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Cervical Cancer

Pathology || Signs and Symptoms || Diagnosis || Treatment || Overview ||
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Pathology





Cervical cancer can develop from one of the two types of cells in the cervix: squamous epithelial cells or columnar epithelial cells.

Most cases of cervical cancer originate from squamous cells. Almost all cases of cervical cancer are associated with human papilloma virus (HPV) infection. Specific strains, namely 16, 18, and 31, are present in the bulk majority of all cervical cancer cases.

So how does the human papilloma virus cause cancer? It starts when the virus infects the base layer of the epithelial lining of the cervix. From there the virus creates two proteins that wreak havoc on cell growth and division. It has been shown that these viral proteins cause rapid destruction of normal cellular proteins involved in suppressing tumor growth (ie: p53); they also prevent cell death, and keep cells from entering "old age" by increasing the activity of an enzyme known as telomerase. All of these things allow infected cervical cells to grow and divide like mad; the end result is cervical cancer.

Although HPV is associated with most cases of cervical cancer, it is not the sole factor! Other events must fall into place for HPV to work its dark magic on the cervical epithelium. These other events vary from person to person and are not particularly well known, but may include other genetic predispositions and immune system dysfunction that allows HPV infected cells to go from pre-cancerous to cancerous.

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Signs and Symptoms

Cancer of the cervix can cause abnormal bleeding and discharge from the vagina. Pelvic pain, especially during intercourse (dyspareunia) can also occur. In addition, like all cancers, it can cause a slew of non-specific symptoms like weight loss and fatigue. Unfortunately, many patients with early stage cervical cancer do not necessarily have symptoms; when symptoms do develop, the cancer is usually in a much more advanced stage.

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Diagnosis

Diagnosis of cervical cancer usually starts with a pap smear. There are several different results that come back from a pap smear. They are "normal", "atypical squamous cells of undetermined significance" (ASC-US), "atypical squamous cells - cannot rule out high grade lesion" (ASC-H), "low grade squamous intraepithelial lesion" (LSIL), and "high grade squamous intraepithelial lesion" (HSIL).

If a pap smear comes back as abnormal then "reflex" HPV testing is done to determine if the specimen is infected with one of the common cancer causing HPV strains.

Regardless of HPV status, most patients with ASC-H, LSIL, and HSIL will undergo colposcopy (ie: direct visualization of the cervix for abnormalities). If ASC-US reflex HPV testing comes back negative (ie: no cancer causing strains) then routine pap smear screening is resumed.

Pap Smear Diagnosis

Colposcopy allows direct visualization of the cervix for potential biopsy of abnormal areas. The results of the biospy give a tissue diagnosis. They are recorded in grades depending on how "bad" the tissue looks. The possible results are cervical intraepithelial neoplasia (CIN) grades 1 through 3, or frank cancer. CIN grades refer to how dysplastic (ie: pre-cancerous) the tissue looks. It is important to note that CIN refers to "pre-cancerous" lesions. The degree of dysplasia has important ramifications for treatment.

Possible Pap Smear Results (1st test) Possible Colposcopy Biopsy Results Please note that pap smear results do not necessarily correlate directly with biospy results. In other words a pap smear result of LSIL would not necessarily correlate with a biopsy result of CIN-3.
(1) Normal (1) Normal
(2) ASC-US (2) CIN - 1
(3) ASC-H (3) CIN - 2
(4) LSIL (4) CIN - 3
(5) HSIL (5) Cancer

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Treatment

Treatment depends on the results of the biopsy done during colposcopy. If the result is CIN-1 patients are followed with pap smears every 4 to 6 months with repeat colposcopy if needed. After three negative pap smears, patients generally resume normal pap screening (once yearly in most cases).

If the result is CIN-2 or CIN-3 then patients usually undergo ablation therapy. Ablation therapy refers to removing a rind of cervical tissue in order to remove any dysplastic (ie: pre-cancerous) areas. The most common ways of doing this are LEEP (loop electrosurgical excision procedure), cold knife conization, laser ablation, or cryotherapy.

If the biopsy result comes back as cancer the first step is to determine the extent of spread. The grade of the cancer determines the TNM stage. Different TNM stages have different treatments. A stage 1 cancer would be removed surgically. Whereas stage 4 (most advanced) cancers are often treated with radiation and/or chemotherapy.

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Overview

Cervical cancer most commonly arises from squamous epithelium. It is highly associated with HPV infection, specifically strains 16, 18, and 31. Many women are asymptomatic until late in the disease; however, abnormal bleeding or discharge, weight loss, and fatigue can occur. Diagnosis begins with the Pap smear followed by colposcopy and biospy of abnormal areas. Treatment depends on the stage of cancer.

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Related Articles

- Breast cancer

- Endometrial cancer

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References and Resources

(1) Schiffman M, Wentzensen N. From human papillomavirus to cervical cancer. Obstet Gynecol. 2010 Jul;116(1):177-85.

(2) Van Doorslaer K, Burk RD. Evolution of human papillomavirus carcinogenicity. Adv Virus Res. 2010;77:41-62.

(3) Grce M, Matovina M, Milutin-Gasperov N, Sabol I. Advances in cervical cancer control and future perspectives. Coll Antropol. 2010 Jun;34(2):731-6.

(4) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

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