Stages and Grades of HIV Associated Cancer

Executive Summary

The stage of cancer (including HIV associated cancer) indicates the tumor size and the spread of the cancer cells from the site of origin. The grade indicates the microscopic appearance of the cancer cells. A TNM staging system is not used to identify the different stages of HIV associated cancer. AIDS-associated cancer, such as non-Hodgkin’s lymphoma, consists of stages (stage I-IV). The grading of Non-Hodgkin’s lymphoma (NHL) includes indolent (slow-growing, low-grade) or aggressive (fast-growing, high-grade). Stages of AIDS-related Kaposi’s sarcoma include four stages (I-IV) and depend upon ACTG staging. The grading of Kaposi Sarcoma includes a low-grade vascular tumor. The stages of AIDS-related cervical cancer include four stages (IA1, IA2, IB1, IB2, IIA, IIB, IIIA, IIIB, IVA, and IVB). Grading of cervical cancer includes grade 1, 2 and 3.

Stages and Grades of HIV Associated Cancer

The stage of cancer (including HIV associated cancer) indicates the tumour size and the spread of the cancer cells from the site of origin. The grade indicates the microscopic appearance of the cancer cells.

Two main types of staging systems are used for different types of cancer.

Number staging system

The number stages are:

Stage 0 – the cancer is confined at the site of origin and hasn’t spread.

Stage 1 – the malignant tumour is small and hasn’t spread.

Stage 2 – the malignant tumour has grown but hasn’t spread.

Stage 3 – the malignant tumour is larger and has the chance of spreading to the nearby tissues and/or the lymph nodes.

Stage 4 – cancer has spread from the site of origin to at least one other organ, often referred to as “metastatic” or “secondary” cancer.

TNM staging system

The TNM system uses a combination of letters and numbers to describe the cancer state. The TNM staging system is used depending on the cancer type.

In the TNM system:

• T denotes the tumour size, with numbers ranging from1 to 4 (1 for small, 4 for large).
• N denotes if cancer has affected any lymph nodes, with numbers ranging from 0 to 3 (0 indicates no lymph nodes have cancer, 3 indicates many do).
• M denotes if cancer has metastasized or whether cancer HIV Associated Cancer has spread to different body parts, with numbers ranging from 0 or 1 (0 denotes that it has not spread, 1 denotes that it has).

Stages of AIDS associated Lymphoma

AIDS associated cancer, such as non-Hodgkin’s lymphoma, has the following four stages.

• Stage I: Stage I of AIDS-related lymphoma is often observed in one or more lymph nodes in a group of lymph nodes or rarely in the Waldeier ring, spleen, or thymus. In stage IE, the cancer is found in areas outside the lymphatic system.

• Stage II: In stage II of AIDS-related lymphoma, the cancer is found in two or more groups of more lymph nodes above or below the diaphragm. In stage IIE of AIDS-related lymphoma, cancer has spread from a group of lymph nodes to adjacent areas outside the lymphatic system. Cancer can spread to other lymph nodes on the same side of the diaphragm. In stage II, the term bulky disease indicates a large tumour mass. The size of the tumour for bulky disease depends on the type of lymphoma.

• Stage III: Stage III cancer is found in groups of lymph nodes above and below the diaphragm or the spleen and the lymph nodes above the diaphragm.

• Stage IV: In stage IV AIDS-related lymphoma, cancer:

• has spread throughout to one or more organs beyond the lymphatic system; or

• is localized in two or more lymph nodes that are either above or below the diaphragm and in one organ outside the lymphatic system and not in the vicinity of the affected lymph nodes: or

• is found in the number of lymph nodes both above and below the diaphragm and any body part outside the lymphatic system; or

• is found in the bone marrow, liver, cerebrospinal fluid (CSF) or multiple places in the lung. Cancer has not spread into the bone marrow, liver, CSF, or lung from surrounding lymph nodes^​1​.

Grading of non-Hodgkin’s Lymphoma (NHL)

To assess the grade of NHL, the pathologist conducts a microscopic examination of lymph nodes or other tissue samples. The grade is an explanation of how the cancer cells look and behave compared to the normal cells. Different types and subtypes of NHL are generally described as indolent (slow-growing, low-grade) or aggressive (fast-growing, high-grade). Some NHL subtypes cannot be easily classified because they have both indolent and aggressive NHL characteristics.

Indolent or Low-grade NHL

Indolent or low-grade denotes that the cancer cells are well differentiated. The characteristics of these cells are more or less like normal cells. Low-grade NHL types progress slowly and usually cause only a few symptoms when they develop. As a result, low-grade NHL often spreads to other parts of the body during diagnosis. They usually spread to the spleen and bone marrow. Some types of low-grade NHL may recur or become high-grade NHL that require more aggressive treatment.

