Adenocarcinoma of Cervix
Microscopic pathology image of cervix showing Adenocarcinoma.
What are the other Names for this Condition? (Also known as/Synonyms)
- Adenocarcinoma of Uterine Cervix
- Cervical Adenocarcinoma
What is Adenocarcinoma of Cervix? (Definition/Background Information)
- Carcinoma of the Cervix, the second most common cancer in women worldwide, is a malignant (capable of invading nearby and distant tissues) tumor of the cervix, which is the lower part of the uterus/womb
- The cervix is the tube that connects the uterus to the vagina. The inner part of this tube is lined by tall cells that secrete mucus (glandular cells) and the outer portion that opens into the vagina is covered by flattened cells (squamous cells). The junction between these two cells types, called the transformation zone, is the usual site of origin of Cervical Cancer
- The development of Cervical Cancer occurs slowly and the process of pre-cancerous changes (dysplasia) leading onto invasive cancer, generally takes place over years. Hence, periodic screening of women with Pap smears helps in early detection and management of any pre-cancerous change, before full blown malignancy develops
- Adenocarcinomas arise from the glandular cells of the inner portion of the cervix (the endocervix) and account for 10-20% of all Cervical Cancers. After squamous cell cancers, Adenocarcinomas of Cervix are the second most common type of tumors, affecting the cervix. This differentiation is based on the appearance of cells, when observed under a microscope
- Screening with Pap smear helps in early detection of pre-cancers and cancers. However, when compared to squamous cell carcinomas of the cervix, Pap screening for adenocarcinomas has not been proven to be as successful in reducing the number of invasive cancers. This is because the tumor is located higher up in the cervix and hence, the abnormal cells may not be sampled during a Pap test
- 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 Cervical Adenocarcinoma; then, the tumor is staged (growth and spread of cancer is examined) and treatment options chosen, based on the staging
Who gets Adenocarcinoma of Cervix? (Age and Sex Distribution)
- Cervical Adenocarcinoma usually occurs in women during their mid-life (average age around 37 years). A small proportion of cancer (about 20%) is found in women over 65 years
- Hispanic women are commonly affected (in the United States), followed by African-Americans, Asians, and Caucasians
What are the Risk Factors for Adenocarcinoma of Cervix? (Predisposing Factors)
The following factors increase the risk of Adenocarcinoma of Cervix:
- Infection with human papilloma virus (HPV):
- 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
- History of diethylstilbestrol (DES, a synthetic form of estrogen) use in mothers: Female children of women, who took this drug while pregnant, developed adenocarcinoma of the cervix and vagina, more commonly than the rest of the population
- Lack of periodic/regular Pap smear tests
- Weakened immune system as a result of disease, like AIDS, or due to immune-suppressing drugs
- History of cervical cancer in the family
- Having the first child at a young age (before 17 years) and having multiple pregnancies
Other factors that may increase risk of cervical cancer include Chlamydia infection, long-term oral contraceptive use, a diet lacking fruits and vegetables, and even poverty.
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 Adenocarcinoma of Cervix? (Etiology)
- The exact reason behind the development of Adenocarcinoma of Cervix is still not completely known
- 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 aide in cancer development are yet to be fully explained
What are the Signs and Symptoms of Adenocarcinoma of Cervix?
Signs and symptoms of Adenocarcinoma of Cervix may include:
- Abnormal vaginal bleeding
- Pain during and bleeding after intercourse
- Menstrual cycle disturbances
- Abnormal vaginal discharge
- Anemia (due to bleeding)
- Loss of weight, loss of appetite
Some women do not have any symptoms and are diagnosed as having Cervical Adenocarcinoma, after an abnormality has been detected on a Pap test.
How is Adenocarcinoma of Cervix Diagnosed?
In order to make a diagnosis, a physician will take a detailed history followed by a physical and pelvic exam. A Pap smear, if not performed already, may be ordered as a screening procedure. An abnormal Pap smear warrants further testing. Some of the definitive tests that help in diagnosing Cervical Cancer include:
- 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
- Rarely, a complete excision of the uterus and cervix becomes necessary
If a diagnosis of cancer is made on biopsy, further imaging (or other) studies may be conducted. These include:
- Chest X-ray
- CT (computed tomography) or MRI (magnetic resonance imaging) scan of the abdomen/pelvis, or other suspected areas of spread
- PET (positron emission tomography) scan to help evaluate the extent of disease spread
- 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
- Additionally, blood tests (such as complete blood count), liver and kidney function tests, may also be carried out
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 Adenocarcinoma of Cervix?
