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, barzegar.soheyla@yahoo.com
Abstract:   (311 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, small nonenveloped viruses that have double-strand DNA genome. Since HPV cannot grow in tissue cultures, molecular hybridization assays are used for detection and classified into more than 200 types based on DNA sequences. In most cases, infections with this virus are asymptomatic and benign which can be eliminated by the host immune system during 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 and High-Risk 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 genotypes16 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, virus needs to access the basal layer of the skin tissue lamina propria. 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 and is the key factor for 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 progress 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 malignancy.
HPV can evade the host immune system through expression of its own proteins at the lower layer of epithelium.  Also, 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 the one of most common sexually transmitted infections and 2 to 44 percent of women are infected with this virus. Cervical cancer is the fourth most prevalent cancer among women with a high mortality rate especially in developing countries and HPV is responsible for approximately 90 percent of cases worldwide. In Iran, the infection rate varies from 7 to 24 percent, and in 78.8 to 79.3 percent of cervical cancer cases, HPV infection is detectable. Due to the lack of specific treatment against the virus and the direct connection between persistent infection of HPV and cervical cancers, the comprehensive and constant vaccination is essential to 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 it has no therapeutic benefit and has 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 vaccine against HPV: Gardasil, Cervarix, and Cervarix 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 9 has been produced. Gardasil 9 in addition to the types of Gardasil, contains additional five types including 31, 32, 52, 45, and 58, and generally is used in double dose to prevent more percent of cervical cancer.
Likewise, 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 diagnosis of infection in the primary stage is necessary to prevent the spread of infection and its transformation into cancer. The vaccination programs worldwide have indicated that the incidence of cancerous lesions caused by HPV types 16 and 18 is reduced by 90–100 percent, cervical cancer by 70 percent, and genital warts are lowered in women by 77 and in men by 62 percent, so vaccination is the best and most affordable way to prevent cervical cancer in developing countries. With an increasing number of cervical cancer occurrences and the undeniable connection between this cancer and HPV, it seems urgent 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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