The Human Papillomavirus, shortened to HPV, consists of numerous strains of the virus that each posses different cytopathogenic effects. These cytopathogenic effects differ between sexes but the severity of some of the strains can even lead to multiple types of cancer due to a lack of preventative measures. This DNA virus has a life cycle divided into multiple phases, and effectively uses these phases to disrupt host cell replication and ultimately lyse the cell in order to further spread through the host. The ability of the virus to establish cancer depends on the ability of the sever strains to integrate into the host genome and begin to rapidly divide. Although this process is fairly common for most cancers, the fact that we can ultimately prevent this process from occurring is one economical and social issue that needs to be resolved in favor of developing enough knowledge of the vaccine to begin mass implementations of it.
Residing in the Baltimore Class 1 due to its circular double stranded DNA genome, the small non-enveloped Human Papillomavirus is efficient at infecting mucosal and epithelial cells of the body. The virus searches for desirable non-differentiated basal cells to attach and begin its life cycle in the host cell. This attachment occurs by means of the cellular receptor α6-integrin. In its 8,000 base pair genome, the minor capsid protein L2 claims a majority of the functions in the replication and life cycle of HPV (Pereira 187-197). However, the key players in the infection and spreading of the virus are the E6 and E7 proteins. The other proteins are E1, E2, E4, E5, and L1. The structure of the human papillomavirus contributes to the differing effectiveness and severity of the numerous strains of the virus, while the life cycle remains consistent.
The lack of variance in the reproduction and replication of HPV allows this aspect of the virus to be easily studied. The virus begins by locating desirable basal cells of differentiating epithelial cells of the epidermis in the human host and attaching to the cellular receptor α6-integrin. The basal cells are desired by the HPV infection since their main function is to divide. This non-enveloped DNA virus undergoes receptor mediated entry through endocytosis. Since the virus lacks an envelope, the DNA directly enters the nucleus to undergo transcription. Transcription is separation between early and late gene transcription with late gene transcription occurring after DNA replication. Early gene transcription produces the multiple viral proteins used throughout the life cycle, and initiates the proliferation of the basal cells. The virus accomplished this proliferation due to its essential and highly effective E6 and E7 proteins. These proteins are successful at inhibiting and inactivating certain anti-oncogenes whose functions are controlling cell proliferation. E6 is associated with the demise of p53, while E7 contributes to the disruption of the functions of Rb. Rapid cell division begins, leading to the warts associated with human papillomavirus. The transcriptions of these proteins in a high-risk HPV infection result in far worse outcomes such as cancer (Nees 4289-4298). Following early gene transcription, DNA replication occurs with the assistance of host enzymes such as host DNA Dependent DNA polymerase. HPV differs compared to other DNA viruses: the DNA replication process consists of several phases. The first phase yields very few viral DNA as the basal cells begin to differentiate into keratinocyte. Following the maintenance of the first amplification of the basal cells, a second amplification occurs. Late genes become transcribed and expressed as the viral DNA is finally made. The capsid proteins formed by the late gene transcription assist in the assembly of the virus in the nucleus. To exit the cell, HPV uses the process of cell lysis to destroy the host cell and spread to surrounding cells.
After the life cycle is completed, the severity of the disease relies on the specific strain a person contracts. The different types of diseases associated with HPV are directly related to the different strains. There are around 130 strains with the more severe strains being transmitted by the genitals and divided between “low-risk” and “high risk” HPV types. The low-risk types of HPV consist of such symptoms as genital warts, while the high-risk types of HPV can cause cervical cancer. The cytopathogenic effect (CPE) of the virus depends on the strain. For most strains, multiple types of warts can be found including plantar warts, skin warts, flat warts, and the severe yet common genital warts. HPV can be transmitted by sexual contact, vertical transmission, or simply contact with an infected person. The more severe strains of HPV can cause several cancers including not only cervical, anal, and penile cancers but also oral/esophageal cancers from sexual acts such as oral sex. For women, the most severe strains that can lead to cervical cancer are HPV-45, HPV-18, HPV-31, and HPV-16. The ability for one strain of HPV to cause cancer and the inability in another is due to the ability of a strain to integrate the host genome. This integration leads to uncontrolled cell growth and ultimately metastasis to other areas leaving no original host tissue. If the host body is able to clear the HPV infection, the host can no longer be infected with that strain of HPV. Unfortunately, this protection does not extend to all the other strains of HPV leaving the host susceptible to multiple HPV infections.
