Volume 31, Issue 1 (3-2024)
RJMS 2024, 31(1): 1-12 |
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Barzegar S, Teimourpour R. General Characteristics of Human Papillomavirus and the Emerging Need for a Vaccination Program against This Virus in Iran. RJMS 2024; 31 (1) :1-12
URL: http://rjms.iums.ac.ir/article-1-8095-en.html
URL: http://rjms.iums.ac.ir/article-1-8095-en.html
Department of Microbiology, School of Medicine, Ardabil University of Medical Science, Ardabil, Iran , r.teymourpour@gmail.com
Abstract: (374 Views)
Human papillomavirus (HPV) is the most prevalent sexually transmitted pathogenic virus in humans that causes benign warts and, in some cases, malignant tumors in cutaneous and mucosal epithelia in various parts of the human body, including cervical and anal cancers. HPV is a member of the Papillomaviridae family that has a double-stranded DNA genome. Since HPV cannot grow in tissue cultures, molecular hybridization assays are used for detection. The virus is classified into more than 200 types based on DNA sequences. In most cases, infections with this virus are asymptomatic and benign, and can be eliminated by the host immune system within 1-2 years. In some conditions, the immune system cannot defeat the infection, leading to chronic infection and ultimately malignancy. Cytology methods such as papanicolaou-stained smears are frequently used to monitor and detect precancerous and cancerous lesions in cervix cancer cases.
HPVs are typically divided into low-risk (LR) and high-risk (HR) types based on their ability to cause cancer. Infection with HR-HPVs that contain approximately 12 types is the most significant risk factor related to cervical cancer in women, along with oral mucosa, oropharynx, penis, vagina, and anal cancers. Studies have shown that genotypes 16 and 18 are the most prevalent types of HR-HPVs and responsible for close to 70 percent of cervical cancers. Furthermore, these types are related to other neoplasia, such as head and neck, and anal cancers. The most prevalent LR-HPVs are genotypes HPV-6 and 11, which are most frequently associated with anogenital warts and recurrent respiratory papillomatosis (RRP).
The main way that HPVs can easily spread is through skin-to-skin and skin-to-mucosal contact, and in order to infect a person, the virus must reach to the basal layer of the skin tissue. HPV uses its capsid proteins (L1 and L2) and heparan sulfate proteoglycans in the host cell to enter keratinocytes through endocytosis. In the first stage of infection, the virus uses E1 and E2 proteins and the replication machinery of the host cell to replicate and produce nearly 50–200 copies of virus particles. In chronic infections, HR-HPVs can integrate into the host genome, alter the normal cycle of cell replication, and lead to carcinoma. This is the key factor in the progression of infection to carcinoma. This integration leads to the overexpression of oncogenic proteins E6 and E7. These proteins have the main role in the progression of infection to malignancy. Protein E6 prohibits the blocking of apoptosis by binding to P53, while E7 deactivates retinoblastoma protein (pRB), which is necessary for suppressing the cell division cycle. These actions, along with some other circumstances, lead infected cells to transform into malignant cells.
HPV can evade the host immune system through the expression of its own proteins in the lower layer of the epithelium. Moreover, due to other factors including lacking viremia throughout its replication cycle, and lysing infected cells and escaping viruses only at the exterior layer of epithelium, it typically takes at least 2–3 years for the immune system to eliminate the virus.
HPV is one of the most common sexually transmitted infections, and 2–44 percent of women are infected with this virus. Cervical cancer ranks as the fourth most common cancer affecting women, displaying a notably elevated mortality rate, particularly in developing countries. Globally, around 90 percent of cervical cancer cases are attributed to Human Papillomavirus.. In Iran, the prevalence of infection ranges between 7 to 24 percent, and HPV infection is identifiable in approximately 78.8 to 79.3 percent of cases involving cervical cancer. . Due to the lack of specific treatment against the virus and the direct connection between persistent infection with HPV and cervical cancer, comprehensive and constant vaccination is essential for effective disease control. According to numerous studies, vaccination against HPV significantly decreases the incidence of cervical, nasopharynx, anal, vaginal, and penile cancer and also reduces the incidence of vaginal warts.
The available vaccines contain capsid protein L1 of the virus and prevent the entry of the virus into the host cells. Vaccines should be given at young ages before first exposure to the virus because they have no therapeutic benefit and have no impact on the emergence of persistent infections. Likewise, vaccination is the most efficient way to control cervical cancer, and there are currently three types of vaccines against HPV: Gardasil, Cervarix, and Gardasil 9. Gardasil, the first commercially produced vaccine, is a quadrivalent vaccine and confers protection against types 6 and 11, 16, and oncogenic types 18 of HPV. Cervarix is the bivalent vaccine and provides protection against types 16 and 18. To make vaccination more effective and prevent more cervical cancer, the nine-valent Gardasil has been produced. Gardasil 9, in addition to the types of Gardasil, contains an additional five types, including 31, 32, 52, 45, and 58, and is generally used in double doses to prevent a higher percentage of cervical cancer.
