillomavirus (HPV) is present in most sexually active individuals sometime in their lives. There are around 130 recognized kinds of HPV, 20 of which have been linked to cancer.

Cervical dysplasia rates associated with HPV are solely known in women, as men are not examined outside of study protocols. HPV 16 and 18 are the most prevalent types of HPV detected in invasive cervical cancer.

Most cases of high-risk HPV occur in women under the age of 25 — various studies suggest that most cases of HPV do not lead to cancer in women aged above 25. Nevertheless, co-infection may reduce the likelihood of spontaneous clearance and cancer progression.

Some factors which increase the risk for Cervical cancer and contracting HPV are:

• Use of oral contraceptives
• Herpes Simplex Virus
• HIV
• Other genital illnesses like chlamydia
• More than 1 sexual partner
• Smoking

HPV is transmitted through skin-to-skin contact, which includes sexual contact, hand-to-genital organ touch, and oral sex.

Vaccines are around 90% effective against HPV. HPV patients who have been diagnosed late have an exponentially higher possibility of developing cervical cancer than individuals who are screened regularly, so inconsistent screening is a significant risk factor for cervical cancer.

According to the SEER database, 5-year survival rates are determined by the extent of the spread of cancer in the body. If the cancer is localized the survival rate is 92%; if the cancer has spread to lymph nodes near the uterus and cervix it is 58%; and it’s approximately 18% when distant parts of the body and organs near the cervix have been affected by the cancer.

Factors which affect significantly affect outcomes in patients with cervical cancer are:

• Stage of diagnosis
• Age
• Size of tumor during diagnosis
• Quality of the delivery of evidence-based care
• Extent of the spread of cancer in lymph nodes

Age Group:

• Although women of all ages can be affected by cervical cancer, women around the years of 35 and 44 are the ones who receive the majority of diagnoses.
• Age-related increases in the risk of cervical cancer are noted, with women over 50 having the highest incidence.

Associated Comorbidities or Activity:

• Human Papillomavirus (HPV) Infection: Persistent infection with high-risk types of HPV, especially HPV-16 and HPV-18, is the most significant risk factor for the development of cervical cancer.
• Smoking: Tobacco use, mainly smoking, is associated with an increased risk of cervical cancer.
• Immunosuppression: People who use immunosuppressive medicines or have HIV/AIDS may be more vulnerable because of their compromised immune systems.

Clinical Presentation:

• Early Stages (Precancerous Lesions): Cervical dysplasia, or precancerous changes in the cells of the cervix, may not cause noticeable symptoms. These are often detected through routine Pap smears or HPV testing.

Advanced Stages:

• Abnormal Vaginal Bleeding: The most prevalent and obvious sign is irregular vaginal bleeding. This can include bleeding following menopause, following sexual activity, or in between cycles.
• Pelvic Pain: As the cancer progresses, it may cause pelvic pain or discomfort.
• Painful Urination or Blood in Urine: Advanced cervical cancer may affect the bladder, causing pain during urination or blood in the urine.
• Weight Loss and Fatigue: General symptoms such as weight loss, fatigue, and a general sense of illness may be present in advanced stages.

Acuity of Presentation:

• Early Stages: Both cervical dysplasia and cancer of the cervix may not exhibit any signs in the early stages. Regular screenings are essential for early identification and treatment, such as HPV tests and Pap smears.
• Advanced Stages: The symptoms become more pronounced and problematic in advanced stages, making the cancer more clinically evident. However, the acuity can vary, and some individuals may present with more severe symptoms than others.

Pelvic Examination:

• Speculum Examination: A speculum is used to visualize the cervix. The healthcare provider inspects the cervix for any abnormalities, such as changes in color, size, or shape.
• Visual Inspection: The healthcare provider visually assesses the cervix for any visible lesions, ulcers, or irregularities.

Bimanual Examination:

• Digital Examination: The healthcare provider inserts one or two fingers into the vagina while simultaneously palpating the abdomen with the other hand. This allows them to assess the size, shape, and mobility of the uterus and ovaries.
• Uterine Mobility: Reduced mobility of the cervix or uterus may suggest involvement of adjacent structures by the tumor.

Rectovaginal Examination:

• Evaluation of the Rectum and Posterior Vagina: The healthcare provider may perform a rectovaginal examination by inserting a finger into the rectum while simultaneously palpating the posterior vaginal wall. This helps assess the involvement of the rectum and the extent of the tumor.

Assessment of Parametrial Involvement:

• Parametrial Assessment: The healthcare provider assesses the parametrial tissues for any signs of involvement. Parametrial involvement may indicate more advanced disease.

