Cervical Cancer Guide

Anatomy of the Female Reproductive Organs 

The internal reproductive organs in women include:

• Cervix - the narrow end of the uterus forming a canal between the uterus and the vagina.
• Vagina - an expandable, muscular canal that is a vital part of female reproductive anatomy.
• Uterus - a hollow muscular organ located in the female pelvis between the bladder and the rectum.
• Fallopian Tubes - a pair of tubes in the human body that extend from the uterus to the ovaries.
• Ovaries - small glandular organs located on either side of the uterus at the ends of the Fallopian tubes.

About Cervical Cancer 

Cervical cancer occurs when cells in the cervix, which connects the uterus and the vagina, change. This cancer can affect the deeper tissues of the cervix and spread to other parts of the body (metastasis), often to the lungs, liver, urinary bladder, vagina, and rectum. Cervical cancer develops slowly, so there is usually time to detect and treat it before it causes serious problems. 

One of the most important measures for early detection of the disease is regular PAP tests. In Bulgaria, there is a constantly increasing incidence of the disease – annually, between 1100 and 1200 new cases are registered among women, with death cases ranging from 300 to 400 annually. This means that every day in the country, one woman dies from cervical cancer, and three new cases of the disease are diagnosed. Globally, cervical cancer is the fourth most common cancer among women according to the WHO.

Types of Cervical Cancer

Cervical cancer can be classified differently based on the type, stage of development, and spread of the abnormal cells. There are three known types of cervical cancer according to the structure of the tumor cells:

• Squamous Cell Tumors: This is the most common subtype, accounting for 70%-80% of cases of cervical carcinoma. Squamous cell carcinoma begins in the thin, flat cells that cover the cervix.
• Glandular Tumors (Adenocarcinoma): This subtype accounts for 20%-25% of cervical cancer cases. Adenocarcinoma begins in the cells of the cervix that produce mucus and other fluids.
• Other Epithelial Tumors: These rarer subtypes include adenosquamous carcinoma, neuroendocrine tumors, and undifferentiated carcinoma.

Cervical cancer is also classified according to how advanced the disease is:

Noninvasive Cervical Intraepithelial Neoplasia 

Cervical intraepithelial neoplasia (CIN) is a term used to describe abnormal changes in the squamous cells of the cervix. This is not cancer, but it can progress to cancer in the future. CIN is categorized into three grades:

• CIN 1: Up to one-third of the thickness of the mucosa covering the cervix has abnormal cells.
• CIN 2: Between one-third and two-thirds of the mucosa covering the cervix has abnormal cells.
• CIN 3: The entire thickness of the mucosa covering the cervix is covered with abnormal cells. Cell changes in CIN 1 often normalize over time, and most patients do not require treatment. In patients with CIN 2 and CIN 3, treatment may be applied to remove the abnormal cells to prevent them from progressing to invasive cervical cancer.

Depending on the location and extent of spread, cervical cancer can be:

• Early Cervical Cancer: Cervical cancer is considered early if the tumor has not spread beyond the cervix. These types of cancer can usually be operated on, and the main treatment is surgery to remove the cancer.
• Locally Advanced Cervical Cancer: Cervical cancer is locally advanced if it has spread beyond the cervix into the surrounding tissues. Treatment for locally advanced cervical cancer usually starts with chemotherapy, but surgery may be performed if the tumor shrinks after neoadjuvant (preoperative) treatment.
• Metastatic Cervical Cancer: Cervical cancer is considered metastatic when it has spread to other parts of the body, such as the lungs. Tumors at distant sites are called metastases. Metastatic cervical cancer is not completely curable but can be treated.

Symptoms of cervical cancer

Cervical cancer often does not cause any symptoms or signs in its precancerous stages. Symptoms usually appear in the early stages of cervical cancer. In advanced cervical cancer, which has spread to other parts of the body, symptoms can be more severe depending on the tissues and organs affected.

Symptoms are changes you might feel in your body as the disease develops. Signs, on the other hand, are changes in something specific measured, such as your blood pressure measurement or a lab test. Together, symptoms and signs can help describe a medical problem. The cause of a symptom or sign can also be a medical condition that is not cancer, which is why people should seek medical help if they have a new symptom or sign that does not go away.

Any of the following could be a symptom or sign of cervical cancer:

• Spotting or light bleeding between or following periods.
• Menstrual bleeding that is longer and heavier than usual.
• Bleeding after intercourse or a pelvic exam.
• Increased vaginal discharge.
• Pain during sexual intercourse.
• Bleeding after menopause.
• Unexplained, persistent pain in the pelvis and/or back. Each of these symptoms should be reported to your doctor. If you experience these symptoms, it's important to discuss them with him or her, even if they seem like symptoms of other, less serious conditions.