Infection with papillomaviruses is increasing, which has caused concerns in Iranian society, and it seems vital to have a widespread plan to control the infection. Preventing the spread of infection with the widespread use of vaccines at young ages and the diagnosis of infection in the primary stage is necessary to prevent the spread of infection and its transformation into cancer. Global vaccination programs have demonstrated a substantial decline in cancerous lesions associated with HPV types 16 and 18, with a reduction ranging from 90 to 100 percent. Moreover, the incidence of cervical cancer has decreased by 70 percent, and genital warts in women and men have seen reductions of 77 percent and 62 percent, respectively. Consequently, vaccination emerges as the most effective and economically feasible approach to cervical cancer prevention, particularly in developing nations. With an increasing number of cervical cancer occurrences and the undeniable connection between this cancer and HPV, there is an urgent need to set up a widespread vaccination program in Iran, where there is currently no comprehensive HPV vaccination program. This study summarizes the general knowledge and new findings of virology, pathogenicity, epidemiology, and vaccination of Human Papillomaviruses.
HPVs are typically divided into low-risk (LR) and high-risk (HR) types based on their ability to cause cancer. Infection with HR-HPVs that contain approximately 12 types is the most significant risk factor related to cervical cancer in women, along with oral mucosa, oropharynx, penis, vagina, and anal cancers. Studies have shown that genotypes 16 and 18 are the most prevalent types of HR-HPVs and responsible for close to 70 percent of cervical cancers. Furthermore, these types are related to other neoplasia, such as head and neck, and anal cancers. The most prevalent LR-HPVs are genotypes HPV-6 and 11, which are most frequently associated with anogenital warts and recurrent respiratory papillomatosis (RRP).
The main way that HPVs can easily spread is through skin-to-skin and skin-to-mucosal contact, and in order to infect a person, the virus must reach to the basal layer of the skin tissue. HPV uses its capsid proteins (L1 and L2) and heparan sulfate proteoglycans in the host cell to enter keratinocytes through endocytosis. In the first stage of infection, the virus uses E1 and E2 proteins and the replication machinery of the host cell to replicate and produce nearly 50–200 copies of virus particles. In chronic infections, HR-HPVs can integrate into the host genome, alter the normal cycle of cell replication, and lead to carcinoma. This is the key factor in the progression of infection to carcinoma. This integration leads to the overexpression of oncogenic proteins E6 and E7. These proteins have the main role in the progression of infection to malignancy. Protein E6 prohibits the blocking of apoptosis by binding to P53, while E7 deactivates retinoblastoma protein (pRB), which is necessary for suppressing the cell division cycle. These actions, along with some other circumstances, lead infected cells to transform into malignant cells.
HPV can evade the host immune system through the expression of its own proteins in the lower layer of the epithelium. Moreover, due to other factors including lacking viremia throughout its replication cycle, and lysing infected cells and escaping viruses only at the exterior layer of epithelium, it typically takes at least 2–3 years for the immune system to eliminate the virus.
HPV is one of the most common sexually transmitted infections, and 2–44 percent of women are infected with this virus. Cervical cancer ranks as the fourth most common cancer affecting women, displaying a notably elevated mortality rate, particularly in developing countries. Globally, around 90 percent of cervical cancer cases are attributed to Human Papillomavirus.. In Iran, the prevalence of infection ranges between 7 to 24 percent, and HPV infection is identifiable in approximately 78.8 to 79.3 percent of cases involving cervical cancer. . Due to the lack of specific treatment against the virus and the direct connection between persistent infection with HPV and cervical cancer, comprehensive and constant vaccination is essential for effective disease control. According to numerous studies, vaccination against HPV significantly decreases the incidence of cervical, nasopharynx, anal, vaginal, and penile cancer and also reduces the incidence of vaginal warts.
The available vaccines contain capsid protein L1 of the virus and prevent the entry of the virus into the host cells. Vaccines should be given at young ages before first exposure to the virus because they have no therapeutic benefit and have no impact on the emergence of persistent infections. Likewise, vaccination is the most efficient way to control cervical cancer, and there are currently three types of vaccines against HPV: Gardasil, Cervarix, and Gardasil 9. Gardasil, the first commercially produced vaccine, is a quadrivalent vaccine and confers protection against types 6 and 11, 16, and oncogenic types 18 of HPV. Cervarix is the bivalent vaccine and provides protection against types 16 and 18. To make vaccination more effective and prevent more cervical cancer, the nine-valent Gardasil has been produced. Gardasil 9, in addition to the types of Gardasil, contains an additional five types, including 31, 32, 52, 45, and 58, and is generally used in double doses to prevent a higher percentage of cervical cancer.
Infection with papillomaviruses is increasing, which has caused concerns in Iranian society, and it seems vital to have a widespread plan to control the infection. Preventing the spread of infection with the widespread use of vaccines at young ages and the diagnosis of infection in the primary stage is necessary to prevent the spread of infection and its transformation into cancer. Global vaccination programs have demonstrated a substantial decline in cancerous lesions associated with HPV types 16 and 18, with a reduction ranging from 90 to 100 percent. Moreover, the incidence of cervical cancer has decreased by 70 percent, and genital warts in women and men have seen reductions of 77 percent and 62 percent, respectively. Consequently, vaccination emerges as the most effective and economically feasible approach to cervical cancer prevention, particularly in developing nations. With an increasing number of cervical cancer occurrences and the undeniable connection between this cancer and HPV, there is an urgent need to set up a widespread vaccination program in Iran, where there is currently no comprehensive HPV vaccination program. This study summarizes the general knowledge and new findings of virology, pathogenicity, epidemiology, and vaccination of Human Papillomaviruses.
Type of Study: review article |
Subject:
Microbiology
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