Treatment Update: Cervical Cancer

BOOKLET

Introduction

Thanks to major advances, healthcare providers can now prevent and treat cervical cancer more effectively.

Cervical cancer occurs in the cells of the cervix—the lower part of the uterus that connects to the vagina. It was once one of the most common cancers in women. In recent decades the incidence has decreased, as improved screening methods have made it easier for healthcare providers to find abnormal cells that can become cancerous.

Most cases of cervical cancer are caused by certain types of the human papillomavirus (HPV). In a small percentage of people exposed to HPV, the viral infection can persist for years and contribute to causing cervical cells to become cancerous.

There are two main types of cervical cancer:

Squamous cell carcinoma, which begins in the thin, flat cells (squamous cells) lining the outer part of the cervix. Approximately 70 percent of cervical cancers are squamous cell carcinomas.
Adenocarcinoma, which begins in the column-shaped glandular cells that line the endocervical canal (the passageway from inside the uterus to the vagina). Adenocarcinoma accounts for approximately 20 percent of cervical cancer cases.

Screening and Diagnosis

Cervical cancer is usually slow-growing and may not show any symptoms. Regular screening tests are very effective at detecting precancerous cells that may develop into cervical cancer.

Pap test. During a Pap test, cells are collected from the cervix and examined in a lab for abnormalities.
HPV DNA test. Cells collected from the cervix are tested to see if they are infected with any of the types of HPV that could lead to cervical cancer.

If cervical cancer is suspected after screening tests, a colposcope (magnifying instrument) is used to check if there are visual indications of the presence of abnormal or precancerous cells. Typically, a gentle scraping of the lower part of the cervical canal will be performed, in which samples of cervical cells are taken and looked at under a microscope by a pathologist. If a diagnosis of cervical cancer is made, further imaging and visual tests will be conducted to determine if the cancer has spread beyond the cervix.

Treatment Options

Treatment options depend on the type of cervical cancer, its stage, whether it is newly-diagnosed or recurrent (returned) and if the woman wants to preserve fertility.

Surgery

Early-stage (confined to the cervix) cervical cancer is usually treated with surgery. Surgical options include:

Cone biopsy. In this procedure, very small cervical cancers are removed entirely by cutting away a cone-shaped piece of cervical tissue. This leaves the rest of the cervix intact and allows for the possibility of a future pregnancy.
Radical trachelectomy. In this surgical approach, the cervix and some surrounding tissue is removed. The uterus remains intact, allowing for the possibility of a future pregnancy.
Total hysterectomy. In a total hysterectomy, the uterus and cervix are removed.
Radical hysterectomy. For cancer that has spread beyond the cervix, a radical hysterectomy is often performed. This surgery involves removing the cervix, uterus, part of the vagina and nearby lymph nodes.

Depending on your individual circumstances, your doctor might discuss the removal of the ovaries during either a total or radical hysterectomy. This procedure is called an oophorectomy.

Chemotherapy

Chemotherapy uses anti-cancer drugs that enter the bloodstream and kill cancer cells. It can be used to treat cervical cancer that has spread beyond the pelvis, recurs after treatment with surgery or after surgery in combination with chemoradiotherapy (see next section).

Cisplatin (Platinol, Platinol-AQ) is the chemotherapy most commonly used in combination with radiation for the treatment of locally advanced cervical cancer. This drug is given intravenously (as a drip into a vein). When the tumor has spread beyond the pelvis, paclitaxel (Taxol) is often administered.

Topotecan (Hycamtin and others) is usually given for the treatment of cervical cancer that is not responding to (or has stopped responding to) other types of therapy.

Radiation and Chemoradiotherapy

Radiation is the use of high-powered energy beams to kill cancer cells. For certain stages of cervical cancer, radiation is often given at the same time as the chemotherapy cisplatin, as it can make the radiation more effective. Radiation or chemoradiotherapy can also be given following surgery, and to treat cervical cancer that has spread or recurred after treatment.

Recent studies have shown that administering chemotherapy before chemoradiotherapy is effective in the treatment of locally advanced cervical cancer.

There are two types of radiation therapy used to treat cervical cancer:

External beam radiation (EBRT)

EBRT uses a machine to aim high-dose radiation at the cancer. The treatments are given several times a week over several weeks. The number of treatments is limited to avoid harming nearby tissues and organs.

