Endometrioid Carcinoma of Cervix

Endometrioid Carcinoma of Cervix

Article
Sexual Health
Women's Health
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Contributed byKrish Tangella MD, MBASep 08, 2018

What are the other Names for this Condition? (Also known as/Synonyms)

  • Endometrioid Carcinoma of Uterine Cervix
  • Cervical Endometrioid Carcinoma
  • Primary Endometrioid Adenocarcinoma of Uterine Cervix

What is Endometrioid Carcinoma of Cervix? (Definition/Background Information)

  • Cervical cancer is a malignancy of the uterine cervix, which is the lower part of the uterus/womb. The cervix is the tube that connects the uterus to the vagina. Significant subsets of cancers arising from the cervix are adenocarcinomas
  • Endometrioid Carcinoma of Cervix is a rare histological variant of cervical adenocarcinoma. The classification of histological subtypes is based on the appearance of cells when observed under a microscope by a pathologist
  • This sub-classification of the tumor is important, as it may dictate the type of treatment to be provided and the prognosis of the cancer. Almost all variants of cervical adenocarcinomas are related to human papilloma virus (HPV) infection
  • Screening with Pap smear helps in early detection of pre-cancers and cancers. Any abnormality found on a Pap smear is further scrutinized with an instrument, called a colposcope, and a biopsy of the abnormal areas performed to make a diagnosis
  • If the biopsy shows Endometrioid Carcinoma of Cervix; then, the tumor is staged (growth and spread of cancer is examined) and treatment options chosen, based on the staging. The treatment may involve a combination of surgery, chemotherapy, and radiation therapy
  • The prognosis depends upon a set of several factors including the stage of the tumor, age of the individual, the size of the tumor, and many other factors. In general, early detection and adequate treatment can help achieve a better outcome. The prognosis of Cervical Endometrioid Carcinoma is generally stated to be better than other conventional cervical adenocarcinomas

Who gets Endometrioid Carcinoma of Cervix? (Age and Sex Distribution)

  • Endometrioid Carcinoma of Cervix usually occurs in women during their mid-life (average age around 37 years). A small proportion of cancer (about 20% of them) is found in women over 65 years
  • Cervical Endometrioid Carcinoma constitutes less than 5% of all cervical adenocarcinomas
  • Generally, all racial and ethnic groups are at risk and the cancer is observed worldwide

What are the Risk Factors for Endometrioid Carcinoma of Cervix? (Predisposing Factors)

The following factors increase the risk for Endometrioid Carcinoma of Cervix:

  • Infection with human papilloma virus (HPV) types:
    • HPV infection is the most important risk factor predisposing one to cervical cancer
    • The virus is transmitted sexually
    • Different subtypes of the virus exist: Types 16, 18, 31, 33, and 45, are the high-risk types associated with cancer; of which HPV-18 is the most common type with respect to adenocarcinoma
  • Sexual promiscuity (multiple sexual partners) and high-risk sexual behavior
  • Poor immune system: HIV infection or AIDS, organ transplantation, immunosuppressant medications, greatly increase risk for chronic infection
  • Lack of periodic/regular Pap smear tests
  • Smoking
  • Use of oral contraceptives for long time duration; this factor is not yet conclusively proven
  • Having the first child at a young age (before 17 years) and having had multiple pregnancies
  • Presence of other sexually transmitted infections (such as chlamydia)
  • Chronic inflammation, in some cases
  • Family history of cervical cancer: This is a relatively ‘low strength’ risk factor
  • A diet lacking fruits and vegetables
  • Poverty or poor socio-economic status

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Endometrioid Carcinoma of Cervix? (Etiology)

The human papilloma virus (HPV) infection is a major cause behind the development of Endometrioid Carcinoma of Uterine Cervix.

  • Under normal circumstances, certain genes called tumor suppressor genes, keep a check on the growth and division of cervical cells
  • HPV infection has been found to disrupt some tumor suppressor genes, thus allowing cervical cells to grow and multiply uncontrollably. However, only a small proportion of women having HPV infection, go on to develop cancer
  • Other factors that aid in cancer development are yet to be fully explained

Almost all cervical cancer types are attributed to human papilloma virus infections; around 15 different HPV types have been implicated. In rare instances, cervical cancer can occur without a preceding HPV infection. In such cases, the cause of the condition is unknown.