The complications of Adenocarcinoma 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
How is Adenocarcinoma 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
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 Adenocarcinoma of Cervix include:
- 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
- Medications are used to kill the tumor cells, which may be given as oral pills or injected into veins
- Drugs commonly used to treat cervical cancer include cisplatin, carboplatin, paclitaxel, gemcitabine, and topotecan
- 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
- 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
How can Adenocarcinoma of Cervix be Prevented?
Some steps for the prevention of Adenocarcinoma of Cervix include:
- Use of measures to prevent sexually-transmitted infections, such as usage of condoms, avoiding multiple sexual partners
- 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
What is the Prognosis of Adenocarcinoma of Cervix? (Outcomes/Resolutions)
- Women with early-stage Adenocarcinoma of Cervix have better outcomes, compared to those with more advanced cancer conditions
- Almost all women diagnosed and treated at Stage 0 survive for 5 years post-diagnosis (5-year survival rate of 99-100%). This number steadily drops with cancer stage progression; less than 20% of individuals with stage IV disease survive for 5 years, following diagnosis and treatment
Additional and Relevant Useful Information for Adenocarcinoma of Cervix:
- Cervical Carcinoma is the 8th most common cancer in females, in the United States
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 CDC (Centers for Disease Control and Prevention) may be contacted for more information.
What are some Useful Resources for Additional Information?
National Cervical Cancer Coalition (NCCC)
PO Box 13827, Research Triangle Park, NC 27709
Phone: (800) 685-5531
Fax: (919) 361-8425
American Cancer Society (ACS)
1599 Clifton Road, NE Atlanta, GA 30329-4251
Toll-Free: (800) 227-2345
TTY: (866) 228-4327
National Cancer Institute (NCI)
U.S. National Institutes of Health
Public Inquiries Office
Building 31, Room 10A03
31 Center Drive, MSC 8322 Bethesda, MD 20892-2580
Phone: (301) 435-3848
Toll-Free: (800) 422-6237
TTY: (800) 332-8615
National Breast and Cervical Cancer Early Detection Program (NBCCEDP)
References and Information Sources used for the Article:
http://www.cancer.org/cancer/cervicalcancer/ (accessed on 02/21/2014)
http://www.cap.org/apps/docs/reference/myBiopsy/cervicaladenocarcinoma.pdf (accessed on 02/26/2014)
Current Medical Diagnosis and Treatment 2014, 53rd Edition; Edited by Maxine A.Papadakis, MD and Stephen J. McPhee, MD; McGraw Hill Education
Helpful Peer-Reviewed Medical Articles:
Wang SS, Sherman ME, Hildesheim A, et al. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000. Cancer 2004; 100:1035.
Madeleine MM, Daling JR, Schwartz SM, et al. Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix. Cancer Epidemiol Biomarkers Prev 2001; 10:171.
Vizcaino AP, Moreno V, Bosch FX, et al. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer 1998; 75:536
Mathew, A., & George, P. S. (2009). Trends in incidence and mortality rates of squamous cell carcinoma and adenocarcinoma of cervix–worldwide. Asian Pac J Cancer Prev, 10(4), 645-650.
Steeper, T. A., & Wick, M. R. (1986). Minimal deviation adenocarcinoma of the uterine cervix (“adenoma malignum”). Cancer, 58(1131), 8.
Molijn, A., Jenkins, D., Chen, W., Zhang, X., Pirog, E., Enqi, W., ... & Quint, W. (2016). The complex relationship between human papillomavirus and cervical adenocarcinoma. International Journal of Cancer, 138(2), 409-416.
Ursin, G., Peters, R. K., Monroe, K., Pike, M. C., & Henderson, B. E. (1994). Oral contraceptive use and adenocarcinoma of cervix. The Lancet, 344(8934), 1390-1394.
Rahilly, M. A., Williams, A. R. W., & AL‐NAFUSSI, A. (1992). Minimal deviation endometrioid adenocarcinoma of cervix: a clinicopathological and immunohistochemical study of two cases. Histopathology, 20(4), 351-354.