HPV is a closed circular double-stranded DNA non-enveloped virus. Genetically, it’s stable and biologically had not changed for 200,000 years (Galani et al.2009). They belong to the papillomaviridae family hence their characteristic in attraction to the basal layer of cutaneous or mucosal epithelia in humans. HPVs are tissue-specific can infect skin, cervix, vagina, anus, vulva, head of the penis, mouth, and throat. Over 100 types of HPV had been identified. Theses can further be divided into two tropism groups: skin infecting or cutaneotropic and mucosal infecting or mucosotropic. Generally, HPVs belong to genus beta, gamma, Nu and Mu are cutaneotropic and those belong to alpha are mucosotropic. (Mistry et al.2008).
Alpha palliomavirus genus contains high-risk and low-risk members that mainly infect the cervical area. Its high risk members such as HPV16 and HPV18 are cancerous that frequently been identified with cervical cancer. Its low-risk members are associated with external genital warts such as HPV6 and HPV11. Few alpha palliomavirus are cutaneous such as HPV2 which causes common warts in kids. Beta palliomavirus is the most widespread. Most people are infected to this virus early on in life. They can be asymptomatic and had been associated with the development of non-melanoma skin cancer. Gamma, Nu and Mu HPVs cause skin warts that do not lead to skin cancer such as verrucas and palmar warts (Doorbar 2007).
For an infection to occur, a lesion in the epithelial cells layer is required. Once these lesions occur, the virus must infect the resulted epithelial stem cells. For example, cutaneous beta virus can infected the stem cells of hair follicles when a hair is plucked. Mucosal sexually transmitted alpha virus such as HPV16 infects columnar cells of the transformation zone in female genital (Doorbar 2005). L1 major and L2 minor are the capsid proteins of HPVs. They bind to the heparin sulfate polysaccharides on the cells’ surface. This enables cells’ uptakes of the virus via vesicles (Galani et al. 2009).
Once entering the cells, virus uncoats and its DNA enters the nucleus. HPVs do not infect cell to cell. After initial infection, the virus maintains its genome as an episome during host cells’ replication. HPV infected cells will divide more rapidly without differentiation until it reaches from the deepest epithelial basement layer to the superficial outermost layers. HPV genomes divide with it (Doorbar 2005).
Viral genome can encode a total of 8 proteins in type E for early or L for late. Only E proteins are made until it reaches the superficial epithelial layer, then L2 and L1 will be expressed also. Protein E1, E2, E4 and E5 are responsible for maintaining the genome during hosts ‘cell division such as keeping it separated from the host’s genome, and enhance reproduction of viral genome and keep them in low copies. Its other proteins E6 and E7 facilitate host cells’ division and prevent host’s apoptosis. Because of their functions, E6 and E7 are oncogenes that cause cancer. L1 and L2 are the capsid proteins that only express when it’s time for virion packaging. By the time PHV infected cells reach the upper layers of epithelial, the virus take over the host, and make large number of its own genome. The host cells died after virions are packaged and they’re released to the environment. Its survival enhanced if released by cornifying the superficial epithelial layer. This general outline of HPV’s life cycle is followed in all genuses (Doorbar 2005).
E7 and E6 are the major players in causing cancer. E7 binding to tumor suppress gene Rb and cause out of controlled cell division. E6 bind to p53 which prevent cell division in infected or damaged cells and inactivated it. These two genes are very effective in cancer causing HPV16 and HPV18. In tumor cells, HPV life cycle will not complete hence their ability to keep the host dividing (Doorbar 2005).
In cervical cancer, infected sites do not resolve and lesion is maintain which led to CIN1 stage of cervical lesion. CIN1 stage can lead to CIN2 and if reach CIN3 can ultimately cause cancer. Oral cancer cause by HPV is very similar (Scully 2002).
Scully, Crispian "Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about possible sexual transmission." Oral Oncology 38.3 (2002): 227. Academic Search Complete. EBSCO. Web. 2 Dec. 2009.
Galani, E., and C. Christodoulou "Human papilloma viruses and cancer in the post-vaccine era." Clinical Microbiology & Infection15.11 (2009): 977-981. Academic Search Complete. EBSCO. Web. 2 Dec. 2009.
Mistry, Nitesh, Carl Wibom, and Magnus Evander. "Cutaneous and mucosal human papillomaviruses differ in net surface charge, potential impact on tropism." Virology Journal 5.118 (2008).PubMed Central. Web. 02 Dec. 2009.
Doorbar, John "Papillomavirus life cycle organization and biomarker selection." Disease Markers 23.4 (2007): 297-313.Academic Search Complete. EBSCO. Web. 2 Dec. 2009.
Doorbar, John "The papillomavirus life cycle." Journal of Clinical Virology 32.(2005): 715. Academic Search Complete. EBSCO. Web. 2 Dec. 2009.