  • HPVs are known to have carcinogenic potency, meaning they have the potential to cause cancer
  • Of HPVs, HPV-16 and HPV-18 are most common, indicating that they have a more potent threat
  • 7 in 10 cancers are due to these two virus types
  • HPV-18 is causative for most cases of adenocarcinoma, just as HPV-16 is for squamous cell carcinomas
  • However, HPV-16 is also responsible for adenocarcinoma, but not to a great extent though

Research has shown that the human papilloma virus causes the development of cervical adenocarcinomas in the following manner:

  • The first step is an individual acquiring human papilloma virus infection:
    • High-risk individuals for HPV infections are those with multiple sexual partners, or individuals having sex with high-risk or highly promiscuous men (the more the number of partners, the greater is the risk)
    • Adolescent and young adult women have higher risk
    • Most infections are self-limiting or easily treatable, thus the main risk from HPV infection is chronicity or persistence of infection
    • Chronic or recurrent infections are a very vital aspect of progression to premalignancy
  • The next step is the persistence of HPV infection and formation of premalignant lesions (such as adenocarcinoma in situ). Several years (decades) of persistent HPV infection can result in the development of precursor to cancer
  • The final step is the development of cervical cancer from the premalignant stage: The time period of development from premalignancy to malignancy is variable, but can be very slow and may take many more years to decades. Certain genes are known to be involved in the process; but, these are not well-characterized

What are the Signs and Symptoms of Endometrioid Carcinoma of Cervix?

Signs and symptoms of Endometrioid Carcinoma of Cervix may include:

  • Abnormal vaginal bleeding
  • Pain during and bleeding after intercourse
  • Menstrual cycle disturbances
  • Abnormal vaginal discharge
  • Anemia (due to bleeding)
  • Ulceration of the cervical wall
  • In some cases, the tumor infiltration causes the cervix to take a barrel-like form

Some women do not have any symptoms and are diagnosed as having cervical adenocarcinoma, NOS after an abnormality has been detected on a Pap smear test.

Advanced cancer signs and symptoms may include:

  • Persistent feeling of abdominal bloating with nausea or vomiting
  • Changes in bowel movements, such as constipation
  • Feeling full soon, after eating less
  • Loss of appetite with weight loss
  • Fatigue, feeling tired easily
  • Frequent urination (polyuria)

How is Endometrioid Carcinoma of Cervix Diagnosed?

In order to make a diagnosis of Endometrioid Carcinoma of Cervix, a detailed medical history followed by a physical and pelvic exam is undertaken. This is followed by additional tests and procedures.

  • Pelvic examination:
    • During a pelvic examination, the healthcare provider will exam the uterus, cervix, vagina, ovaries, fallopian tubes, bladder, and rectum to check for any abnormal changes in these organs
    • Also, during the exam, the tumor may appear as a polyp (exhibiting exophytic growth pattern), or it may appear as a firm, non-polyp area (exhibiting endophytic growth pattern)
    • Small tumors that may arise in the cervical canal area may be difficult to visualize. Hence, a careful exam in a high-risk individual is recommended
  • A Pap smear, if not performed already, may be ordered as a screening procedure. An abnormal Pap smear warrants further testing
  • HPV DNA testing can be used as a tool to help screen for infections and administer vaccines

Blood tests to aid in the diagnostic process may include:

  • Complete blood count (CBC) with differential of white blood cells
  • Liver function test and kidney function test
  • Blood tests called serum tumor markers that include:
    • CA-125 test
    • Human chorionic gonadotropin (hCG)
    • Alpha-fetoprotein (AFP)
    • Lactate dehydrogenase (LDH)
    • Inhibin (hormone)
    • Estrogen and testosterone levels

Some of the definitive tests that help in diagnosing the cancer include:

Colposcopy:

  • The cervix is examined with an instrument, called a colposcope. This helps the physician get a magnified view of the cervix
  • In order for this procedure to be performed, the female individual has to lie on a table, as for a pelvic exam. An instrument, called the speculum, is placed in the vagina to keep the opening apart, in order to help the physician visualize the cervix. The colposcope is then used to get a magnified view of the inside
  • To make the abnormal areas more visible, a weak acetic acid (like vinegar) solution is applied to the cervical surface. The abnormal (suspicious) areas appear whiter than the surrounding regions. A solution of Lugol’s iodine may also be used for this purpose
  • The procedure is usually not performed, when a woman has menstrual bleeds
  • It is generally not painful, but in some women it may cause discomfort or cramping

