How Human Papilloma Virus Causes Cancer - Coursework Example

How HPV causes cancer? Introduction: Most of cancer cases that exist in the world happen because of viruses. Both DNA and RNA viruses are able to cause cancer in humans. One of the DNA viruses is Human papilloma virus (HPV)(Liao, 2006), which belongs to the family of papoviruses, non-enveloped, double stranded DNA viruses (Levinson and Jawetz, 2000) figure 1. Human papillomavirus were discovered after cottontail rabbit papillomavirus (CRVP). The first investigation of HPV in human cancer was conducted in 1970s, particularly in patients with epidermodysplasia verruciformis. (Howley, 2006). HPV usually causes benign papillomas or warts in humans (Liao, 2006). These viruses can also affect humans worldwide, especially women as they are susceptible to acquiring cervical cancer (Schiffman et al., 2007). Most studies consider these viruses as a major cause of cervical cancer. Also, these studies have identified the mechanism of cervical cancer development (Schneider, 1993; Boulet et al., 2007; Schiffman et al., 2007). This can explain the progression of disease. Most, if not all cases of cervical cancer occur due to the persistent infection of HPV, particularly the HPV-16 (Liao, 2006). Furthermore, HPV can be divided into several types and species such as HPV16, 18, 31, 33, 35, and 39 (Zur Hausen, 1999). Specific types of HPV linked with cervical cancer are HPV16, 18, 31 and 45 (Chumworathayi et al., 2010). The genome of the virus can encode several proteins such as (E1, E2, E4, E5, E6, E7 and E8) and two capsid proteins (L1, L2). This classification depends on the types of HPV (Su et al., 2010). Cervical cancer requires particular genes to be developed, such as E6 and E7 as Boulet and his colleagues have found (Boulet et al., 2007) and that have been encoded by HPV (Howley, 2006). Once HPV enters epithelia cells and integrates in the host DNA, the malignant transformation increases by the E6 and E7 production (Liao, 2006). These genes have effects on cell cycle progression in cervical cancer. However, HPV can also play a role in aggravating other forms of cancer in humans such as head and neck tumor and skin cancers in immunocompromised individuals (Liao, 2006). Apart from cervical cancer, HPV can also cause cancer according to HPV diversity both in humans and animals. Examples are the cottontail rabbit papillomavirus (CRVP) infection in domestic rabbits, epidermodysplasia verruciformis patient HPV5, 8, 14, Bovin paoillomavirus type 4 (BPV4), alimentary tract cancer in cattle, and Bovin papillomavirus type 1 in horses (Howley, 2006). As several studies observe the association between HPV and cervical cancer, this essay aims at discussing cancer development caused by HPV. Transmission and infection of HPV: Human papillomavirus can be transmitted in different ways both sexually and non-sexually. However, the most common transmission happens through sexual intercourse. This causes anogenital warts of type (6 and 11 HPV) which are considered low in risk with respect to many HPV types. Other types of cervical cancer such as HPV16, 18 are responsible for about 70 % of cervical cancer and 50 % of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3) (Schiffman et al., 2007; Smith et al., 2007). The HPV16 and 18 are considered as high risk types of HPV. Additionally, infection of HPV is usually transmitted by direct contact such as skin to skin and mucosa to mucosa, nevertheless, the likelihood of infection for each sexual intercourse is still unknown. Furthermore, several types of HPV can be transmitted collectively according to high proportion of infected women. On the other hand, men also may be infected by different types of HPV, therefore, any sexual act can quickly result in the transmission HPV types (Schiffman et al., 2007). In case of non sexual transmission, a child can acquire the infection of HPV from the mother (Castellsague et al., 2009) especially by placenta as Rombaldi and his colleagues have observed. For example, transmission from mother to the child may occur via amniotic fluid and fetal membranes (Rombaldi et al., 2008; Smith et al., 2010). In one study, it was found that infection of HPV can develop either genital warts or cervical cancer, with possible regression of HPV infection, genital warts and grades of CIN1-3. Only cervical cancer involves the risk of mortality as shown in figure 2 (Insinga et al., 2009). Consequence of infection: The infection of HPV produces papilloma and this coan lead to different effects; one of them is persistence with virus following this neoplasia which leads to cancer. In this paper, cervical cancer is the focus of discussion because it is the second most common malignity in women that leads to death worldwide (Brinkman et al., 2005; Boulet et al., 2007). Another effect is HPV clearance, which occurs when the infection remains constant in the infected area. Therefore, it may regress gradually because of the immune system within 12 months or even, in some cases, two years after the preliminary infection (Schiffman and Castle, 2003; Chumworathayi et al., 2010). Development of cervical cancer: Cervical cancer can be divided into two main types; squamous cell carcinoma (SCC) and adenocarcinoma. The former is related to roughly 90% to 95% of the cases of cervical cancer. The abnormality of cell growth in the cervix is known as cervical intraepithelial neoplasia (CIN) (McIndoe et al., 1984). CIN is classified into three grades according to abnormal category; CIN1, CIN2 and CIN3. For instance, CIN1 is categorised as a mild grade of dyskaryosis or low-grade squamous intraepithelial lesions (LSIL). CIN2 is a moderate grade and finally, CIN3 is a severe dyskaryosis. CIN2-3 is called high-grade squamous intraepithelial lesions (McIndoe et al., 1984; Chumworathayi et al., 2010). Nonetheless, women with CIN3 are not necessarily at risk of acquiring cervical cancer. It can not be said that they will continue to develop cancer (McIndoe et al., 1984). These grades of cervical cancer can be observed in young women aged between 30 and 40 years (Denny et al., 2005)(Blumenthal et al, 2005). Several studies have divided cervical cancer development process into three main steps; viral infection, persistence and cell transformation and invasion as shown in Figure 3 (Schiffman and Castle, 2003; Khan et al., 2005; Schiffman et al., 2007). In the first step, viral infection includes attacking the skin by virus and the