Brachytherapy

Brachytherapy, also called internal radiation therapy, uses instruments which direct a source of radiation in or near the cancer. In intracavitary brachytherapy (the type most often used to treat cervical cancer), a device filled with radioactive material is placed in the vagina or the uterus. Brachytherapy is given on an outpatient basis over several treatments, usually at least a week apart.

When brachytherapy is used as a treatment for cervical cancer, it is usually in addition to EBRT and chemotherapy.

Targeted Therapy

Targeted therapies focus on specific molecules and cell mechanisms thought to be important for cancer cell survival and growth, taking advantage of what researchers have learned in recent years about how cancer cells grow. Targeted therapies are meant to spare healthy tissues and provide treatment against cancer cells that is more focused than chemotherapy. It may be a treatment option for later-stage cervical cancer.

Bevacizumab (Avastin) is a type of targeted therapy that “starves” tumors by blocking the action of VEGF (vascular endothelial growth factor), a protein released by tumors that contributes to blood vessel growth (angiogenesis). Bevacizumab is usually given with chemotherapy, as it makes the chemotherapy more effective.

Immunotherapy

Our immune system works constantly to keep us healthy. It recognizes and fights against danger, such as infections, viruses and growing cancer cells. In general terms, immunotherapy uses our own immune system as a treatment against cancer. It might be considered when the cervical cancer is advanced and other treatments aren’t working.

In 2021, the U.S. Food and Drug Administration (FDA) approved the immunotherapy pembrolizumab (Keytruda), with or without bevacizumab, for the treatment of recurrent or metastatic (advanced) cervical cancer with tumors that express a molecular “brake” known as PD-L1. The brake prevents the body’s immune system from attacking tumors. Pembrolizumab, which is designed to reverse the effect of the brake, is given intravenously.

In January 2024, the FDA approved pembrolizumab in combination with chemoradiotherapy for the treatment of FIGO 2014 Stage III-IVA cervical cancer, a type of squamous cell carcinoma.

Antibody-drug Conjugate

The FDA has approved tisotumab vedotin-tftv (Tivdak) for the treatment of recurrent or metastatic cervical cancer in people whose disease has progressed during or after chemotherapy. Tisotumab vedotin-tftv is an antibody-drug conjugate (ADC), a type of anticancer treatment that combines a targeted therapy with a chemotherapy drug.

Managing Treatment Side Effects

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all people experience all side effects, and people may experience side effects not listed here.

Side Effects of Chemotherapy

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:

Hair loss
Increased risk of infection (from having too few white blood cells)
Easy bruising or bleeding
Changes in memory or thinking
Peripheral neuropathy (numbness or tingling in hands and feet)

Side Effects of Radiation Therapy

Fatigue is the most common side effect of radiation. Additionally, changes to the skin can frequently occur. The changes can include dryness, swelling, peeling, redness and (rarely) blistering. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Side effects specific to EBRT in the treatment of cervical cancer include:

Irritation of the bladder. Called radiation cystitis, it can cause discomfort, an urge to urinate often and (sometimes) blood in the urine.
Vaginal pain. Radiation can make the vulva and vagina more sensitive.
Menstrual changes. The radiation can affect the ovaries, leading to menstrual changes and (in some cases) early menopause.
Low blood counts. Anemia (low levels of red blood cells) can cause fatigue. Neutropenia (low levels of white blood cells) increases the risk of infection. Thrombocytopenia (low levels of platelet counts) increases the risk of bleeding.

The most common side effect of brachytherapy in the treatment of cervical cancer is irritation of the vagina and vulva, with or without vaginal discharge.

Side Effects of Targeted Therapy

Targeted therapy doesn’t have the same effect on the body as do chemotherapy drugs, but it can still cause side effects. Side effects of targeted therapies can include diarrhea, liver problems (such as hepatitis and elevated liver enzymes), nerve damage, high blood pressure and problems with blood clotting and wound healing.

Side Effects of Immunotherapy

Immunotherapy travels through the bloodstream, helping to prompt an immune response. Because it can trigger an attack on healthy cells as well as cancer cells, certain side effects may be experienced, including fatigue, muscle pain, fever, cough, lowered levels of thyroid hormone, decreased appetite and digestive tract symptoms.

Side Effects of Antibody-drug Conjugate

The antibody drug conjugate used in the treatment of cervical cancer may cause nosebleeds, tiredness, muscle/joint pain, weight loss, vision changes, digestive tract symptoms and temporary hair loss.

FAQ's

Q: What are the risk factors for cervical cancer?