Cervical biopsy: Biopsy is the process of removing tissue for examination. A pathologist looks at the tissue sample under a microscope, to detect any evidence of cancer. Types of cervical biopsies include:

  • Colposcopic biopsy: The abnormal areas of the cervix are visualized with a colposcope. After numbing the cervix with a local anesthetic, an instrument, called a biopsy forceps, is used to get a tissue sample.  Mild cramps, pain, and some light bleeding, may occur following the procedure
  • Endocervical curettage (endocervical scraping): The curette is an instrument that can be used to scrape out tissue. Using a curette, cells are scraped out from the endocervix (the inner part of the cervix, close to the uterus/womb) and examined under a microscope. Mild pain and bleeding maybe present following the procedure.
  • Cone biopsy or conization:
    • A cone-shaped piece of tissue is removed from the cervix during conization. The exocervix (the outer part) forms the base of this cone, while the endocervix (the inner part) forms the apex
    • The cone biopsy has the added advantage that it also serves as a treatment for pre-cancers and some early cancers

Two methods can be used to obtain a cone biopsy specimen:

  • Loop electrosurgical procedure (LEEP, LLETZ): After numbing the area with a local anesthetic, a wire loop heated with electricity is used to remove a tissue specimen. This procedure, lasting about 10 minutes, may cause some cramping and mild-to-moderate bleeding, for a few weeks
  • Cold knife cone biopsy: This procedure is performed, either under general anesthesia or under spinal anesthesia. The tissue sample is removed using a surgical scalpel or through laser

If a diagnosis of cancer is made on biopsy, further imaging (or other) studies may be conducted. These include:

  • X-ray of the abdomen and pelvic region
  • Chest X-ray: Chest X-rays are used to detect if the cancer has spread to the lung
  • Barium enema X-ray
  • CT (computed tomography) or MRI (magnetic resonance imaging) scan of the abdomen/pelvis, or other suspected areas of spread
  • Transvaginal ultrasound: Transvaginal ultrasound inserts an ultrasound probe into the vagina designed to take pictures of the insides of the uterus
  • Vascular radiological studies of abdomen and pelvic region
  • Positron emission tomography (PET scan): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material is required with this test. The radioactive material may be injected into a vein, inhaled, or swallowed. It may be performed to see if the cancer has metastasized/spread to other regions
  • Cystoscopy (to look at the inside of the bladder)
  • Proctoscopy (to look at the inside of the rectum)
  • Sometimes, an intravenous pyelogram (to find any abnormality/blockage in the urinary tract) may be conducted
  • Whole body bone scan

Note:

  • Endometrioid Carcinoma of Cervix must be differentiated with similar carcinoma arising from the uterine endometrium, in order to make a definite diagnosis. This can be achieved through specialized testing in the lab
  • A Pap smear is a very good screening tool for detecting squamous cell carcinomas of uterine cervix. However, it is not as good a screening tool for detecting adenocarcinomas of cervix. In some women, Pap smears can be negative and normal, even in the presence of cervical cancer

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Endometrioid Carcinoma of Cervix?

The complications of Endometrioid Carcinoma of Cervix could include:

  • As the cancer progresses, it may invade into the vagina and surrounding tissues
  • Over time, the lymph nodes and other pelvic organs may be affected
  • The cancer can also spread to distant organs, such as the liver and lungs
  • Side effects of chemotherapy (such as toxicity) and radiation
  • Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy
  • Recurrence of the cancer following incomplete surgical removal

How is Endometrioid Carcinoma of Cervix Treated?

Once a diagnosis of cervical cancer has been made, the extent to which the tumor has spread is assessed. This is called staging.

  • The FIGO (International Federation of Gynecology and Obstetrics) and the AJCC (American Joint Committee on Cancer) TNM staging systems - are two similar, commonly used staging systems
  • A tumor that remains confined only to the superficial layers of the cervix is said to be carcinoma in situ (Stage 0 according to AJCC system)
  • Depending on how far the tumor has spread beyond the cervix, stages I through IV are defined
  • Stage I cancer is confined wholly to the cervix (the cancer has spread to involve even the deeper layers of the cervix unlike stage 0)
  • Stage IV cancer involves the nearby organs, such as the bladder, rectum, or even other distant organs

Following is the staging protocol for cervical cancer, according to the American Joint Committee on Cancer (AJCC), updated July 2016:

Stage 0 cervical cancer (carcinoma in situ):

  • In this stage, abnormal cells are found in the innermost lining of the cervix
  • These abnormal cells may become cancer and spread into nearby normal tissue

Stage I cervical cancer: The cancer is found only in the cervix. Stage I is divided into stages IA and IB, based on the amount of cancer that is found.