Remember, the earlier precancerous cells or cervical cancer is detected and treated, the greater the chance of preventing/curing the cancer.

If you are concerned about any changes you are experiencing in your body, you must talk to your doctor and not delay the examination. Your doctor will try to understand what is causing your symptoms and will assign tests to find out the reasons for the condition. This is called making a diagnosis.

Cervical Cancer Screening 

Screening means checking for disease in a group of people who show no symptoms of the disease. Screening tests help to detect cervical cancer before symptoms develop. When cervical cancer is detected and treated on time, the chances of successful treatment are much better.

If you are already sexually active, you should start doing regular PAP tests (pap smear). Recommendations for the frequency of PAP tests are every 1 to 3 years, depending on your previous test results.

Risk Factors for Cervical Cancer A risk factor can be anything that increases a person's chance of developing cancer. While risk factors often influence the development of cancer, most do not directly cause cancer. Some people with multiple risk factors never develop cancer, while others with no known risk factors do. Knowing your risk factors and talking about them with your doctor can help you make more informed lifestyle and healthcare choices.

The following factors can increase the risk of developing cervical cancer:

• Infection with the human papillomavirus (HPV). The most important risk factor for cervical cancer is HPV. HPV is actually a common infection. Most infections occur after people become sexually active, and most people clear the virus without problems. There are over 100 different types of HPV. Not all of them are associated with cancer. The types or strains of HPV most commonly associated with cervical cancer are HPV16 and HPV18. Starting sexual life at an earlier age or having multiple sexual partners exposes a person to a higher risk of contracting high-risk types of HPV. HPV vaccines can prevent the development of some types of cancer, including cervical cancer.
• Immune system deficiency. People with a reduced immune system function are at a higher risk of developing cervical cancer. Reduced immune function can be caused by immunosuppression from corticosteroid medications, organ transplantation, treatments for other types of cancer, or by the human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). When a person has HIV, their immune system is less able to fight the early stages of cancer.
• Herpes. People with genital herpes are at a higher risk of developing cervical cancer.
• Smoking. Women who smoke are about twice as likely to develop cervical cancer compared to women who don't smoke.
• Age. Women under the age of 20 rarely develop cervical cancer. The risk increases between the late teens and mid-30s. Women after this age group remain at risk and should undergo regular cervical cancer screenings, which include a Pap test and/or HPV test.
• Socio-economic factors. Cervical cancer is more common among women who are less likely to have access to cervical cancer screening. These populations are more likely to include black women, Hispanics, American Indians, and women from low-income households.
• Oral contraceptives. Some studies show that oral contraceptives, which are birth control pills, may be associated with an increased risk of cervical cancer and may be associated with riskier sexual behavior. However, more research is needed to understand how the use of oral contraceptives and the development of cervical cancer are related.

Staging of cervical cancer

Staging is a method used to describe where the cancer is located, whether and where it has spread, and whether it affects other parts of the body.

Doctors use diagnostic tests and physical examinations to determine the cancer's stage, so staging may not be complete until all tests are finished. Knowing the stage helps the doctor recommend the best type of treatment and can help predict the patient's prognosis, which is the chance of recovery. There are different descriptions of stages for different types of cancer. For cervical cancer, the staging system developed by the International Federation of Gynecology and Obstetrics (Federation Internationale de Gynecologie et d'Obstetrique or FIGO) is used.

Important: Stage 0 is not included in the FIGO system. Stage 0 is a precancerous condition of the cervix, also called carcinoma in situ.

The various stages of cervical cancer according to FIGO are described as follows: FIGO STAGE I: Tumor confined to the cervix (T1-any N-M0) IA Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of 5 mm, measured from the base of the epithelium, and horizontal spread < 7 mm

• IA1: Measured stromal invasion with a depth <3 mm and horizontal spread <7 mm
• IA2: Measured stromal invasion >3 mm and <5 mm with horizontal spread <7 mm IB Clinically visible lesion confined to the cervix, or microscopic lesion larger than IA2
• IB1: Clinically visible lesion with the largest size <4 cm
• IB2: Clinically visible lesion with the largest size >4 cm

FIGO STAGE II: The tumor extends beyond the uterus but not into the pelvic wall or the lower third of the vagina (T2-any NM0) IIA Tumor without invasion into the parametrium IIA1: Clinically visible lesion with the largest size < 4 cm IIA2: Clinically visible lesion with the largest size >4 cm IIB Tumor with parametrial invasion

