Cervical Cancer

Cervical cancer is a type of cancer that occurs in women in the cells of their cervix. The cervix is the lower part of the uterus that connects to the vagina.

In the United States, almost 14,500 women are diagnosed with cervical cancer every year and more than 4000 will die from it. The incidence of cervical cancer has declined dramatically worldwide in those countries with access to cervical cancer screening (Pap tests/smears) and human papillomavirus vaccination (HPV). However, in less developed countries it continues to rank as one of the leading causes of cancer-related deaths among women. Virtually all cases of cervical cancer are associated with the HPV virus, with two strains, HPV 16 and HPV 18, estimated to cause up to 70% of all cases. Cervical cancer is one of the most preventable types of cancer.

What is cervical cancer?

The cervix is the narrow opening into the uterus from the vagina. Cervical cancer starts in the cells lining the cervix. The cervix has two main parts:

The exocervix (also called ectocervix) is the part next to the vagina. This is covered in thin, flat squamous cells

The endocervix is the part closest to the uterus. This is covered with glandular cells.

The area where these cells meet is called the transformation zone (T-zone). The exact location of this zone changes as you get older and after giving birth. The T-zone is the most likely location for abnormal or precancerous cells to develop.

80% to 90% of all cervical cancers are squamous cell cancers. The rest are adenocarcinomas which develop from the glands that produce mucus in the endocervix. The incidence of adenocarcinomas is rising, especially among younger women.

Cell changes happen very slowly in the cervix, and experts estimate it usually takes more than 10 years for cell changes to become cancer. 

What are the symptoms of cervical cancer?

Early-stage cervical cancer rarely has signs or symptoms. You might not notice anything wrong until you have a routine Pap test. 

Once cervical cells become cancerous, symptoms are more likely. Symptoms may include:

Abnormal vaginal bleeding

Increased vaginal discharge

Pain during sex

Bleeding years after menopause.

It is important to see your doctor if you develop any of the symptoms listed above. 

What are HPV tests and Pap tests (Pap smears) and why are they important?

HPV (human papillomavirus) is the most commonly sexually transmitted infection in the United States. You can become infected with HPV by having vaginal, anal, or oral sex with someone who has the virus.

There are over 100 different types of HPV and certain types, mainly HPV 16 and HPV 18, cause 70% of cervical cancers and pre-cancerous cervical lesions. HPV infection is also associated with cancers of the anus, vulva, vagina, penis, and oropharynx. 

The most important risk factor for developing cervical cancer is infection with HPV.

HPV tests are currently done with a vaginal swab, although a urine test for HPV that can be done at home is under development. An HPV DNA test can be carried out using the same swab taken from the Pap tests. A primary HPV test is a test that only looks for HPV (not precancerous or cancerous lesions).

Pap tests detect abnormal cells in and around the cervix. They are the only way to detect precancerous conditions (these are cell changes that have a high chance of developing into cancer) which rarely have any symptoms. Pap tests are simple and painless, although a small amount of discomfort may occur.

During a Pap test, a doctor uses a vaginal speculum to hold your vagina open, which allows him or her to properly examine your cervix and brush samples from your cervix to be examined later in a laboratory for abnormalities.

Co-testing consists of a Pap test plus an HPV test.

How often should I have an HPV and/or a Pap test?

Cervical cancer screening should begin in women with a cervix at age 25 according to the American Cancer Society. This includes women who have been vaccinated against HPV because the HPV vaccine does not protect you from all types of HPV. 

For women aged 25 to 65, the preferred method of screening is a primary HPV test. If a primary HPV test is not available, then screening may be done with a combined HPV test and Pap test every 5 years, or a Pap test alone every three years.

Those over the age of 65 who have had normal screening results over the past 10 years with no history of carcinoma in-situ or worse within the past 25 years should stop cervical cancer screening.

Co-testing or more frequent testing may be routinely advised in women who are HIV positive or who have been diagnosed or treated for cervical cancer or pre-cancer. Screening can also stop in women who have had a total hysterectomy (removal of the uterus and cervix).

Note that recommendations for screening vary between expert organizations. Some guidelines recommend against HPV screening in those under the age of 30. This is because HPV is common in young people and it frequently clears on its own within a year or two.

What are precancerous conditions?

Sometimes cells on the surface of the cervix can appear abnormal but not cancerous, but may, however, become cancerous over time. The abnormal cells are known as precancerous lesions or squamous intraepithelial lesions (SIL).