Lymph Node Examination:

• Palpation of Lymph Nodes: The healthcare provider may palpate inguinal, pelvic, and sometimes abdominal lymph nodes to check for enlargement, which could suggest the spread of cancer to the lymphatic system.

Evaluation of Bladder and Bowel Function:

• Assessment of Bladder Function: In advanced cases, cervical cancer may invade the bladder, leading to symptoms such as frequent urination or difficulty urinating.
• Assessment of Bowel Function: Invasion into nearby structures may affect bowel function, causing symptoms such as constipation or changes in bowel habits.

Evaluation of Systemic Symptoms:

• General Well-being: The healthcare provider assesses the patient’s overall health and looks for signs of systemic symptoms such as weight loss, fatigue, or signs of anemia.

Surgery:

• Conization or Loop Electrosurgical Excision Procedure (LEEP): In cases of early-stage cervical cancer or precancerous lesions, a small cone-shaped piece of tissue containing the abnormal cells may be removed.
• Hysterectomy: Removal of the uterus can be recommended for more advanced cases or when conservative approaches are not feasible.
• Pelvic Lymph Node Dissection: If the cancer has spread, lymph nodes in the pelvis may be removed to check for metastasis.

Radiation Therapy:

• External Beam Radiation: High-energy beams are directed at the pelvic region to target cancer cells.
• Brachytherapy:A stronger radiation dose is applied by inserting radioactive sources inside or close to the tumor. This is often used in combination with external beam radiation.

Chemotherapy:

• Systemic Chemotherapy: Intravenous drug administration is used to aim at cancer cells all over the body. For some stages, radiation therapy and chemotherapy can be used separately or in conjunction.

Combined Modality Therapy:

• Concurrent Chemoradiation: Concurrent chemotherapy and radiation therapy are administered to maximize treatment efficacy.

Targeted Therapies:

• Bevacizumab: An anti-angiogenesis medication that can be combined with chemotherapy to prevent blood vessel creation in advanced cervical cancer tumors.

Immunotherapy:

• Pembrolizumab: A PD-1 inhibitor that has shown effectiveness in some cases of recurrent or metastatic cervical cancer.

Clinical Trials:

• It may be thought of taking part in clinical trials to investigate novel medication combinations and treatment modalities, particularly in situations that are advanced or recurrent.

Nutrition

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Oncology, Radiation

Nutritional Support: A healthy, well-balanced diet is important for general well-being and can help the body fight cancer. Proper nutrition can help maintain strength, energy levels, and immune function.

Physical Activity: Regular exercise, within the limits set by the healthcare team, can contribute to physical well-being and help manage treatment-related side effects, such as fatigue. Strength, flexibility, and cardiovascular fitness exercises could be helpful.

Psychosocial Support: Emotional and psychological well-being is crucial during cancer treatment. Supportive groups, psychotherapy, or counseling can assist people in overcoming the emotional difficulties brought on by a cancer diagnosis.

Mind-Body Techniques: Techniques such as meditation, mindfulness, and relaxation exercises may assist in managing stress, anxiety, and improving overall quality of life. These practices can be beneficial for both the patient and their caregivers.

Acupuncture and Massage Therapy: Acupuncture may help alleviate certain symptoms, such as pain and nausea, and provide relaxation. Massage therapy can contribute to stress reduction, improve circulation, and enhance well-being.

Physical Therapy: Physical therapy may be beneficial, especially after surgery, to aid in recovery, improve mobility, and address any functional limitations.

Fertility Preservation Counseling: Non-pharmacological methods for younger individuals who are interested in maintaining fertility could involve talking about freezing eggs or embryos before receiving certain cancer therapies.

Educational Support: Providing educational tools and support to patients and their families can enable them to actively engage in their care by helping them understand the evaluation, treatment, choices, and potential side effects.

Spiritual Care: Spiritual support, whether through religious practices or spiritual counseling, can be an important component of holistic care, offering comfort and guidance to individuals facing a cancer diagnosis.

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5-fluorouracil (5-FU) is a chemotherapy drug that has been used in the treatment of various cancers, including cervical carcinoma. While 5-FU is not typically a first-line treatment for cervical cancer, it may be part of combination chemotherapy regimens, especially in cases of advanced or metastatic disease.

Combination Chemotherapy:

• 5-FU is often used in combination with other chemotherapy drugs to enhance its effectiveness.
• Combinations may include drugs like cisplatin, paclitaxel, or other agents, depending on the specific treatment plan designed by oncologists.
• These combinations are tailored to target different aspects of cancer cell growth and division.