viral entrance into epithelial squamous. In persistence stage, infections disappear or get suppressed by the immune system especially in young women within the first year. If the infection continues to increase for long, cervical intraepithelial neoplasia may occur. In the final step, invasion can be observed after a long period of infection (ibid). The mechanism of invasion of virus is important to understand these steps clearly. To begin with, virus starts the infection by breaching the skin or mucosa. Host epithelial cells are infected by HPV as long as this virus remains inside, these epithelial cells enable the HPV to produce new viruses. During progression of infection, some infected cells are regressed and the viral particles are released. Viral DNA of the host genome can incorporate high risk types of HPV, which is not considered a normal part of the life cycle. The incorporation of virus may lead to a long time infection. Furthermore, the longer infection period provides the opportunity for cancer to develop (Hamid et al., 2009). There are two main viral genes for the HPV ability to cause cancer; E6 and E7. In addition, each of them has a role in cancer development. E6 can inhibit the protein that is responsible for preventing cancer and cellular stress types such as DNA damage and viral infection. This protein is called p53. Without this protein, a cell keeps dividing (Jabbar et al., 2010). E6 can also activate telomerase, when this protein exists, telomerase retains the chromosomes end. This avoids chromosomes collapse and facilitates proliferation of cancer cells (Oh et al., 2001; Hamid et al., 2009). Whereas E7 can inhibit retinoblastoma protein (Rb), which serves to suppress the progression of cell cycle by preventing transcription factor activity (Munger and Howley, 2002). E6 and E7 combination plays a key role in the productive cell cycle that can lead to developing cancer (Figure 4). (Jabbar et al., 2010; Moody and Laimins, 2010). In addition to E6 and E7, there is also E2. All these genes are important due to their roles in cervical cancer development. E2 binds to both the E6 and E7 proteins. Once E2 is binding, it can activate or block transcription of E6 and E7 (Webster et al., 2000). Moreover, without binding E7 by E2, E7 joins Rb. As a result of this, Rb cannot function normally. E2 has a transcription factor (E2F) that facilitates the cell cycle. So, binding this E2F to Rb prevents E2F from playing its role as a transcription factor. Consequently, the cell division does not progress. However, binding of E7 to Rb can prevent E2F from binding Rb. So it can act as a transcription factor. An important step in cancer development is when a cell synthesizes E7 protein and when E2F causes a cell division. It can be concluded that E6 and E7 are the critical proteins in HPV cell division and play a big role in promoting the development of cancer (Moody and Laimins, 2010). Prevention and vaccination: It is important to prevent HPV before it infects the epithelial cells by obtaining antibody response which serves to counteract the particles of HPV. The L1 protein can facilitate the vaccination process because it plays a key role in neutralizing antibody production. It has been observed that L1 expression in different cell types conducts similar virus-like particles (VLPs) as the original virions in terms of morphology and immunology of these virions (Su et al., 2010). Vaccination with HPV L1 VLPs has been shown to induce high neutralizing antibodies titers both in the animal models and humans (for review, see (10)). There are two novel preventive vaccines, Gardasil and Cervarix. The former Gardasil is derived from four types of HPV (6, 11,16 and 18), this vaccine is known as a quadrivalent L1 virus-like particle (VLP) recombinant vaccine .Whereas, the latter is an L1 VLP vaccine taken from HPV types 16 and 18. These vaccines can function perfectly well because they target the high risk types of HPV. This essentially means that they can protect almost 80% of cervical cancer because they can also play their role as a protective vaccine against other types of viruses related to cervical cancer such as HPV-31 and 45 (Su et al., 2010). It is noticeable that vaccines target specific types of viruses and not all types. However, two new vaccines are important to protect against cervical cancer. In addition, vaccination is one of the crucial approaches to prevent cervical cancer. The detection of HPV genotypes caused infection is also important to prevent the prevalence of cervical cancer in women worldwide. Thus, screening is one of the methods that are used to detect the infection with carcinogenic HPV types. (Wheeler et al., 2009). Conclusion This essay has aimed to cover several aspects of HPV and the importance of cancer development mechanism especially in women. HPV is one of the etiological factors for cancer development and it has specific mechanism through which it causes the disease. There are different types of viruses to exacerbate the cancer such as HPV-16 and 18. The severity of disease depends on the virus types. The infection of this virus can be transmitted both sexually and non-sexually. The consequences of the infection can be negative and can be noticed by observing the clearance of infection. In the other cases, the consequences are positive in which case, virus exists and causes neoplasia that leads to cancer. Cervical cancer has a complex mechanism through which it develops and occurs through specific HPV genotypes. Several studies have tended to find therapeutical approaches to prevent the infection and cancer whether immunologically or clinically. Some of their findings have observed novel vaccines but they are preventive vaccines meant for specific types of viruses. Therefore, there is an extreme need for the development of effective therapeutical vaccine that can target all types of HPV. Further studies may to provide more information about HPV vaccination. Figure 1. The shape of Humanpapilloma virus (Levinson and Jawetz, 2000). Figure 2. The development of infection by HPV leads to genital warts and cervical cancer, this diagram illustrates the three grades of CIN and the effect of each of them (Insinga et al., 2009). Figure 3. the infection by HPV and its consequences, location and period of infection is also shown in this picture. (Schiffman and Castle, 2003; Khan et al., 2005; Schiffman et al., 2007). Figure 4. 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