HPV as a Cancer
The Dangers of HPV
How do People Get HPV?
HPV is transmitted through intimate skin-to-skin contact. It's the most common sexually transmitted infection. It's also spread through contact with infected genital skin, mucous membranes, or bodily fluids, and can be passed through intercourse and oral sex.
Anyone who is sexually active can get HPV.
- Genital warts- They can be raised, flat, pink, or flesh-colored. They can even be shaped like cauliflower.
- Sometimes there is a single wart; other times multiple warts appear.
High-Risk HPV can cause can cause Cancer
- Cervical cancer: Virtually all cases of cervical cancer are caused by HPV, and just two HPV types, 16 and 18, are responsible for about 70 percent of all cases (7, 8)
- Anal cancer: About 95 percent of anal cancers are caused by HPV. Most of these are caused by HPV type 16.
- Oropharyngeal cancers (cancers of the middle part of the throat, including the soft palate, the base of the tongue, and the tonsils): About 70 percent of oropharyngeal cancers are caused by HPV. In the United States, more than half of cancers diagnosed in the oropharynx are linked to HPV type 16 (9).
- Rarer cancers: HPV causes about 65 percent of vaginal cancers, 50 percent of vulvar cancers, and 35 percent of penile cancers (10). Most of these are caused by HPV type 16.
- The two most important HPV genes in the development of cancer are E6 and E7. Both of these genes need to be on all the time in order for cancer to develop.
Since p53 is frequently a wild type in cervical cancers, unlike other cancers in which it is often mutated, the notion has arisen that E6's activity with respect to p53 is equivalent to an inactivating mutation of p53.
Telomerase/Telomerase in HPV
Telomere shortening results in chromosomal instability, subsequently leading to cancer development. Given that HPV16 can affect telomerase activity and telomere length, it's sconjectured that telomere length in peripheral blood lymphocytes (PBL) might affect the risk of HPV16-associated OPC and tumor HPV16 status in patients.
Stages of the Cell Cycle of HPV
- The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects
- Through the expression of E7 and E6 viral oncoproteins, certain HPV genotypes (high-risk HPV) block pRb and p53 cellular proteins and, thus, generate a state of unscheduled activation of the cell cycle and create a permissive state for the appearance of nonrepairing novel mutations and genomic instability.
- P16 is a tumor suppressor protein belonging to the family of INK4 cyclin-dependent-kinase inhibitors whose increased expression has been associated with HPV.
- The Rb protein is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth. -it has a central role in various differentiation processes, including eye, lens, brain, peripheral nervous system, epidermis, melanocytes, hair cells, muscle and liver.
DNA Repair Enzymes
The DNA damage response (DDR) plays a crucial role in the maintenance of genomic stability by coordinating cell cycle progression with DNA repair. The DDR is regulated by two main kinases, ATM and ATR (ATM and Rad3 related), that belong to the phosphoinositide-3.
Apoptosis and Checkpoints
- Apoptosis- is the process of programmed cell death (PCD) that may occur in multicellular organisms.
- Checkpoints- As a cell approaches the end of the G1 phase it is controlled at a vital checkpoint, called G1/S, where the cell determines whether or not to replicate its DNA. At this checkpoint the cell is checked for DNA damage to ensure that it has all the necessary cellular machinery to allow for successful cell division.
- To encode a short protein from the E8 gene.
- Effect of Human Papillomavirus on Cell Cycle–Related Proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in Precursor Lesions of Cervical Carcinoma. (n.d.). Retrieved from http://ajcp.ascpjournals.org/content/132/3/378.full
- (n.d.). Retrieved from http://www.nature.com/onc/journal/v25/n38/full/1209615a.html
- (n.d.). Retrieved from https://en.wikipedia.org/wiki/Papillomaviridae#E6
- HPV and Cancer. (n.d.). Retrieved from http://www.cancer.org/cancer/cancercauses/othercarcinogens/infectiousagents/hpv/hpv-and-cancer-info