Aggressive or High-grade NHL

Aggressive or high grade denotes that the cancer cells are undifferentiated or poorly differentiated. These type of cancerous cells looks and acts abnormally. High-grade NHL types tend to grow and spread quickly. They tend to spread rapidly to lymph nodes and other body organs. High-grade NHL types usually cause symptoms and require treatment immediately.

Stages of AIDS-Related Kaposi Sarcoma

No universally accepted system for the staging of AIDS-related Kaposi’s sarcoma staging is available. The most commonly used AIDS-related Kaposi sarcoma staging method in adults was developed by the AIDS Clinical Trial Group (ACTG) of the National Institutes of Health (NIH)^​2​. It is to be noted that this staging system is most commonly used in research studies. AIDS-related Kaposi’s sarcoma has four stages:

• Stage I: In Stage I Kaposi sarcoma, small nodules and macules are located mainly in the lower extremities.
• Stage II: In stage II of the Kaposi sarcoma plaques mainly affects lower extremities, sometimes associated with a few nodules.
• Stage III: Multiple angiomatous nodules and plaques, including those of the lower extremities, which are often ulcerated.
• Stage IV: Multiple angiomatous plaques and nodules extending beyond the lower extremity are found^​3​.

In ACTG staging, patients with Kaposi Sarcoma are categorised based on three parameters.

• Extent of tumour (T): A good prognosis (T0) is associated with disease localized to the skin or with minimal involvement of oral cavity. The prognosis is considered to be poor (T1) if there is associated lymphoedema, and involvement of oral cavity involvement or additional visceral disease.
• Immune status (I): The degree of immunosuppression due to HIV infection is a critical prognostic factor. Patients having CD4 count more than 200 cells/μl are considered to have a good prognosis (I0), while those with a low CD4 count are considered to have a poor prognosis (I1).
• Severity of systemic illness (S): Patients with poor risk include the following characteristics (S1): history of opportunistic infection, B symptoms (diarrhoea for two weeks or more, weight loss, night sweats and unexplained fever), and thrush. Patients without these factors have a better prognosis (S0)^​4​.

Grading of Kaposi Sarcoma

Tumors in Kaposi’s sarcoma (KS) are often considered as low-grade vascular tumour which is linked with Kaposi’s sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection^​5​.

Stages of AIDS-related Cervical Cancer

Cervical cancer is globally the second most common cancer among women. Cervical cancer is a leading cause of early mortality among patients because it affects relatively young women. Staging, as classified by the International Federation of Gynecology and Obstetrics (FIGO), is widely used for staging cervical cancer.

• Stage IA1: Invasive carcinoma. Stromal invasion ≤7 mm in horizontal spread and ≤3 mm in depth.
• Stage IA2: Invasive carcinoma diagnosed by microscopy and is confined to the cervix. Stromal invasion ≤7 mm in horizontal spread and >3 mm to ≤5 mm in depth.
• Stage IB1: Invasive carcinoma diagnosed by microscopy and is confined to the cervix. Microscopic lesion >IA2 or clinically visible lesion ≤4 cm.
• Stage IB2: Invasive carcinoma confined to the cervix. Clinically visible lesion >4 cm.
• Stage IIA: Tumour spread beyond the cervix up to the vagina but not to the lower third of the vagina and devoid of any parametrial invasion.
• Stage IIB: Tumour spread beyond the cervix. Parametrial invasion is observed but not to the lower third of the vagina and pelvic sidewall.
• Stage IIIA: Tumour spread to the lower third of the vagina but not to the pelvic sidewall.
• Stage IIIB: Tumour spread to the pelvic sidewall. Comorbidities such as non-functioning kidney or hydronephrosis may be observed.
• Stage IVA: Tumour spread into rectum or bladder.
• Stage IVB: Distant metastasis.

Grading of Cervical Cancer

A pathologist or histopathologist performs a microscopic analysis of the cervical cancerous cells and grades them on a scale of 1 to 3:

• Grade 1: The cancerous cells appear similar to healthy cells. The growth of the cells is comparatively slower than high-grade tumour cells.
• Grade 2: The cancerous cells appear similar to healthy cells, and the growth is faster than the grade 1 cells.

Grade 3: The cancerous cells appear similar to healthy cells. They grow and spread faster than grade1 and grade 2 cells. Grade 3 cancers often need more intensive treatment regimens than lower-grade cancer cells^​6​.

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