Thanks to current medicine, there are available vaccines for this virus. For the less threatening warts, most will clear on their own. Otherwise, there is an available option of allowing your doctor to freeze or physical remove your wart. It is recommended that these procedures be done by a doctor since all viral cells must be removed in order to rid the host of the virus; failure to do this will result in another outbreak. Another approach would be to obtain one of the two widely known vaccines known as GARDASIL and CERVARIX. GARDASIL is said to help protect young women and men ages 9-26 against 2 types of HPV against 90% of genital warts. Women are also protected against two additional HPV strains associated with causing 75% of cervical cancer (3). CERVARIX is designed for women against the two cervical cancer causing strains HPV-16 and HPV-18 (4). These vaccines are the most effective for preventative measures but should not be the only form of precaution. A person should also avoid scratching at warts, wear condoms, avoid smoking as well as obtain the necessary HPV tests for woman including an annual PAP, or Papanicolaou, smear. Obtaining an annual PAP smear by a gynecologist, allows the doctor to effectively determine if any abnormal cells or growing. The use of this procedure has greatly decreased the severity of HPV.
The epidemiology of this virus is not only shocking but large enough to impact a majority of the population at some point in their life. Today, nearly 20 million Americans have an HPV infection with that number increasing yearly by six million. Statistics show that at least half of the sexually active population will become infected with the virus at some point in their life (CDC). Gay and bisexual men as well as the immune compromised tend to have a higher risk of HPV health related problems. However, the most susceptible people are the highly sexually active population, usually young adults. Due to this fact, many programs need to be implemented to inform them of the dangers of unprotected sex. School policies on health education need to be reformed to veer away from “abstinence only” teachings and start elaborating on the precautionary steps to avoid viruses such as these. This gap in education is where many economical and social issues arise with not only health education with the vaccine itself. Many states have been attempting to pass legislation to mandate the HPV vaccine in their school systems. Since the vaccine has been wrongly dubbed as a safe sex vaccine, many parents are outraged and refuse to give their younger children the vaccine. Although most states included an “opt-out” clause in their bills, this legislation has yet to be passed. These misinformed parents are a prime example as to why more people need to be educated on not only the vaccine but the virus itself. This would enable a decrease in the gap in the social issues with the vaccine.
The effect of the non-enveloped circular double-stranded DNA Human Papillomavirus on our society is an issue everyone should be concerned with. According to the CDC, HPV is the “most common sexually transmitted infection (STI)” (CDC). Therefore, the available precautions need to be implemented on every capable person not just for their benefit but for the benefit of the population. Although some people argue that the risks associated with obtaining the vaccine are too dangerous, the FDA would not approve a vaccine that was any more harmful than any other vaccine. Even though people react differently to different vaccine, my sister and I along with many other people I know have received either the Gardasil or Cervarix vaccine with little to no side effects. Therefore, I believe the media is misinforming and scaring the public into false conclusions. Such preventative measures as lowering the amount of yearly cancer cases should be enough to motivate people to at least help themselves. Although genital warts can only lead to cervical cancer in women, young men can do their part in becoming vaccinated if not to stop the spread of the virus but to also prevent themselves from obtaining anal or penile cancer.
Pereira, Ramon, Hitzeroth, Inga I., and Rybicki, Edward P. "Insights into the role and function of L2, the minor capsid protein of papillomaviruses ." Archives of Virology 154.2 (2009): 187-197. Web.28 Mar 2010.<http://www.springerlink.com/content/r043674871302887/>.
Nees, Matthias, Geoghegan, Joel M., Munson, Peter, Prabhu Vinayakumar , Liu, Yun, Androphy, Elliot, and Woodworth, Craig D."Human Papillomavirus Type 16 E6 and E7 Proteins Inhibit Differentiationdependent Expression of Transforming Growth Factor-b2 in Cervical Keratinocytes." Cancer Research 60. (2000): 4289-4298. Web. 29 Mar 2010. <http://cancerres.aacrjournals.org/cgi/reprint/60/15/4289>.
“Genital HPV Infection - CDC Fact Sheet.”(2009). 29 Mar 2010. <http://www.cdc.gov/std/HPV/STDFact-HPV.htm>.