Locally Advanced Cervical Cancer:

• In cases of locally advanced cervical cancer, where the tumor is extensive but has not yet spread to distant organs, combination chemotherapy regimens that include 5-FU may be considered.
• Chemotherapy may be administered before surgery (neoadjuvant), after surgery (adjuvant), or concurrently with radiation therapy.

Metastatic or Recurrent Cervical Cancer:

• 5-FU may be included in systemic chemotherapy regimens for cervical cancer patients whose cancer has recurred or metastasized to other organs.
• The goal is to control the growth of cancer cells throughout the body.

Mode of Action:

• 5-FU is a kind of antimetabolite that messes with DNA and RNA synthesis, which stops cell division and DNA replication.
• By inhibiting the production of essential nucleotides, 5-FU can induce cell death in rapidly dividing cancer cells.

Combination with Radiation:

• In some cases, 5-FU may be used in combination with radiation therapy, enhancing the radiation’s effectiveness as a radiosensitizer.

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Chemotherapy is a key component of cervical carcinoma treatment, particularly when the cancer has metastasized outside of the cervix or when recurrence risk is high. 

Neoadjuvant Chemotherapy: It is administered before the primary treatment, often surgery or radiation therapy. It aims to shrink the tumor, making it more amenable to surgical removal or radiation. 

Concurrent Chemotherapy and Radiation: In cases of locally advanced cervical cancer (Stage IIB and beyond), chemotherapy is often given concurrently with radiation therapy. Cisplatin is a common chemotherapy drug used concurrently with radiation as a radiosensitizer. This combined approach, known as chemoradiation, enhances the effectiveness of both treatments. 

Adjuvant Chemotherapy: It is administered following the original therapy to kill any leftover cancer cells and limit the likelihood of recurrence. When there is a high chance of recurrence due to elements like positive surgical margins or lymph nodes, it is frequently taken into consideration. 

Carboplatin: 

• Carboplatin is a platinum-based chemotherapy drug that works by damaging the DNA inside cancer cells, preventing them from dividing and growing. 
• It is often used in combination with other chemotherapy drugs, such as paclitaxel or gemcitabine, for the treatment of advanced or recurrent cervical cancer. 
• It is administered intravenously and is generally well-tolerated, although it can cause side effects such as nausea, vomiting, hair loss, and bone marrow suppression. 

Gemcitabine: 

• Gemcitabine is a nucleoside analog chemotherapy drug that disrupts the replication of cancer cells by interfering with DNA synthesis. 
• It is commonly used in combination with other chemotherapy agents for the treatment of advanced or metastatic cervical cancer. 
• It is administered intravenously and may cause side effects such as flu-like symptoms, nausea, vomiting, and low blood cell counts. 

Ifosfamide: 

• Ifosfamide is an alkylating agent chemotherapy drug that works by damaging the DNA in cancer cells, preventing them from dividing and growing. 
• It is used as part of combination chemotherapy regimens for the treatment of advanced or recurrent cervical cancer. 
• It is administered intravenously and can cause side effects such as nausea, vomiting, hair loss, and bone marrow suppression. It may also cause bladder toxicity, which can be minimized with adequate hydration and the use of mesna. 

Irinotecan: 

• Irinotecan is a topoisomerase inhibitor chemotherapy drug that interferes with the DNA replication process in cancer cells, leading to cell death. 

• It is sometimes used as a second-line treatment for advanced or metastatic cervical cancer that has progressed despite initial chemotherapy. 
• It is administered intravenously and may cause side effects such as diarrhea, nausea, vomiting, fatigue, and low blood cell counts. 

Vinorelbine: 

• Vinorelbine is a vinca alkaloid chemotherapy drug that disrupts the formation of microtubules in cancer cells, preventing them from dividing and proliferating. 
• It may be used as part of combination chemotherapy regimens for the treatment of advanced or metastatic cervical cancer. 
• It is administered intravenously or orally and can cause side effects such as nausea, vomiting, constipation, fatigue, and low blood cell counts. 

Cisplatin: 

• Cisplatin is a platinum-based chemotherapy drug that works by damaging the DNA in cancer cells, which ultimately leads to cell death. 
• It is a cornerstone of treatment for cervical cancer and is often used in combination with other chemotherapy agents, such as paclitaxel or topotecan. 
• It is typically administered intravenously and is commonly used in both the definitive (primary) treatment and in the management of recurrent or metastatic cervical cancer. 
• Side effects of cisplatin may include nausea, vomiting, kidney damage (nephrotoxicity), nerve damage (neurotoxicity), hearing loss, and bone marrow suppression. 