FIGO STAGE III: The tumor encompasses the lower third of the vagina or extends to the pelvic wall, or causes hydronephrosis or non-functioning kidney (T3-any N-M0) IIIA The tumor encompasses the lower third of the vagina IIIB The tumor extends to the pelvic wall or causes hydronephrosis or non-functioning kidney

FIGO STAGE IV. The tumor extends beyond the pelvis or clinically affects the mucosa of the bladder and/or rectum (T4-any N-M0 or any T-any N-M1)

Recurrent Cancer Recurrent cancer reappears after the initial treatment. Cervical cancer can recur in the pelvis where it started or spread to other areas of the body, such as the lungs, lymph nodes, and bones. If the cancer returns, new tests are conducted to determine the extent of the recurrence.

Diagnosis of cervical cancer 

Usually, the diagnosis of cervical cancer begins when a PAP test (Pap smear) shows an unusual result. Your doctor will ask about any symptoms you have and may perform a physical examination. Based on this information, your doctor will refer you to a specialist or order tests for cervical cancer or other health problems. It is normal to be concerned, but try to remember that other health conditions can cause symptoms similar to those of cervical cancer. It is important for the health team to rule out other causes of a health problem before a diagnosis of cervical cancer is made. The following tests are usually used to rule out or diagnose cervical cancer. Many of the same tests used for diagnosis are used to determine the stage (how far the cancer has spread). 

Medical history and physical examination 

Your medical history is a record of your symptoms, risk factors, and all the medical events and problems you have had in the past. This can also be called a patient file, which stores information about all examinations, treatments, allergies, hospitalizations, and other important health information. Your doctor will ask you questions regarding: 

• Symptoms suggesting cervical cancer 
• Sexual activity 
• Unusual results from a PAP test 
• Smoking 

The physical examination allows your doctor to detect and confirm signs of cervical cancer. During a physical examination, your doctor may: 

• Order a PAP test (Pap smear) and pelvic examination (colposcopy, ultrasound, MRI), as well as a liquid-based cytological test, often called ThinPrep or SurePath. These tests can serve as the earliest prognostic marker for cervical cancer and have high specificity and sensitivity compared to the regular PAP test. 
• Order a cone biopsy (conization): This is used for diagnosing cervical cancer and treating abnormal cells on the cervix. During a cone biopsy, a cone-shaped piece of tissue is removed from the cervix under general anesthesia. The sample is examined under a microscope to check for cancer cells or to see if all abnormal cells have been removed. 
• Perform an examination of the lymph nodes in the groin and above the clavicle.

More about each of these methods can be found in the following lines. 

PAP test 

The PAP test takes a small sample of cells from the surface of the cervix. Doctors examine the cells under a microscope to see if they look normal or unusual. The test can detect unusual changes in cells early, before cancer develops. 

The PAP test is used to screen for cervical cancer. It is performed every 1 to 3 years, depending on the screening guidelines in the country and your health history. Regarding the Pap smear, to ensure the result is as accurate and objective as possible, it is recommended to avoid sexual contacts, as well as the use of vaginal douches, tampons, and vaginal preparations at least two days before the test. 

The application of cytological screening as a preventive method can lead to inaccurate results in a small percentage of cases, as no research method is 100% accurate. Deviations may include: 

• False positive results - test results show abnormal changes in cells, but further testing reveals no pathology. 
• False negative results - in this case, the results do not detect precancerous cells. Statistics show that false-negative results are present in 5 to 25% of patients with such pathologies. 

The reasons for such incorrect results may be technological - regarding the collection of material, its contamination, and others. However, these deviations are practically eliminated if regular cytological screenings are conducted. 

Regarding the results, they are classified as follows: 

• PAP I – normal cells; 
• PAP II – data for inflammatory changes or benign changes (metaplasia), HPV infection; 
• PAP III – presence of atypical cells and recording the result as borderline. Here are two options, pointing to inflammation or degenerative process or dysplasia: data for severe dysplasia and registration of individual cancer cells; or registration of numerous cancer cells, indicating invasive carcinoma.

HPV Test

The test for human papillomavirus (HPV) is a laboratory test that searches for the DNA of only high-risk types of HPV, which are associated with cervical cancer. In some cases, the HPV test can be done on the same sample of cells collected during a PAP test.

Colposcopy

Colposcopy is a method where a colposcope (a lighted magnifying instrument) is used to examine the vulva, vagina, and cervix.

