Cervical cancer is commonly known in today’s society as the type of cancer that is caused by a virus. Cervical Cancer is very common in women worldwide and is the third most common malignancy in women. It is a disease that affects women in both the developing world as well as in developed countries. While the rate of HPV cervical cancer has diminished in the United States over the past several years, likely due to the utilization of the HPV vaccine, it is still a preventable malignancy that affects many women.

Pathophysiology:
There are two major types of cervical cancer: squamous cell carcinoma and adenocarcinoma. The most common type of cervical cancer is squamous cell carcinomas. Squamous cell carcinomas develop from squamous cells, which are thin in nature and line the outer portion of the cervix. Adenocarcinoma, on the other hand, is a glandular form of cancer that develops from columnar cells that line the canal of the cervix.

The majority of cases of cervical cancers are caused by the Human Papillomavirus (HPV). This virus occurs in nearly all women who are sexually active but is usually self-limiting. It is only in a few percent of the patient population exposed to this virus that cervical cancer will develop. The other form of cervical cancer, which is less prevalent when compared to cervical cancer caused by HPV, results from smoking. Smoking is a huge risk factor for a variety of cancers in a variety of anatomic locations within the body, and cervical cancer is no exception.

Cervical cancer that results from the HPV virus is dependent on a host of factors. The major factors that contribute to the resultant development of cervical cancer from HPV include strain type of the virus (certain HPV strains are more carcinogenic than others), compromised immune system, smoking and vitamin deficiencies. Patients who become sexually active at an early age and/or have increased number of sexual partners also face a higher risk of developing cervical cancer in the future. There have also been studies that have indicated a that there is a genetic component to the development of cervical cancer from HPV infection. Studies have suggested that women who have a family history of a first degree relative being diagnosed with cervical cancer are at increased risk (as much as 100% more) of developing cervical cancer at some point in their lifetime; as compared to those who did not have a family history of any first degree relative with cervical cancer.

While the genetic component does contribute to the risk of development of cervical cancer, it is still only associated with a small percentage of cervical cancer cases. Studies have suggested that the genes involved in apoptosis have been associated with the increased risk of cervical cancer. Those genes with a higher association include Tumor Necrosis Factor (TNF) and Tp53. These genes are important in gene repair and apoptosis. Other genes that have been linked to the development of cervical cancer include HLA anomalies, CCR2 (chemokine receptor-2) on chromosome 3p21 and the Fas gene on chromosome 10q24.1. These genes have been associated with increased susceptibility to the HPV virus that, when contracted, will over time develop into cervical cancer. Therefore, these genes do not cause cervical cancer; but rather, predispose patients to a higher likelihood of being infected with HPV, that may result in cancer in the future.

The HPV virus is composed of double-stranded DNA composed of 6 major regulatory proteins: E1, E2, E3, E4, E6 and E7; and two frame proteins L1 and L2. There are over one hundred different strains of the HPV virus. However, not all of those strains result or even predispose one to the development of cervical cancer. When patients with cervical cancer were evaluated, it was found that approximately 8 strains were the cause of cervical cancer. The high-risk strains that are the most common contributors to the development of cervical cancer include HPV type 16, 18, 31, 33, 35, 45, 52 and 58; with HPV type 16, 18 and 45 being the most common viral strains resulting in Cervical Adenocarcinomas. There are other HPV strains that are considered low risk and must be evaluated accordingly – to ensure that further development of less invasive, low-grade cancers are not present.

When the patient becomes infected with the HPV virus, the viral proteins begin to bind to proteins present within the body. For example, E7 binds to a protein called Rb protein, which results in its inactivation. E6 binds to p53 and breaks it down, causing Tp53 and Rb genes to lose their original function, which is to mediate apoptosis. Without mediation of apoptosis, there is an overproduction of cell growth after DNA is damaged. The uncontrolled cell replication results in mutated, cancerous cells that progress into cancer.

Patients who are immunodeficient because of certain diseases are at increased risk of developing viruses such as HPV that may progress to cervical cancer in the future. One major immunity compromising virus that can increase the risk of being infected with HPV is another sexually transmitted virus HIV (Human Immunodeficiency Virus). Studies have suggested that patients with HIV are 5 times more likely to contract HPV, that may progress to malignancy.