Grid Computing Cervical Cancer: January 2014

By Bryna Federspiel, Ashley McGuinness, and Elise Mitchell

In an effort to learn more about cervical cancer and aid research in this area, our group chose to participate in the project Mapping Cancer Markers, found on the World Community Grid. Cancer is a pressing problem worldwide. Currently, early and accurate detection is difficult, rendering treatment less effective. Cancer occurs when damage is done to cellular material, most importantly certain genes within a cell, causing uncontrolled cell growth. Mutations leading to cell malfunction and cancer can be detected in biological samples through indicators such as changes in DNA or proteins; combinations of these markers are unique to various forms of cancer, and individuals diagnosed with the same form of cancer may have different genetic mutations that require different treatments (Jurisica, Cumbaa, Tsay, & Kotylar). This project aims to use the grid to quickly and efficiently analyze data from biological samples from both cancer patients and controls in order to identify multifarious cancer markers. Researchers believe identifying unique cancer markers in various forms of cancer and comparing samples between cancer patients and controls will lead to earlier detection, identification of high-risk patients, and both individualization and optimization of cancer treatments (Jurisica, Cumbaa, Tsay, & Kotylar). Through this project, researchers also hope that markers will be used to lead to more effective treatments for other diseases (Jurisica, Cumbaa, Tsay, & Kotylar).

For more information on grids, see http://www.worldcommunitygrid.org/research/mcm1/overview.do

Cervical (or uterine cervix) cancer is a cancer of the tissues of the cervix, which is the organ that connects the vagina to the uterus (see figure 1 below for the anatomy of the female reproductive system). It is almost always caused by a previous infection of human papillomavirus, or HPV. There are over 150 HPVs, and more than 40 are transmitted during sexual contact (NIH 2013). This sexually transmitted disease (STD) is the most common STD in the United States, with 42.5% of women having genital infections (NIH 2013). Low-risk HPVs are those that do not cause cancer, but high-risk HPVs do; types 16 and 18 are the most deadly. These high-risk HPVs are responsible for 5% of cancer worldwide, but some infections can go away within 1-2 years and be asymptomatic (NIH 2013). However, some type of HPV causes 70% of all cervical cancer cases (NIH 2013). HPV infects cells of the epithelium, transcribes its RNA into proteins, and two of these proteins interfere with normal cell function. This makes the cell grow uncontrollably and avoid apoptosis, or spontaneous cell death. These infected cells grow and mutate at a high rate. This leads to high rates of mitosis and tumors in the cervix (NIH 2013).

HPV causes hyper proliferative lesions (warts) on infected epithelial surfaces, either mucosal surfaces or keratinized epithelium. It replicates in stratified squamous epithelium. This virus is in the family Papillomaviridae and has unenveloped, circular, double-stranded DNA. It is expressed after the epithelial tissue completes a replication cycle. It begins in the basal epithelial cells and the infected cells are pushed to proliferate faster by non-structural viral proteins in the basal layer. The genome of the virus is now replicated. The epithelial cells ascend as they mature and the viral genes are expressed. In later stages structural viral proteins continue to be produced. Our immune system can sometimes fight off these infections, however, if the virus does not go away, it can eventually cause cervix cells to change and become pre cancer cells. These pre cancer cells may either turn into cancer or return to normal. See figure 6 for an electron micrograph photo of HPV.

Scientists are now stating that it can take 10-20 years after an initial infection of HPV for a cervical tumor to form (NIH 2013). Practicing safe sex using condoms is a way to reduce the transmission of HPV. There have been two HPV vaccines approved by the Food and Drug Administration (FDA). Gardisil® is shown to prevent cervical, anal, vulvar, and vaginal cancers, as well as preventing the warts caused by HPV. Cervarix® is strictly to protect against cervical cancer (NIH 2013). Besides HPV, other risk factors for cervical cancer include having many children, having multiple sexual partners, smoking, using birth control pills, being immuno-compromised, or having sexual intercourse for the first time at a relatively young age. Signs of cervical cancer include vaginal bleeding or unusual discharge, pelvic pain, or pain during intercourse (NIH 2013).

It is important to get regular Pap smears since there are usually no signs or symptoms of early cervical cancer, and these tests can detect any cervical cell abnormalities. The vagina is opened with a speculum during the Pap smear, thus exposing the cervix. From there, the physician swabs the cells of the cervix with a cervical brush. These cells are placed into a small container of preservative and sent to the lab for analysis. Most guidelines now say that women should receive their first Pap smear at or before age 21. Women ages 21-29 should be screened every 3 years following normal results of the initial Pap smear. Women ages 30-65 should be screened every five years, again barring any complications (NIH 2013).

Treatment of cervical cancer varies depending on the whether the cancer cells have invaded other parts of the body. This happens if the cancer has spread to nearby tissue, if it has gone to the lymph nodes, or if it has hit the bloodstream. Stage 1 cervical cancer means that the cancer has not grown past 5 millimeters deep and 7 millimeters wide (see figure 2). Stage 2 cervical cancer implies that the cancer has spread past the cervix, but it has not yet hit the pelvic wall (see figure 3). Stage 3 cancer means that the disease has spread to the pelvic wall, has become large enough to block the ureters, and is causing kidney problems (see figure 4). Stage 4 means that the cancer has spread to the body parts away from the cervix (see figure 5). Treatment includes chemotherapy, radiation, hysterectomy, and/or surgery to remove tumors (NIH 2013).