Colposcopy is performed after an abnormal result from a PAP test or a positive HPV test suggests a precancerous condition of the cervix or cervical cancer. Colposcopy can also be done if you have symptoms of cervical cancer.

Colposcopy is performed almost in the same way as the PAP test. The doctor inserts a speculum into the vagina. The speculum is a plastic or metal device that separates the walls of the vagina so that the doctor can clearly see the cervix. The doctor may apply a solution that helps the mucosa of the cervix show up better. Then, the doctor uses a colposcope to carefully examine the inner surface of the cervix and vagina. The colposcope is placed outside the vaginal opening and is not inserted into the vagina. The doctor may perform a biopsy during colposcopy if there are unusual symptoms or changes in the cervix.

Biopsy

If the PAP test shows unusual results, your doctor will likely need to take a biopsy from the cervix. During a biopsy, the doctor removes tissues or cells from the body so that they can be examined under a microscope to see if there are cancer cells in the sample.

The following biopsies can be used to take samples from cells and tissues from the cervix or nearby areas. Learn more about biopsy:

• During colposcopy, a colposcopic biopsy is done. A local anesthetic may be used to numb the cervix. The doctor uses biopsy forceps to remove small amounts of tissue from suspicious-looking areas in the cervix or vagina.
• During colposcopy, endocervical curettage is performed. A local anesthetic may be used to numb the cervix. The doctor uses a curette to carefully scrape cells and tissues from the endocervical canal. The curette is a narrow instrument shaped like a spoon.
• Endometrial biopsy uses a special instrument called a pipelle to remove cells from the lining of the inside of the uterus (called the endometrium), so they can be examined under a microscope to check for cancer. It can be done during colposcopy.
• A conical biopsy removes a cone-shaped piece of tissue from the cervix. The cone is formed by removing the outer part of the cervix closest to the vagina and part of the endocervical canal.
• Sentinel lymph node biopsy (SLNB) removes a sentinel lymph node to determine if cancer is present there. The sentinel lymph node is the first in a chain or cluster of lymph nodes that receives lymph fluid from the area around the tumor. If cancer cells spread, they are most likely to spread to these lymph nodes first. There may be more than one sentinel node depending on the drainage path of the lymph vessels around the tumor.

Complete Blood Count (CBC)

A complete blood count measures the number and quality of white blood cells, red blood cells, and platelets. It can be done to check for anemia from long-term or chronic vaginal bleeding. The complete blood count also gives doctors a baseline for comparing future blood tests during and after treatment.

Blood Chemistry Tests (Biochemistry)

Blood chemistry tests measure the levels of certain chemicals in the blood. They show how well certain organs are functioning and can help detect abnormalities.

Blood chemistry tests are done to check how well the kidneys and liver are functioning as part of the diagnostic process for cervical cancer. They also help determine whether these organs are healthy enough to cope with and recover from the effects of cancer treatment.

Endoscopy

Endoscopy allows the doctor to look inside the body cavities using a flexible tube with a light and lens at the end (called an endoscope).

Cystoscopy uses an endoscope (called a cystoscope) to examine the bladder and urethra. It is done to determine if the cancer has spread to these organs. Doctors may perform a biopsy simultaneously with cystoscopy if they find a suspicious area during the examination.

Sigmoidoscopy uses an endoscope (called a sigmoidoscope) to examine the sigmoid colon (the last part of the colon) and rectum. It is done to determine if the cancer has spread to the rectum. Doctors may perform a biopsy simultaneously with sigmoidoscopy if they find a suspicious area during the examination.

Chest X-Ray

X-rays use small doses of radiation to create images of parts of the body on film. A chest x-ray is used to see if the cancer has spread to the lungs.

Barium Enema

A barium enema is an X-ray test that uses a special dye (contrast material) called barium sulfate. It is used to check if cancer has spread to the colon or rectum.

Computed Tomography

Computed tomography uses special X-ray equipment to make 3D and cross-sectional images of organs, tissues, bones, and blood vessels in the body. The computer converts the images into detailed pictures.

Computed tomography is used to:

- Assess the condition of the pelvis, abdomen, and lymph nodes around the cervix.

- Evaluate whether cancer has spread to other organs or tissues.

- Make a more precise biopsy.

Nuclear Magnetic Resonance (MRI)

Nuclear magnetic resonance (MRI) uses powerful magnetic forces and radiofrequency waves to make cross-sectional images of organs, tissues, bones, and blood vessels. A computer converts the images into 3D pictures.

MRI is used to:

- Assess the pelvis, abdomen, and lymph nodes around the cervix.

- Evaluate whether cancer has spread to other organs or tissues.