  • Stage IA: A very small amount of cancer that can only be seen with a microscope is found in the tissues of the cervix
    • In stage IA1, the cancer is not more than 3 mm deep and not more than 7 mm wide
    • In stage IA2, the cancer is more than 3 mm, but not more than 5 mm deep; it is not more than 7 mm wide
  • Stage IB: It is divided into stages IB1 and IB2, based on the size of the tumor
    • In stage IB1, the cancer can only be seen with a microscope and is more than 5 mm deep and more than 7 mm wide; or the cancer can be seen without a microscope and is not more than 4 cm
    • In stage IB2, the cancer can be seen without a microscope and is more than 4 cm

Stage II cervical cancer: The cancer has spread beyond the uterus, but not onto the pelvic wall (the tissues that line the part of the body between the hips), or to the lower third of the vagina. Stage II is divided into stages IIA and IIB, based on how far the cancer has spread.

  • Stage IIA: The cancer has spread beyond the cervix to the upper two-thirds of the vagina, but not to tissues around the uterus
  • Stage IIA is divided into stages IIA1 and IIA2, based on the size of the tumor
    • In stage IIA1, the tumor can be seen without a microscope and is not more than 4 cm in size
    • In stage IIA2, the tumor can be seen without a microscope and is more than 4 cm in size
  • Stage IIB: The cancer has spread beyond the cervix to the tissues around the uterus, but not onto the pelvic wall

Stage III cervical cancer: The cancer has spread to the lower third of the vagina, and/or onto the pelvic wall, and/or has caused kidney problems. Stage III is divided into stages IIIA and IIIB, based on how far the cancer has spread.

  • Stage IIIA: The cancer has spread to the lower third of the vagina, but not onto the pelvic wall
  • Stage IIIB: The cancer has spread to the pelvic wall; and/or the tumor has become large enough to block the ureters (the tubes that connect the kidneys to the urinary bladder). This blockage can cause the kidney to enlarge or stop working

Stage IV cervical cancer: In stage IV, the cancer has spread beyond the pelvis, or can be seen in the lining of the bladder and/or rectum, or has spread to other parts of the body. Stage IV is divided into stages IVA and IVB, based on where the cancer has spread.

  • Stage IVA: The cancer has spread to the nearby organs, such as the urinary bladder or rectum
  • Stage IVB: The cancer has spread to other parts of the body, such as to the lymph nodes, lung, liver, intestine, or bone

(Source: Stages of Cervical Cancer, July 2016, provided by the National Cancer Institute at the National Institutes of Health; U.S. Department of Health and Human Services)

The treatment modality is chosen, depending on the type and stage of the tumor, age of the individual, and the need to preserve the ability to bear children. Sometimes, more than one type of treatment modalities may be necessary.

Treatment options for Endometrioid Carcinoma of Cervix may include:

Surgery:

  • Stage 0 tumors, confined to the superficial layers of cervix can be treated with cryosurgery (the cells are killed using extreme cold temperatures) or by using laser therapy
  • Conization procedure, besides helping with the biopsy, can also help in treating very early-stage cervical cancers in women, who want to preserve their childbearing ability
  • Radical trachelectomy: The surgeon removes the cervix, upper part of the vagina, and nearby lymph nodes, while preserving the ability to have children
  • Hysterectomy: In this procedure, the uterus and cervix are removed. This is done by making an incision on the abdomen (termed abdominal hysterectomy), or through the vagina (termed vaginal hysterectomy), or by using a laparoscope (termed laparoscopic hysterectomy). Surgery is performed under general or epidural anesthesia, though the ability to have children is lost. Complications, such as bleeding, infection, or damage to the urinary tract, or the intestinal system may occur in rare cases
  • Radical hysterectomy: The uterus, cervix, the upper part of the vagina and tissues, next to the uterus are removed. Additionally, some pelvic lymph nodes may also be surgically taken out. The surgery is performed under anesthesia and may be carried out, via an incision made on the abdomen or by using laparoscopy. With this invasive procedure, the ability to have children is lost. Rarely, complications such as bleeding, infection, or damage to the urinary tract or the intestinal system, may occur. Removal of lymph nodes may lead to swelling of legs (lymphedema)
  • Pelvic exenteration: The uterus, tissues surrounding the uterus, cervix, pelvic lymph nodes, and the upper part of the vagina, are removed. In addition, depending on the tumor spread, the remainder of the vagina, the bladder, rectum, and a part of the colon, may also be removed. Recovery from this surgery, takes a long period

