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Cervical Cancer: NCCN Guidelines for Patients

July 15, 2022 - read ≈ 7 min

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The NCCN Guidelines for Patients were developed by the National Comprehensive Cancer Network (NCCN). NCCN is an organization that unites leading cancer care centers in the United States of America. Its activities are focused on scientific research, treatment and education of patients.

Cervical cancer basics

Cervical cancer is a common cancer of the female reproductive system. Most cervical cancers are caused by long-term infection with human papillomavirus (HPV).

HPV is the most common sexually transmitted infection (STI). The use of Pap smears has resulted in much lower rates of cervical cancer in the United States.

The cervix

The cervix (also called the uterine cervix) is the narrow, lower end of the uterus. The uterus is where a baby grows and develops before being born.

During birth, the cervix opens (dilates) and thins (effaces) to allow the baby to move into the vagina. The vagina, or birth canal, is the muscular passage through which babies are born.

An ovary and a fallopian tube are on each side of the upper uterus. The fallopian tubes connect to the top part of the uterus. The ovaries make eggs for sexual reproduction. They also make hormones that affect breast growth, body shape, and the menstrual cycle.

Eggs pass out of the ovary and travel through the attached fallopian tube into the uterus. The cervix, uterus, vagina, ovaries, and fallopian tubes are part of the female reproductive system.

To understand cervical cancer, it helps to understand the structure of the cervix. The ectocervix and endocervix are the thin layer of tissue that lines the outer part and inner parts of the cervix. The cervical stroma is the thick layer of muscular tissue beneath the cervical lining. The parametrium is the fat and connective tissue that surrounds the uterus (and cervix) and connects it to the pelvis.

Most cervical cancers start in the lining of the cervix. The ectocervix is the outer part of the cervix. It appears rounded and extends into the vagina.

The ectocervix can be seen during an examination of the vagina and cervix using a tool called a speculum. It is lined with cells called squamous cells. In the center of the ectocervix is a narrow opening called the external os. During menstruation, the external os opens slightly to allow blood to pass into the vagina.

The endocervix (endocervical canal) is the inner part of the cervix that forms a canal between the vagina and the body of the uterus. The endocervix is lined with columnar (glandular) cells that make mucus. The inner os is the upper part of the endocervix that serves as an opening between the uterus and the cervix.

The area where the endocervix and ectocervix meet is called the squamo-columnar junction or the transformation zone. Most cervical cancers and pre-cancers start in the ectocervix portion of the transformation zone.

Although the cervix is part of the uterus, uterine cancer is diagnosed and treated differently than cervical cancer. This patient guide does not discuss treatment of uterine cancers, such as endometrial cancer and uterine sarcomas.

The start of cervical cancer

Cervical cancer starts as areas of abnormal, microscopic cells on the surface of the cervix. These changes are known as cervical dysplasia or cervical intraepithelial neoplasia (CIN).

Mutations (changes) in the DNA of these cells cause them to become abnormal and potentially cancerous. If left untreated, cervical dysplasia may become cervical cancer.

CIN is graded based on how abnormal the cells look when viewed under a microscope. The possible grades are 1, 2, or 3. The lower the grade, the less abnormal the cells. Cervical dysplasia becomes cancer when the abnormal cells invade the muscular tissue beneath the cervical lining (the cervical stroma).

An area of dysplasia or cancer is also referred to as a lesion. Low-grade squamous intraepithelial lesion (LSIL) refers to mild dysplasia (CIN 1). High-grade squamous intraepithelial lesion (HSIL) refers to moderate or severe dysplasia (CIN 2 and 3). HSIL is considered a pre-cancer.

Risk factors

A risk factor is something that increases the risk of developing a disease. Some people with no known risk factors may develop cervical cancer, while others with risk factors may not.

HPV infection

Almost all cervical cancers are caused by long- term infection with HPV. HPV is an extremely common sexually transmitted infection (STI).

Most sexually active people have or had HPV at one point. Most are unaware that they are or were infected.

In most people, the immune system gets rid of (“clears”) HPV from the body. In other people, the virus causes long-term cell changes that develop into cancer. The progression to cancer often occurs decades after the initial infection. Doctors are still learning why one person gets cervical cancer and another does not. Other types of cancer caused by HPV include anal, head and neck, penile, vaginal, and vulvar cancers.

There are more than 100 types (strains) of HPV. Infection with some strains is more likely to lead to cancer. High-risk forms of HPV include HPV-16 and HPV-18. Other HPV types can cause abnormal skin growths, called warts, to form on the anus, genitals, or other areas of the body.

A vaccine that protects against 9 different strains of HPV, including the highest-risk strains, is available in the United States. While previously only recommended for routine use in adolescents and young adults, vaccination is now an option for adults aged 45 and under.

There are two other HPV vaccines available in other parts of the world. One protects against HPV-16 and HPV-18 only. The other targets these highest-risk strains as well as two additional types. The vaccine is most effective in younger people (ideally under age 13) because they are less likely to have been exposed to HPV. Also, while the vaccine can prevent new HPV infections, it does not treat existing HPV infections or HPV-related cancer.

Other risk factors

Other risk factors for cervical cancer are listed below. Some of these lead to a higher risk because they either increase the risk of being exposed to HPV or they weaken the immune system, which can make it harder for the body to clear HPV infection.

  • A history of smoking
  • Having given birth more than once (called “high parity” or multiparity)
  • Oral contraceptive (birth control) use
  • Being sexually active at an early age
  • A high number of sexual partners
  • A history of sexually transmitted infection
  • Certain autoimmune diseases
  • A weakened immune system due to human immunodeficiency virus (HIV) or AIDS, for example

Types of cervical cancer

Most cervical cancers start in the ectocervix. The ectocervix is lined with squamous cells. Cancer that forms in squamous cells is called a squamous cell carcinoma.

About 2 out of 10 cervical cancers form in the endocervical canal. The endocervix is lined with cells that make mucus. These cells are referred to as glandular, gland-like, secretory, or columnar cells. Cancers that form in glandular cells are called adenocarcinomas.

Less commonly, the cancer may contain both squamous and adenocarcinoma cells. These cancers are referred to as adenosquamous carcinomas. They are sometimes called “mixed” tumors.

Treatment for squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma is the focus of Part 4.

The rarest and most aggressive type of cervical cancer is neuroendocrine carcinoma of the cervix (NECC). Treatment for small cell NECC is the focus of Part 5. This patient guide does not discuss other types of cervical cancer such as glassy- cell carcinomas, sarcomas, or other tumor (histologic) types.

Key points

  • The cervix is the lower, narrow part of the uterus that connects the uterus to the vagina.
  • The rounded, outer part of the cervix that extends into the vagina is called the ectocervix.
  • The narrow opening in the center of the ectocervix is the external os. It allows fluids to pass between the vagina and uterus.
  • The endocervix is the canal between the vagina and the body of the uterus.
  • The area where the endocervix and ectocervix meet is called the squamo-columnar junction or the transformation zone.
  • Most cervical cancers and pre-cancers start in the ectocervix portion of the transformation zone.
  • Squamous cell carcinoma is the most common type of cervical cancer, followed by adenocarcinoma. Adenosquamous carcinomas are less common.
  • Neuroendocrine carcinoma of the cervix (NECC) is a rare and aggressive type of cervical cancer.
  • The risk factor most strongly linked with cervical cancer is long-term infection with HPV. HPV is a very common sexually transmitted infection.


You can read more about Cervical Cancer, its treatment methods and follow-up after treatment in the full text of the recommendations for patients by downloading it below.

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