- Make a more precise biopsy.

Intravenous Pyelogram (IVP)

An intravenous pyelogram (IVP) is a special X-ray picture of the urinary system. It may be used to see if cancer is blocking the ureters (tubes that connect the kidneys to the bladder). An intravenous pyelogram may not be necessary if computed tomography or MRI has been performed.

Positron Emission Tomography (PET Scanner)

Positron emission tomography (PET) uses radioactive materials called radiopharmaceuticals to look for changes in the metabolic activity of body tissues. A computer analyzes the radioactive patterns and creates 3D color images of the area being scanned. It may be combined with computed tomography, called a PET-CT scan.

Positron emission tomography can be used to detect cervical cancer that has recurred (recurrent cancer) or has spread to other organs or tissues (metastatic cancer).

Methods for Early Detection of Cervical Cancer

All women, especially those aged 30-49, should undergo a gynecological exam and test to determine if they have a precancerous condition of the cervix or if there is a high risk of development due to HPV infection.

Currently, three different tests are available for early detection of cervical cancer: HPV test, PAP (Papanicolaou) test, and acetic acid test. The type of test used may vary by country according to national guidelines, with PAP and HPV tests most commonly applied in Bulgaria.

If test results are unusual, this may mean there are changes in the cervix or precancerous cells are present. Recommended actions for women with abnormal results usually include undergoing a colposcopy, with or without a biopsy.

How are precancerous changes in the cervix treated?

Treatment of precancerous cervical cells involves destroying the abnormal cells in the cervix. This is usually done by freezing the cells (cryotherapy) or by removing the cells (LEEP or other methods).

Cryotherapy is a process of freezing and destroying the abnormal cells on the cervix. It involves applying cooled gas through a metal probe directly onto the cervix. This procedure only takes a few minutes. It usually does not cause pain for women, although it may cause some discomfort, cramps, and lead to vaginal discharge after the procedure. Medical specialists will specify the care that women should follow after treatment with cryotherapy. The follow-up visit is typically 6-12 months after treatment.

The loop electrosurgical excision procedure (LEEP) is a minimally invasive electrosurgical method for removing abnormal cells from the cervix, using a thin metal loop heated by electricity. The procedure is performed by medical personnel under local anesthesia. It takes only 20-30 minutes and may cause cramps or light to moderate bleeding.

It is important to note that LEEP is contraindicated in cases of active inflammatory processes of the female genitals. LEEP is also not recommended during pregnancy.

What should I do if I need more treatment?

After treatment, your doctor will schedule follow-up appointments. During these meetings, a clinical exam is usually performed, including an examination of the pelvic and rectal areas. Some patients may also have a computed tomography or PET/CT - your doctor will discuss this with you. Your doctor will inform you how often you need to return for additional follow-up appointments, but the typical schedule for follow-up includes checks every 3-6 months for the first 2 years after treatment, every 6-12 months after 3 years, and annually after 5 years.

Despite the best possible treatment at diagnosis, there is still a chance that cancer can return. Cancer that comes back is called a recurrence. The treatment that will be offered to you depends on the extent of the recurrence. When the tumor returns as a recurrence at one location in the pelvis after primary surgery, radiation therapy or pelvic exenteration (removal of the bladder, part of the intestines, ovaries, uterus, cervix, and vagina) may be offered. Recurrent tumors in distant organs are considered metastatic cancer and chemotherapy and targeted therapy may be offered.

After treatment for cervical cancer, you may feel very exhausted and emotional. Give your body time to recover and make sure you rest enough, but there is no reason to limit your physical activity if you feel well. It is important to take good care of yourself and receive the support you need through good food, less stress, more rest time and with family, and physical activity.

Remission and the Likelihood of Recurrence

Remission is a condition where cancer cannot be detected in the body and there are no symptoms. This can also be called "no evidence of disease" or NED.

Remission can be temporary or permanent. This uncertainty makes many people worry that cancer will reappear. While many remissions are permanent, it's important to talk to your doctor about the possibility of cancer returning. An important part of follow-up care is monitoring for recurrence, which is done according to national health guidelines in the country.

If cancer reappears after initial treatment, it is called recurrent cancer. Recurrent cancer can occur again at the same site (called local recurrence), nearby (regional recurrence) or at another location (distant recurrence).

If a recurrence occurs, a new cycle of testing will begin to learn as much as possible about it. Once this evaluation is done, you and your doctor will discuss treatment options. The treatment plan may include the treatments described above, such as surgery, targeted therapy, and radiation therapy, but they may be used in a different combination or applied at a different pace.