 Changes in these cells can be divided into two categories:

Low-grade SIL (LSIL) refers to early changes in the size, shape, and number of cells that form the surface of the cervix. Some low-grade lesions may disappear altogether, others can grow larger or become more abnormal, forming a high-grade lesion. Precancerous low-grade lesions may also be called mild dysplasia or cervical intraepithelial neoplasia 1 (CIN 1). These early changes in the cervix most often occur in women between the ages of 25 and 35 but can appear in other age groups as well.

High-grade SIL (HSIL) means there are a large number of precancerous cells. Like low-grade SIL, these precancerous changes involve only cells on the surface of the cervix. The cells do not become cancerous and invade deeper layers of the cervix for many months, perhaps years. High-grade lesions may also be called moderate or severe dysplasia, CIN 2 or 3, or carcinoma in situ. These changes in the cervix most often occur in women between the ages of 30 and 40 but can occur in other age groups as well.

If abnormal cells spread deeper into the cervix or to other tissues or organs, the disease is then called cervical cancer, or invasive cervical cancer. This occurs most often in women over the age of 40.

Understanding your test results

HPV testing

HPV test results show if high-risk HPV types were found in cervical cells. An HPV test will come back as a positive test result or a negative test result.

A negative HPV test result means that high-risk HPV was not found. You should repeat the test in 5 years, or more frequently if you have had abnormal results in the past.

A positive HPV test result means that you have a type of high-risk HPV that's linked to cervical cancer. This does not mean that you have cervical cancer now, but it is a warning that cervical cancer could develop in the future. More tests, such as a Pap test, colposcopy, or biopsy may be needed. Your health care provider will tell you what follow-up steps you need to take, based on your specific test result.   

HPV test results usually come back from the lab in about one to three weeks. If you don't hear from your health care provider, call and ask for your test results. 

Sometimes, after several negative HPV tests, a woman may have a positive HPV test result. For women with a new sexual partner, this is most likely a new infection. For women in a monogamous relationship, this does not necessarily mean that their partner has another sexual partner. Sometimes an HPV infection can become active again after many years and there is no way to tell whether a newly positive HPV test result is a sign of a new infection or a reactivation of an old infection. 

Pap Testing

90% of Pap test results are perfectly normal. The other 10% of results do not necessarily reflect cancer; there may be other reasons why they haven’t come back as normal. Here is an overview of what your Pap test results may show.

Normal

Unsatisfactory result. The sample taken from the cervix was insufficient to report on. Repeat the Pap test within 3 months

Inflammation or infection. The sample detected an infection. See your doctor for treatment.

Atypical cells. Mild atypical changes were detected (called ASC-US cells). If you are over 30 and HPV was also detected, then you may be referred to a specialist for a colposcopy. If you are under 30, the PAP test should be repeated in a year.

Mild (low-grade) changes (LSIL). Cells are beginning to change but it may take several years to become a problem. Often due to an HPV infection and it usually resolves itself. A referral to a specialist is usually made.

Moderate to severe (high-grade) changes (HSIL). A moderate to severe change is detected. A referral to a specialist is usually made to check it out.

Glandular cell changes or adenocarcinoma-in-situ (AIS). Sometimes cancer-like changes are detected. A referral for colposcopy is made, and it is important for you to go to your appointment.

Cancer. An immediate referral to a specialist is made. Early treatment is important.

How is cervical cancer diagnosed?

Following an abnormal Pap test result, the following diagnostic procedures may be performed before the diagnosis of cervical cancer is made.

Colposcopy: This is an instrument similar to a microscope that is used to view the cervix to look for abnormal areas.

Cervical biopsy: A small sample of cervical tissue is taken under local anesthetic for examination by a pathologist. This may be done using a loop electrosurgical excision procedure (LEEP) which uses a small loop of wire to remove the tissue.

Endocervical Curettage (ECC): This allows the specialist to see inside the opening of the cervix which cannot be seen during colposcopy. A curette (a small, spoon-shaped instrument) is used to take a sample of the cervix by scraping tissue from the cervical opening.

Cone Biopsy or Conization: A larger, cone-shaped sample of tissue is removed and examined by a pathologist to determine the thickness of abnormal cells. May also be used as a treatment for a precancerous lesion.

Dilation and Curettage (D and C): The cervical opening is stretched and tissue is scraped from the lining of the uterus as well as from the cervical canal.

How are precancerous cells treated?

Abnormal tissue may be removed from the cervix by several different procedures, such as cryosurgery (freezing), cauterization (burning, also called diathermy), or laser surgery.

Procedures used for biopsies, such as conization or LEEP procedures, may also be used.

Hysterectomy may be considered if abnormal cells are found inside the opening of the cervix and the woman does not intend to have children in the future.

How is cervical cancer treated?

