Cervical cancer is known to be a slow-growing tumor. Before cancer develops in the cervix, the cells of the cervix go through certain kind of transformation known as dysplasia, in which abnormal growth of cells occur in the cervical tissue. With the passage of time, the abnormal cells grow into malignant cells and start invading surrounding structures.
After diagnosis of cervical cancer has been made, tests are done to determine the extent of spread of cancer within the cervix or to other parts of the body. This is called staging of the tumor. Like any other malignant cancer, cervical cancer has great potential to spread from where it began to other parts of the body. It is significant to determine the stage in order to devise the treatment plan for the patient.
Certain tests can be done to stage the cervical cancer. Cystoscopy or proctoscopy can be done to check if cancer has spread to the urethra or bladder. Computed tomography scan (CT), Magnetic resonance imaging (MRI) and Positron emission tomography scan (PET) are major tests done to stage the extent of the disease.
The following stages are used for cervical cancer:
- Carcinoma in Situ (Stage 0)
- Stage I
- Stage II
- Stage III
- Stage IV
Carcinoma in situ (Stage 0)
It is a pre-invasive stage of cervical cancer.
Premalignant conditions of cervical cancer and their grading:
Cervical intraepithelial neoplasia (CIN) is a premalignant condition in which atypical cells appear on the surface of the cervix. “Intraepithelial” denotes that the atypical cells are developing in the epithelial tissue of the cervix. The word “neoplasia” means abnormal growth of new cells. CIN is also referred as cervical dysplasia. CIN may be diagnosed through the Papanicolaou technique or colposcopic examination. But histopathological examination of a cervical biopsy is always considered as a gold standard in order to label the specimen as premalignant or malignant.
The cervical intraepithelial neoplasia (CIN) is commonly used term in laboratory reports referring to dysplastic changes in the cervix. CIN is further classified based on extent of dysplastic changes in the cervical epithelial tissue:
CIN 1 refers to the dysplastic changes restricted to the basal 1/3 of the cervical epithelium (mild dysplasia). In CIN 1, there is good maturation with negligible nuclear aberrations. Only few mitotic figures are seen. Atypical cells are limited to the deeper layers (lower third) of the epithelium. Research has shown that it is possible to observe cytopathic changes due to HPV in the full thickness of the epithelium even in mild stages of cervical dysplasia.
CIN 2 is considered as a more serious lesion. In CIN 2, dysplastic cellular changes are limited to the basal 2/3 of the epithelial lining. CIN 2 was previously referred as moderate dysplasia. Major features of CIN 2 are presence of atypical cellular changes in the lower half of the epithelium and more marked nuclear irregularities than in CIN 1, presence of mitotic figures throughout the lower half of the epithelium.
CIN 3 is also referred as a high-grade lesion but it is even more serious than CIN 2. It is truly a precancerous stage in which the dysplastic changes in the epithelium are seen in greater than 2/3 of the cervical epithelial lining up to and including full-thickness lesions. For this reason, it is called severe dysplasia or carcinoma in situ. In CIN 3, differentiation and stratification are not seen throughout the epithelium. Nuclear abnormalities are seen throughout the thickness of the epithelium. Numerous mitotic figures are seen. It is also called as Stage 0 of cervical cancer. Pap smear can detect these changes prior to development of invasive cervical cancer.
Other Premalignant conditions diagnosed on pap smear:
ASC (atypical squamous cells)
Squamous cells are the thin and flat epithelial cells of the surface of the cervix. Atypical cells can be further classified into two groups:
ASC-US (atypical squamous cells of undetermined significance)
The squamous cells are mildly abnormal or atypical. These changes are related to HPV infection.
ASC-H (atypical squamous cells of high-grade squamous intraepithelial lesion)
ASC-H has high risk of developing into cervical cancer. This condition refers to the presence of numerous atypical squamous cells on the surface of the cervix.
AGC (atypical glandular cells)
Glandular cells are known to produce mucus and are present in endocervical canal (opening in the center of the cervix). When these glandular appear abnormal, condition is referred as AGC.
AIS (endocervical adenocarcinoma in situ)
Precancerous cells can also be found in the glandular tissue. They can develop into adenocarcinoma of cervix.
LSIL (low-grade squamous intraepithelial lesion)
Low-grade refers to early variations in the size and shape of the epithelial cells. LSILs are referred as mild abnormalities most probably caused by HPV infection. CIN 1 is considered as LSIL.
HSIL (high-grade squamous intraepithelial lesion)
High-grade squamous intraepithelial lesions consist of more noticeable variations in the size and shape of the epithelial cell linings. These atypical cells have potential to develop into precancerous cells. HSILs consist of extremely severe dysplastic changes and have a higher probability of progressing to invasive cervical cancer. CIN 2 and CIN 3 are commonly referred as HSILs.
In stage 1, cancer has spread from the cervical epithelial lining into the deeper tissue but it is yet not found in the uterus. Cancer has not spread to other parts of the body. About 45% of women with cervical cancer are diagnosed at stage 1. This stage is further divided into smaller classes for better understanding.
The cancer can only be seen under a microscope. Imaging tests of tissue samples can also be used to determine size of the cancer.
There is a cancerous area of less than 3 millimeters (mm) in depth
There is a cancerous area 3 mm to less than 5 mm in depth.
