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Explanation of the HPV virus

Oncogenic versions of the HPV virus

The most dangerous aspect of the human papilloma virus is its potential to cause cancer. A highly studied topic is HPV's ability to cause cervical cancer. Part of the normal cellular life cycle is regulated by two genes, Rb and p53. Rb segregates the transcription factors necessary for progression through the cell cycle. This means that the Rb prevents the cell from dividing until it has isolated enough proteins for cell division. The important protein which Rb segregates is E2F. This makes Rb a tumor suppressor gene/protein. It does not allow the cell cycle to continue until it has accumulated enough proteins, especially the E2F protein. When a cell is infected with HPV, the E7 gene binds to Rb so that the Rb releases E2F and the other proteins. This is a signal for the cell cycle to progress. As long as the E7 stays attached to Rb, the cell cycle will continue to happen, thus causing a cycle of uncontrolled cell reproduction, which is one of the definitions of a malignant cell.

The other gene HPV attacks with oncoprotein E6 is p53. Within a cell, p53 functions in response to DNA damage. When cell DNA is damaged, p53 stops cell division and directs the genes involved in DNA repair to correct the damage. If the DNA cannot be repaired, p53 then induces programmed cell death (apoptosis), ensuring that a damaged cell dies and does not reproduce. In cancerous cells, p53 is often found to be damaged or nonfunctional. This allows cells with damaged, or altered DNA to continue living instead of being destroyed. Viral E6 protein can bind to p53, and make it inactive. This allows the virus to take over the cell and reproduce itself, since the virally inhibited p53 cannot stop it, or begin the process of programmed cell death. The repeated replication of cells with incorrect DNA information is the beginning of malignant tumor formation. Along with blocking the cell's p53, the viral E6 protein activates telomerase, an enzyme that synthesizes the telomere repeat sequences. Activating this enzyme maintains a repeated cell cycle that continues to produce viral cells. This leads to malignancy as the mutant cells continue to reproduce out of control.

The two most harmful and cancer causing human papilloma viruses are HPV 16 and HPV 18, (though 9 in total out of about 130 versions are confirmed oncogenic versions and another 6 are highly suspect of being so). Both of these are genital viruses which are spread through sexual contact. These types of the human papilloma virus have E6 and E7 proteins with very strong binding capabilities. This allows HPV 16 and HPV 18 to reproduce quickly and in great numbers, leading to uncontrolled reproduction of viral cells, and eventually cancer. It is well established that HPV 16 and HPV 18 are causative factors in cervical cancer, and now HPV16 is also an identified cause of oral cancer. A study done by Dr. No-Hee Park showed that the mouth was, at the cellular level, structurally very similar to the vagina and cervix. Both organs have the same type of epithelial cells that are the target of HPV 16. The majority of oral cancers are cancers of epithelial cells, primarily squamous cell carcinomas, not unlike the cancer that affect the cervix. This first step in understanding the similarities of these tissues and the disease that affects them, led to research that was able to link oral cancers to HPV. Dr. Park's study also showed that smoking and drinking alcohol help promote HPV invasion. Alcoholic beverages contain ethanol alcohol, and ethanol is known to inhibit the production of the p53 protein. The carcinogens in tobacco have been shown to damage cell DNA, the precursor event to malignancy. More recent work seems to indicate that the relationships between tobacco alcohol and HPV are additive in their effect as opposed to synergistic. This means that one factor alone (tobacco OR HPV) can be enough to begin the cascade of cellular events that culminate in a cancerous cell. In the oral environment it is HPV16 that we are concerned with.

A study conducted by the Johns Hopkins Oncology Center in 1999 and peer review published, furthered the premise that HPV is linked with certain types of oral cancer. Dr. Maura Gillison was the head of a study which tested 253 patients diagnosed with head and neck cancers. In 25% of these cases, the tissue taken from tumors was HPV positive. HPV 16 was present in 90% of the HPV positive tissues. This information helps to confirm that there is a strong link between HPV and oral cancer. Other important information came from subsequent studies.

