Specific Aims
Human papillomavirus (HPV) infections cause cervical cancers, and some cancers of the vulva, vagina, penis, anus, and oropharynx. Two prophylactic HPV vaccines (Gardasil® and Cervarix®) can block new infections from a subset of the most prevalent HPV types, but have shown no therapeutic effect against pre-existing diseases. No effective therapeutics exists at present, and the mechanisms of HPV-associated disease progression and cancer are not well understood.
Persistent HPV infection is the greatest risk factor for the development of malignancies. How the host defense system achieves control of viral infection remains incomplete, partially due to the lack of adequate small animal models. Our long-term goal is to understand the role of innate immunity that leads to the clearance of HPV/PV infections. The specific objective of this revised proposal is to use the newly established mouse papillomavirus (MmuPV1) model to test the central hypothesis that innate immunity plays a role in papillomavirus-induced infections. We have developed the MmuPV1 infection model with a broad tropism as well as a panel of viral and immunological reagents to aid our long-term studies. The rationale for these studies is that the MmuPV1/mouse model is an
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We hypothesize that type I IFN pathway plays a role in MmuPV1-associated infection and tumor growth. Type I IFN not only plays an essential role in defense against papillomavirus infection at any stage of the virus life cycle but also regulates multiple aspects of innate and adaptive immunity. We propose to test gene knockout mice including type I (Ifnκ-/- and IFN-αβR-) and type I plus type II (Stat1-/-) to evaluate the role of IFNs and/or their receptors in papillomavirus-associated diseases. These gene knockout mice will help us to elucidate the role of type I IFN pathways in papillomavirus-associated infection and
Human papillomaviruses (HPV) are a group of more than 40 types of viruses that infect the genital areas, throats (recurrent respiratory papillomatosis), and mouths of males and females and is the number one most common sexually transmitted disease (Center for Disease Control and Prevention [CDC], 2009). It is spread by genital contact. It is most easily spread by vaginal and anal sex, but also through oral sex and even just genital-to-genital (skin-to-skin). In 90% of people that contract HPV, their own immune system
Our laboratory has developed the mucosal MmuPV1 infection mouse model recently and noninvasive methods to track the infection from oral and anogenital canals longitudinally [14]. Our long term goal is to use this model to explore many unanswered questions regarding viral-host interaction during papillomavirus infection. Innate immunity, a critical part of host defense system, is not only the first line of defense against pathogens, but is also critical for stimulating adaptive immune responses in viral infection [15-22]. Other host defense factors including interferons, Toll-like receptors, cytokines and defensins all play an important role in papillomavirus persistence and progression [23-31]. However, some findings in human studies are inconsistent
Human papillomavirus (HPV) is made up of double stranded DNA with a capsid. Their viral genome is consisting of such as early (E) gene like E6 and E7encodes for oncoproteins and late (L) gene such as L1 and L2 encodes for structural proteins like capids. There are more than 100 different types of HPV identified and they generally infect around cutaneous or mucosal areas. HPV viral genome can be categorized into low risk (LR) and high risk (HR). High risk types such as HPV-16 and -18 are ones that can develop into cancer and other tumors mostly in genital area or a head and neck squamous cell. Low risk types such as HPV-6 and -11 are more frequently found I larynx or genital area (Klozar et al., 2010). Therefore, careful evaluation such as risk factors, or possibly a new vaccination to prevent against HPV related to oropharyngeal SCC should be questioned in public health
Almost all cervical carcinomas are caused by Human papillomavirus (HPV). Cervical cancer can be a life-threating disease. However, over recent years the occurrence of cervical cancer has declined as well as the chance of dying from it. A huge contributing factor to this decline is the importance of a regular pap smear. A pap smear can find cervical pre-cancer before it turns into cancer. Recently, a vaccine for HPV, has been on the market, which provides close to a 100% protection against pre-cancer and general warts. HPV and cervical cancer are two disease that are closely related. However, each disease effects not only similar populations, but also different populations, as well as having its own signs and symptoms, detection procedures,
The HPV virus has gone unseen by many until the recent controversy over the vaccine. However, this virus is thought to be one of the world’s most wide spread STD’s. “According to the Centers for Disease Control and Prevention (CDC), about 6.2 million women and men are newly infected every year” with HPV. HPV has over 100 strains, with more than thirty that are sexually transmitted. Some of these strains are known to cause cervix, vulva, vagina, anus, or penis cancers and others can cause genital warts. “Studies have found the vaccine to be almost 100% effective in preventing diseases caused by the four HPV types covered by the vaccine—including precancers of the cervix, vulva and vagina, and genital warts” (“HPV Questions and
Human Papilloma Virus (HPV) is the causative operator of cervical disease, which is a standout amongst the most unmistakable tumors in ladies. HPV is a sexually transmitted malady that can influence both men and ladies. The immunizer discovery systems uncovered that the greater part of the ladies (those that are sexually dynamic) worldwide and roughly 70% of the sexually dynamic ladies of US populace have been presented to the papilloma infection sooner or later in time. The African area is having the most astounding rate of commonness with an expected number of 379153 cases amid the year 2000.
Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections in the United States. HPV belong to a family of viruses that cause cell changes in the epithelia resulting in benign skin lesions called warts and verrucae. Type 6 and 11 cause warts and are included under the low risk HPVs,Types 16,18,31,33,45 cause cervical cancer and are included under high risk HPVs(CDC,2014). The virus affects the skin and mucous membrane especially of the reproductive organs. Cervical Cancer and other Ano-genital cancers are seen in women with persistent genital HPV infection. HPV that affects the
Human Papilloma Virus (HPV) accounts for the third most prevalent cancer in females worldwide,15 as it is the most common sexually transmitted infection (STI).2 There are more than 100 subtypes of HPV; 16 of those subtypes are known to be high-risk.15 HPV is a crucial precursor to cervical cancer in 99.8% of those affected,2 with subtypes 16 and 18 being the most common types.15
According to the National Cancer Institute, not all human papillomaviruses (HPV) cause cancer. There are two types of categories; the low risk and high risk human papillomaviruses. If one contracts a high risk HPVs, they have a chance of developing cancer. High risk HPVs can lead to cervical cancer, anal cancer, oropharyngeal cancer, vaginal cancers, vulvar cancers, and penile cancers (1). The National Cancer Institute states that HPVs account for causing 5% of cancers and Nathan Seppa proclaims “that the two cancer-causing virus subtypes... HPV-16 and HPV-18, account for more than half of cervical cancers” (1 and 2). This demonstrates the overall impact HPV has on causing cancer.
In the United States, cervical cancer is known as one of the most common cancers amongst females and it is estimated that 1/3 of the females diagnosed will die (Parkin, Bray, Ferlay, & Pisani, 2005). HPV 16 is the most common detected virus in cervical cancer patients, but there are 14 HPV types that are considered high-risk (Parkin, Bray, Ferlay, & Pisani, 2005). HPV is related to cervical cancer as the virus changes the cells of the cervix and causes cervical dysplasia, which untreated, leads to cancer (Dizon & Krychman, 2010). Examining the problem from a global perspective, Biological Study on Cervical Cancer (IBSCC) study group, concluded that “HPV DNA was detected in 93% of the tumors and … HPV 16 was present in 50% of the specimens…” (Bosch, Manos, Muñoz, Sherman, Jansen, Peto & Shan, 1995). This group collected samples of 1000 patients whom were diagnosed with stage 3 cervical cancer from 32 hospitals in 22 countries (Bosch, Manos, Muñoz, Sherman, Jansen, Peto & Shan, 1995). As, represented earlier with current statistics, it’s evident that more people are diagnosed each year with cervical cancer that have HPV present
Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections in the United States. HPV belong to a family of viruses that cause cell changes in the epithelia resulting in benign skin lesions called warts and verrucae. Type 6 and 11 cause warts and are included under the low risk HPVs,Types 16,18,31,33,45 cause cervical cancer and are included under high risk HPVs(CDC,2014). The virus affects the skin and mucous membrane especially of the reproductive organs. Cervical Cancer and other Ano-genital cancers are seen in women with persistent genital HPV infection. HPV that affects the skin can be transmitted by skin to skin contact with an affected person and Genital HPV is spread through Kissing and Oral
Human Papilloma Virus (HPV) is a communicable, sexually transmitted disease with high prevalence rates in the general population (CDC, HPV, 2015). Although many people who contract this disease will never develop clinical symptoms, HPV may cause cancer many years later (CDC HPV, 2015). For example, one in every 142 women will develop cervical cancer due to HPV in her lifetime (CDC HPV, 2015). HPV vaccines have been developed and administered in recent years for the prevention of HPV and cervical cancer, but it must be given prior to HPV exposure (CDC HPV, 2015). The HPV vaccine is greater than 90% effective in eradication of the HPV strains that cause cancer (CDC, HPV, 2015). HPV has unique public health implications since it is rare that vaccines can prevent future cancers.
Human papillomavirus, commonly abbreviated as HPV, is the most common sexually transmitted virus that can cause a variety of diseases. It is transferred from person to person by either genital contact or from oral contact. Most men and women who are sexually active will be infected with this virus at least once in their life (“HPV”). A reason why HPV has become such a big problem in society is because of the fact that it is a virus, and thus cannot be treated with antibiotics. For other viral infections, it is possible to wait for the body’s immune system to rid the body of the foreign invader, but HPV is a virus that can cause more serious health problems such as genital warts, cancers of the mouth, anus, or vagina, as well as the cervix. Another reason why this problem exists in society may be due to more relaxed standards regarding sexual activity. In today’s society, people are more likely to have more than one sexual partner, making it easier for the virus to spread within the population. People are also becoming sexually active at younger ages before they receive education about safe sex at school or at home, which is also a factor in the spread of HPV in the population. Most people do not exhibit negative symptoms from the virus; indeed, some of them may not even know they have contracted it, for the body can clear out the virus on its own ninety percent of the time (“What is HPV?” 2013). HPV
In this study, we have expanded the spectrum of HPV+ HNSCC-specific immune therapeutic targets at the CTL-epitope level and at the target tumor cell-modulatory level. We chose E2, E6 and E7-antigens, as they induce strong B-cell immunity, have been detected in pre-invasive and/or invasive cervical cancer, and we confirmed viral antigen expression in HPV16+ HNSCC transcriptomes. Most studies that have attempted to define CTL-immunogenicity from HPV16 have primarily focused on a limited number of HLA-alleles (e.g. A*02:01) and peptides from E6 and E7 (Table B1), with limited data on immunogenic targets in in HPV+ HNSCC (Ressing et al., 1995; Riemer et al., 2010; Rudolf, Man, Melief, Sette, & Kast, 2001). The 15 HLA alleles chosen for this
Wounding has been reported necessary for a HPV pseudovirus to deliver marker gene in mouse vaginal tract (Roberts et al., 2007). For skin infection, we found that pre-wounding did improve the viral infectivity in our rabbit papillomavirus model (Cladel et al., 2008). We compared vaginal infection with and without wounding in our MmuPV1 model. Although we found that wounding promoted infection at an earlier time, but it is not essential for MmuPV1 infection at the genital tract. One reason is the nature of low amount of target DNA encapsidating inside pseudovirus (Holmgren et al., 2005). Our unpublished study demonstrated that natural virions contain most viral DNA. Therefore, the efficiency of naturally viral infection is much higher when compared with the