In this stage, the tumor is yet to invade any surrounding tissues i.e. uterus.
The tumor 5 mm or more in depth and less than 2 centimeters (cm) wide.
The tumor is 2 cm or more in depth and less than 4 cm wide.
The tumor is 4 cm or more in width.
In stage 2, malignant cells have spread beyond the uterus to the nearby structures like vagina but they have not invaded pelvic wall yet. Cancer has not spread to other parts of the body.
This stage is also divided into smaller groups to describe malignancy better.
The tumor is confined to the upper 2/3rd of the vagina. It has not invaded parametrial area.
The tumor is less than 4 cm wide.
The tumor is 4 cm or more in width.
The tumor has spread to the parametrial area. The tumor has not spread to pelvic wall yet.
In stage III, cancer spread to lower 1/3rd of the vagina and the pelvic wall. Kidney problems are characteristic of this stage. Swelling of the kidney, called hydronephrosis is most common kidney issue at this stage. Decreased functioning of the kidney and involvement of regional lymph nodes can also occur. There is no distant spread of cancer cells.
The tumor involves the lower third of the vagina, but it has not grown into the pelvic wall.
The tumor invades the pelvic wall and affects a kidney.
The tumor involves regional lymph nodes.
The cancer has spread to lymph nodes in the pelvis.
The cancer has spread to para-aortic lymph nodes. These lymph nodes may also be found in the abdomen near the base of the spine and near the aorta.
In stage IV, malignancy has spread beyond the pelvic wall Imaging tests can reveal the involvement of the bladder and rectum and other different parts of the body.
The cancer has spread to the bladder or rectum, but it has not spread to other parts of the body.
The cancer has spread to other parts of the body i.e. lungs and liver.
Cervical cancer diagnosed as stage IV disease can be diagnosed by pelvic examination or certain symptoms of cervical cancer. After staging the tumor, we can evaluate the extent of spread of the cancer. At this stage, cancer has spread to different parts of the body including bones, lungs or liver (stage IVB). Cervical cancer diagnosed in this stage is an ominous sign as prognosis of the disease is extremely poor.
Primary Tumor (T)
- Tx: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- Tis: Carcinoma in situ
- T1: Cervical carcinoma confined to the uterus- T1a: Invasive carcinoma diagnosed only by microscopy
– T1b: Clinically visible lesion confined to the cervix
- T2: Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower third of vagina- T2A: Tumor without parametrial invasion
– T2B: Tumor with parametrial invasion
- T3: Tumor extends to pelvic wall and/or involves lower third of vagina, and/or causes hydronephrosis- T3a: Tumor involves lower third of vagina, no extension to pelvic wall
– T3b: Tumor extends to pelvic wall and/or causes hydronephrosis
- T4: Tumor invades bladder or rectum, and/or extends beyond true pelvis
Regional Lymph nodes (N)
- Nx: Regional lymph nodes cannot be assessed
- No: No regional lymph nodes metastasis found
- N1: Regional lymph node metastases found
Distant Metastasis (M)
- M0: No distant metastasis found
- M1: Distant metastasis is found. It normally includes peritoneal spread and involvement of supraclavicular, mediastinal or para-aortic lymph nodes. Lung, liver and bone can also be involved.
Metastatic spread of cervical cancer
When malignant cells spread to other parts of the body, it is known as metastasis. Cancer cells break away from their primary location and spread through hematogenous or lymphatic route. The metastatic tumor consists of same type of cells as the primary tumor. For example, if cervical cancer invades the lung tissue, cervical cancer cells will be found on biopsy of the lung. That is why the disease is called metastatic cervical cancer, not lung cancer.
Cervical cancer spreads in the body by 3 ways:
Tissue. The cancer spreads locally to the nearby structures. This is called invasion.
Lymph system. Cancer cells travel through lymphatic system. Lymph vessels spread them to different parts of the body.
Blood. The cancer spreads from primary location to other parts of the body by getting into the blood.
Importance of staging of cervical cancer:
Staging of cancer is done for several reasons:
Staging of the malignancy can help the doctor in devising the treatment plan for the patient. An early-stage cancer may require surgery while an advanced-stage cancer almost always call for chemotherapy and radiotherapy with or without surgery.
Recovery of the patient depends on how early the cancer has been diagnosed. Stage of the disease has a major role in determining prognosis of the disease. Earlier stage cancer has far better prognosis and survival rates than advanced stage cancer. When cervical cancer is diagnosed at an early stage, the 5-year survival rate for women with invasive cervical cancer is 92%. If cervical cancer has invaded surrounding tissues or regional lymph nodes, the 5-year survival rate is 56%. If the cancer has metastasized to a different other part of the body e.g. liver and bone, the 5-year survival rate is 17%.
After diagnosis of cervical cancer, tests are done to find out the extent of spread of cancer within the cervix or to other parts of the body. This is called staging of the tumor. Certain pre-malignant conditions like Cervical intraepithelial neoplasia (CIN) can occur before development of invasive cervical cancer. The following stages are used for cervical cancer:
- Carcinoma in Situ (Stage 0)
- Stage I
- Stage II
- Stage III
- Stage IV
Staging of the disease is helpful in devising the treatment plan and determining the prognosis and survival rate of the patients of cervical cancer.