Treatment for cervical cancer may involve surgery, radiation therapy, chemotherapy, targeted therapy, and/or immunotherapy. A combination of treatments is usually given, with the choice depending on the stage of cervical cancer, the size, and shape of the tumor, and individual patient factors (such as age, desire to have children, or other concurrent conditions).

The outlook for women with precancerous changes of the cervix or very early cancer of the cervix is excellent, and nearly all patients with these conditions can be cured. Researchers continue to look for new and better ways to treat invasive cervical cancer.

Surgery

Surgery involves removing the abnormal area of tissue from the cervix and procedures similar to those used to remove precancerous lesions may be used, for example, conization or hysterectomy, depending on the extent of cancer. After conization, patients may suffer cramping or other pain, bleeding, or a watery discharge after treatment. For a few days after a hysterectomy, pain and discomfort will usually need to be controlled with pain relievers and a catheter is inserted into the bladder to drain the urine.

Radiation therapy

Radiation therapy (radiotherapy) uses high-energy rays to damage cancer cells and stop them from growing. It only affects cancer cells in the treated area. The radiation may come from a large machine (external radiation) or radioactive materials placed directly into the cervix (internal or implant radiation). Some patients receive both types of radiation therapy.

Patients are likely to become very tired during radiation therapy, especially in the later weeks of treatment. With external radiation, it is common to lose hair in the treated area and for the skin to become red, dry, tender, and itchy. There may be permanent darkening or "bronzing" of the skin in the treated area. This area should be exposed to the air when possible but protected from the sun. Patients who receive external or internal radiation therapy also may have diarrhea and frequent, uncomfortable urination. The doctor can make suggestions or order medicines to control these problems.

Chemotherapy

Chemotherapy is the use of oral or injected drugs to kill cancer cells. Sometimes the chemotherapy may be placed directly into the area needing treatment (called regional chemotherapy). A single drug or a combination of drugs may be used. It is most often used when cervical cancer has spread to other parts of the body. Chemotherapy is usually given in cycles: a treatment period followed by a recovery period, then another treatment period, and so on.

Agents that may be used to treat cervical cancer include:

cisplatin (Platinol)

5-fluorouracil (Adrucil)

carboplatin (Paraplatin)

topotecan (Hycamtin)

ifosfamide (Ifex)

paclitaxel (Taxol)

gemcitabine (Gemzar, Infugem)

docetaxel (Taxotere)

irinotecan (Camptosar)

mitomycin.

The side effects of chemotherapy depend mainly on the specific drugs and the dose. In general, anticancer drugs affect rapidly dividing cells. These include blood cells, which fight infection, help the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected, patients are more likely to get infections, may bruise or bleed easily, and may feel unusually weak and very tired. Rapidly dividing cells into hair roots and cells that line the digestive tract may also be affected. As a result, side effects may include loss of hair, poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores.

Many of these side effects can now be controlled, thanks to new or improved drugs. Side effects generally are short-term and gradually go away. Hair grows back, but it may be different in color and texture.

Targeted treatments

Targeted treatments target specific changes in cancerous cells or in the tissues surrounding the cells. For example, angiogenesis inhibitors target new blood vessel growth needed to keep cancerous cells nourished.

Examples of targeted treatments used in the treatment of cervical cancer include:

•    bevacizumab (Avastin).

Common side effects include high blood pressure, tiredness, and loss of appetite.

Immunotherapy

Immunotherapy uses medicines to stimulate the body’s immune system to recognize and destroy cancer cells more effectively. Examples of immunotherapy treatments that can be used to treat cervical cancer include:

•  Immune checkpoint inhibitors: pembrolizumab (Keytruda)

These treatments may cause flu-like symptoms such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems.

Prevention of cervical cancer

At present, early detection and treatment of precancerous tissue remain the most effective ways of preventing cervical cancer. A Pap test with or without an HPV test is currently the best way to detect early cell changes that may lead to cervical cancer early. 

Gardasil 9 is a preventive vaccine against HPV. It is licensed for use in both males and females aged 9 through 45 to prevent cervical/vaginal/anal/penile cancers or genital warts caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It will not prevent diseases caused by other types of HPV.

The CDC recommends all children aged 11 to 12 years old (but may be given to those as young as 9 years) should get two shots of HPV vaccine six to twelve months apart. Those who receive their two shots less than five months apart will require a third dose of HPV vaccine at least four months after the second dose. Children, adolescents, or adults who are over 14 years or with certain immunocompromising conditions will require three shots which will need to be given over 6 months.

Gardasil 9 may be given even if you have already had genital warts, a positive HPV test, or an abnormal pap smear in the past; however, it will not treat active infections.