Chemotherapy:

  • Medications are used to kill the tumor cells, which may be given as oral pills or injected into veins
  • A combination of chemotherapy medications may be used
  • Chemotherapy may be used in addition to radiation and/or surgery, to treat cancers that have spread or recurred. When chemotherapy and radiation therapy are used together, it is called concurrent chemoradiation
  • Side effects of chemotherapy may include nausea, vomiting, hair loss, loss of appetite, diarrhea, fatigue, increased risk of infection, mouth sores, and easy bruising, depending on the drugs used

Radiation therapy:

  • This procedure uses high-energy beams to kill the cancer cells
  • These beams may be delivered from outside the body (external beam radiation therapy) or the radioactive material maybe placed inside the vagina or the uterus (internal radiation therapy or brachytherapy)
  • Possible side effects may include:
    • Fatigue, nausea, vomiting, and diarrhea
    • Bladder irritation, leading to inflammation (cystitis)
    • Ovaries may be affected resulting in menstrual changes, or premature menopause
    • The vulva and vagina may be affected, causing soreness, or even scar tissue formation

Once treatment is complete, it is recommended that the individual schedule regular check-ups, based on the recommendation of the specialist treating them. 

How can Endometrioid Carcinoma of Cervix be Prevented?

Some steps for the prevention of Endometrioid Carcinoma of Cervix include:

  • Use of measures to prevent sexually-transmitted infections, such as usage of condoms, avoiding multiple sexual partners, and circumcision in men
  • Avoidance of smoking
  • Regular screening to detect pre-cancers:
    • The American Cancer Society recommends screening of women from age 21 years
    • A Pap smear is recommended every 3 years, from ages 21-29 years
    • From age 30-65 years, a Pap smear and HPV testing is recommended, once every 5 years
    • More frequent screenings are advised for women having a high-risk for cervical cancer
  • Vaccination against human papilloma virus (HPV):
    • Two vaccines have been studied and approved for use in the United States - Gardasil (against HPV types 6, 11, 16, and 18) and Cervarix (against HPV types 16 and 18)
    • Cervarix has been approved for use in females aged 10-25 years, while Gardasil may be used in the 9-26 years age group
    • The American Cancer Society recommends routine vaccination of girls at 11-12 years of age
    • HPV vaccines are not successful against women who are already infected though

What is the Prognosis of Endometrioid Carcinoma of Cervix? (Outcomes/Resolutions)

  • Women with early-stage Endometrioid Carcinoma of Uterine Cervix have better outcomes compared to those with more advanced cancer conditions
  • Almost all women diagnosed and treated at Stage 0 cervical cancer survive for 5 years post-diagnosis (5-year survival rate of 99-100%). This number steadily drops with cancer stage progression. Most variants of cervical adenocarcinoma show nearly the same prognostic rates. However, the prognosis of Endometrioid Carcinoma of Cervix is better than other conventional adenocarcinomas of the cervix
  • The prognosis for Cervical Endometrioid Carcinoma depends upon a set of several factors that include:
    • The size of the tumor and the extent of its invasion: Individuals with small-sized tumors fare better than those with large-sized tumors
    • Stage of cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
    • FIGO grade of the tumor: Tumors that are graded 1 and 2 have better prognoses than grade 3 tumors
    • Cell growth rate of the cancer
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • Individuals with bulky disease have a poorer prognosis
    • Involvement of the regional lymph nodes, which can adversely affect the prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
    • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
    • Progression of the condition makes the outcome worse
  • An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Individuals, who tolerate chemotherapy sessions better, generally have better outcomes

Additional and Relevant Useful Information for Endometrioid Carcinoma of Cervix:

  • Studies have shown (in developed countries) that the incidence of cervical cancer in a given population may be reduced by as much as 20 times through effective and wide-coverage screening programs

The U.S. National Breast and Cervical Cancer Early Detection Program (NBCCEDP) aims to provide screening tests for breast and cervical cancer to women in underserved areas, or those without health insurance, either for free or at a low cost. If needed, further testing or treatment expenses may also be covered. The US-based Centers for Disease Control and Prevention (CDC) may be contacted for more information.

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Krish Tangella MD, MBA

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