A: Factors that increase the risk of cervical cancer include persistent HPV infection, smoking and an immune system that may be weakened by another health condition or by infection with HIV (the human immunodeficiency virus). A common bacteria called chlamydia, which can infect the reproductive system through sexual contact, may also increase the risk of cervical cancer.

You can reduce your risk of developing cervical cancer by having screening tests. Receiving the vaccine that protects against HPV infection before being exposed to the virus also reduces the risk.

Q: I am in a same-sex relationship. Do I need cervical cancer screening?

A: Because HPV is so common, women in the LGBTQ+ communities are at the same risk as heterosexual women, and screening for cervical cancer is recommended.

Q: I am going to be treated with radiation and want to preserve my fertility. What are my options?

A: Before treatment begins, discuss options with your healthcare provider that might be right for you. Ask about newer options for preserving fertility, such as oocyte cryopreservation, also known as egg freezing. In this process, the unfertilized eggs are removed, frozen and stored for later use.

Q: I had a hysterectomy as treatment for my cervical cancer and am now experiencing hot flashes. Do you have any tips for me?

A: There are several medications that potentially help decrease hot flashes. Talk to your healthcare provider to determine the best options for you.

The following tips may also help:

Identify the triggers for your hot flashes. For many, hot flashes can be triggered by stress, a hot shower, caffeine or spicy foods.
Change your lifestyle habits to cope with your specific triggers. That may mean regular exercise, using relaxation techniques and changing your diet.
Dress in layers so that you can remove clothing if needed.
Keep ice water handy to help you cool off.
Avoid synthetic materials, especially at nighttime. Wear pajamas and use sheets made of cotton.
Take a cool shower before going to bed.

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Staging

Cancer staging is a way of describing the size and location(s) of the cancer, if it has spread and whether it is having an effect on other parts of the body, particularly those close to the cervix such as the bladder or rectum. Staging is based on the results of a physical exam, imaging scans and biopsies.

The main stages of cervical cancer as classified by the International Federation of Gynecology and Obstetrics (FIGO) are:

Stage I. The cancer has spread from the cervix lining into the deeper tissue but is still just found in the uterus.
Stage II. The cancer has spread beyond the uterus to nearby areas, such as the vagina or tissue near the cervix, but it is still inside the pelvic area.
Stage III. The tumor involves the lower third of the vagina and/or
Has spread to the pelvic wall
Causes hydronephrosis (swelling of the kidney)
Stops a kidney from functioning
Involves regional lymph nodes (small, bean-shaped organs that help fight infection)
Stage IVA. The cancer has spread to the bladder or rectum, but has not spread to other parts of the body.
Stage IVB. The cancer has spread to other parts of the body.

Stages are divided into smaller sub-stages that provide additional detail about the cervical cancer and potentially direct the treatment options.

The Importance of Clinical Trials

Clinical trials are the standard by which we measure the worth of new treatments and the quality of life of patients as they receive those treatments. For this reason, doctors and researchers urge people with cancer to take part in clinical trials. Your doctor can guide you in making a decision about whether a clinical trial is right for you. Here are a few things that you should know:

Often, people who take part in clinical trials gain access to and benefit from new treatments.
Before you participate in a clinical trial, you will be fully informed as to the risks and benefits of the trial.
Most clinical trials are designed to test a new treatment against a standard treatment to find out whether the new treatment has any added benefit.
You can stop taking part in a clinical trial at any time for any reason.

Your Support Team

When you are diagnosed with cervical cancer, you’re faced with a series of choices that will have a major effect on your life. Your health care team, family members and friends will likely be an invaluable source of support at this time. You also can turn to these resources:

Oncology social workers provide emotional support for people with cancer and their loved ones. These professionals can help you cope with the challenges of a cancer diagnosis and guide you to resources. CancerCare offers free counseling from professional oncology social workers who understand the challenges faced by people with cancer and their caregivers. CancerCare’s professional oncology social workers work with you one-on-one to develop strategies for coping with treatment and its side effects.

Oncology social workers also can help you communicate with your doctor and other members of your medical care team about the health care issues that are important to you.

Support groups provide a caring environment in which you can share your concerns with others in similar circumstances. Support group members come together to help one another, providing insights and suggestions on ways to cope. At CancerCare, people with cancer and their families can participate in support groups in person, online or on the telephone.

Financial help is offered by a number of organizations to assist with cancer-related expenses such as transportation to treatment, child care or home care.

To learn more about how CancerCare helps, call us at 800-813-HOPE (4673) or visit www.cancercare.org.