Paclitaxel: 

• Paclitaxel is a taxane chemotherapy drug that works by interfering with the normal function of microtubules, which are essential for cell division and growth. 
• It is often used in combination with cisplatin or other chemotherapy agents for the treatment of cervical cancer, particularly in advanced or metastatic cases. 
• It is administered intravenously and may cause side effects such as nausea, vomiting, hair loss, peripheral neuropathy, and bone marrow suppression. 

Topotecan: 

• Topotecan is a topoisomerase inhibitor chemotherapy drug that interferes with DNA replication and repair in cancer cells, leading to cell death. 
• It is commonly used as a second-line treatment for recurrent or metastatic cervical cancer that has progressed despite initial chemotherapy. 
• It is administered intravenously or orally and may cause side effects such as nausea, vomiting, diarrhea, fatigue, and bone marrow suppression. 

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Cervical Conization:

• A cone-shaped piece of tissue which is abnormal is removed from the cervix during what is also referred to as a cone biopsy.
• It is often performed to diagnose and treat precancerous lesions (such as cervical intraepithelial neoplasia, or CIN) or early-stage cervical cancer.
• Cervical conization may be performed using various techniques, including loop electrosurgical excision procedure (LEEP) or cold knife conization.

Lymph Node Dissection:

• The surgical excision of pelvic lymph nodes is referred to as lymph node dissection, or lymphadenectomy.
• It may be performed to assess the extent of lymph node involvement and to determine the stage of cervical cancer.
• Lymph node dissection is often performed during radical hysterectomy or pelvic exenteration procedures.

Percutaneous Radiologic Interventions:

• Interventional radiologic procedures may be used for the palliative treatment of cervical cancer metastases, such as those involving the liver, lungs, or bones.
• Techniques include percutaneous ablation (radiofrequency ablation, microwave ablation) to destroy tumor tissue and embolization to block blood flow to tumors (transarterial chemoembolization or selective internal radiation therapy).

Percutaneous Drainage and Stenting:

• In cases where cervical cancer causes obstructive complications, such as hydronephrosis due to ureteral obstruction, percutaneous drainage procedures may be performed to relieve symptoms and improve quality of life.
• Placement of ureteral stents or nephrostomy tubes can help bypass obstructed areas and restore normal urine flow.

Brachytherapy:

• In this type of internal radiation therapy, radioactive sources are positioned inside or close to the tumor.
• It is a crucial treatment for cervical cancer, especially when it comes to giving the tumor significant radiation doses without harming the nearby healthy tissues.

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Preventive Phase:

• Screening and Early Detection: Regular Pap smears (Pap tests) and HPV (human papillomavirus) testing are crucial for early detection of precancerous changes or cervical cancer.Timely intervention and better treatment outcomes are made possible by early identification.

Diagnostic Phase:

• Biopsy: Cervical cancer is confirmed to be present and its type and stage are determined by a biopsy if abnormalities are found during screening. This phase helps establish the baseline for further treatment planning.

Staging Phase:

• Clinical and Imaging Staging: Staging involves determining the extent of cancer spread. Imaging studies (such as CT scans, MRI, or PET scans) and clinical assessments help classify the cancer stage (from I to IV) based on the size of the lymph node involvement,tumor and presence of metastasis.

Treatment Planning Phase:

• Multidisciplinary Consultation: A team of specialists, including gynecologic oncologists, radiation oncologists, medical oncologists, and other healthcare professionals, collaborates to create an individualized treatment plan based on the cancer’s characteristics and the patient’s overall health.

Primary Treatment Phase:

• Surgery: Surgical interventions, such as radical hysterectomy (removal of the uterus, cervix, and surrounding tissues) or pelvic exenteration, may be recommended for localized cervical cancer.
• Radiation Therapy: External beam radiation therapy (EBRT) and/or brachytherapy may be employed to deliver targeted radiation to the affected area, aiming to destroy cancer cells.
• Chemotherapy:  Chemotherapy may be used alone or in combination with other treatments. Cisplatin is a common chemotherapy drug used in cervical cancer treatment.

Adjuvant Therapy Phase:

• Adjuvant Chemotherapy:To target any cancer cells that may still be present after surgery and lower the chance of recurrence, further chemotherapy may be suggested.
• Adjuvant Radiation: In some cases, radiation therapy may be administered after surgery to eliminate residual cancer cells.

Maintenance and Surveillance Phase:

• Follow-Up Care: Patients have follow-up sessions on a regular basis after finishing main therapy in order to track their progress and look for any indications of recurrence.
• HPV Vaccination: In order to lower the likelihood of cervical cancer and prevent further infections, vaccination for high-risk HPV strains may be advised for suitable candidates.

Palliative Care Phase:

• Palliative Interventions: Palliative interventions may include pain management, supportive care, and procedures to alleviate obstructive complications.