There is a survival advantage that HPV+ oral cancer patients have over patients that come to the disease from other etiologies. Given that treatments for oral cancers at this time are the same regardless of the etiology which brings a patient to the disease, it seems logical to conclude that this survival advantage has something to do with the HPV positive tumors being more susceptible and vulnerable to the radiation treatments than their tobacco induced counterparts. It is possible that in the future clinical trials will be conducted that will establish some different treatment protocol for HPV+ oral cancers.


General information about viruses

Misunderstanding commonly results when people group viruses and bacteria into the same category of disease. Bacteria and viruses are two completely different organisms, each functioning in different and unique ways. Bacteria are one-celled organisms capable of living and reproducing independently. The major parts of a bacterium cell are; a cell wall, cytoplasm, and a nucleoid. The cell wall protects the cell and gives it shape. The cytoplasm is the fluid inside the cell where cell growth, replication, and metabolism are carried out. The cytoplasm also contains all the components for these actions such as the nucleoid, ribosomes, and plasmids. The nucleoid is the region in the cytoplasm where the strands of DNA are located. Bacteria cells reproduce through a process called binary fission. In this process, a single bacterium cell grows to twice its normal size and splits into two daughter cells. These two new daughter cells are exact copies of the original cell. When bacteria infect a body, they do so by multiplying inside the organism and producing toxins that infect surrounding cells or tissues. But very few bacteria are harmful. 99% of the bacteria found in the body are helpful, and most are actually necessary for life. Harmful disease-causing bacteria can be eliminated or killed with antibiotics.

Viruses on the other hand, exist and function in an entirely different manner than bacteria. They are not an independent organism. When a virus is alone it is not metabolically active like bacteria; it needs a host cell to function, and in which to reproduce. A virus is composed of only a protein capsule that encloses its DNA or RNA. When a virus comes in contact with a cell, it is capable of inserting its genetic material into that host cell. Once the virus has invaded a host cell, it can go into two phases: lysogenic or lytic. During the lysogenic phase, the virus remains dormant in the cell and does not affect the host cell,(Episomal virus) and is not in the process of converting it into a malignancy. The host cell continues to function normally, even though the virus has invaded it. During the lytic phase, the virus takes over the host cell and uses it to reproduce more viruses which will infect mor cells.

How a virus takes control of a cell, and treatment for some virus types

Once in the lytic phase, the virus's genetic material takes over the cell functions and controls the reproduction process. The viral genetic material orders the host cell to produce proteins and copies of viral DNA or RNA. The viral proteins then assemble into protein coats, and the viral DNA or RNA is packaged inside the coats. This produces many more viruses inside the host cell. When this reproductive process is complete, the host cell dies and the newly produced viruses are released to infect other cells. Unlike bacteria, a virus cannot be destroyed with antibiotics. Although there is currently no medical cure to eliminate a papilloma virus infection, the squamous intraepithelial lesions (SILs) and warts these viruses cause can be treated. When speaking of lesions that occur outside of the mouth, methods used to treat SILs include; cold cautery (freezing that destroys tissue), laser treatment (surgery with a high-intensity light), LEEP (loop electrosurgical excision procedure, the removal of tissue using a hot wire loop), as well as conventional surgery. Similar treatments may be used for external genital warts. In addition, two powerful chemicals (podophyllin and trichloroacetic acid) are capable of destroying external genital warts when applied directly to them. Imiquimod cream has also been recently approved by the Food and Drug Administration (FDA) as an effective drug treatment. Imiquimod works by stimulating the immune system to fight the virus. Once infected with a virus, it may become part of the organism/individual indefinitely, though it is poorly understood now if HPV enters periods of dormancy perhaps even for decades, or if the immune system destroys it and constant reinfection takes place since the virus is so common in our society. While there may not be outward signs of its presence, it can be present. A common example of this behavior can be seen in the herpes simplex virus that causes the cold sores on your lip. This virus lives on the ganglion of the nervous system permanently once infected, and only manifests itself occasionally, perhaps as the immune system becomes compromised through stressors or other mechanisms.

•••If you are a doctor that wishes to have tissue samples tested for HPV, or a patient that wishes to provide information to your doctor on where this can be done with accuracy; OCF recommends that you have the testing done by Johns Hopkins Medical Laboratories. They have a great deal of expertise and experience. The directions on how to contact them or where to send samples to are located at this link