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Immunobiology of HPV Infection
Archives of medical research, 2009
Although the high-risk human papillomavirus (HPV) is necessary to cause cervical cancer (CC) and its infectious origin is well recognized, neither the systemic nor the local immune responses to this virus has been well studied or understood. Because the many facets of HPV are excellently described here by others, we will focus on the immune responses of the female genital tract, especially in situ, or in natura, as Casanova argues when studying diseases (1). A general overview is provided where different elements of the innate and adaptive immunity are discussed. We highlight the very successful strategy used by HPV with a protracted and seemingly silent infection, making this virus extremely well adapted to infect humans. The counterpart of this peculiar immunological situation is that whatever immune responses (innate or adaptive, local or systemic) are induced in those chronically infected women, these responses are inefficient to cope with and especially to eradicate the virus, thus resulting in viral persistence. A further follow-up of this line of thought is that among other well-known co-factors some still uncovered complex immune alterations may underlie the enigmatic susceptibility of the minority of women permissive to the chronic HPV infection, i.e., of those who slowly progress from infection to CIN 1e2e3 and then to invasive cervical carcinoma.
Cellular immunity against human papillomavirus associated cervical cancer
Seminars in Virology, 1996
Human papillomaviruses contain a double stranded circular DNA genome of about 8 kilobases in size. More than 95 genotypes have been described of which several types are associated with cancer, like cervical carcinoma. The HPV types associated with cervical carcinoma (high risk types) are predominantly HPV16 and 18 and less frequently HPV31, 33, 35 and 45. 3, HPV DNA is detected in nearly 100% of cervical carcinomas and 60% of these are accounted for by HPV16. 4, Development of cervical cancer is preceded by cervical dysplasia, classified as cervical intraepithelial neoplasia (CIN) grade I-III based on histological criteria. The prevalence of HPV increases from about 60% in CIN I to almost 100% in CIN III. In cervical smears of symptom-free women, the prevalence of HPV is dependent on age and varies from 15 to 20% (15-30 years of age) and from 5 to 10% (over 30 years of age). 4,9 The high risk HPV are transmitted via sexual intercourse 10,11 after which they infect the basal layers of the epithelium of the anogenital tract in which they replicate. 12,13 Since these replication conditions cannot yet be mimicked in vitro, immunologic research on HPV has been hampered by the lack of obtaining sufficient amounts of intact HPV16 virions. The early region 6 and 7 (E6 and E7)-encoded oncoproteins of the high risk HPV genotypes were shown to bind the tumor suppressor gene products p53 and pRb, respectively. As a result the cell cycle control mechanisms in which p53 and pRb play a key role are deregulated. 14,15 These findings indicate a direct involvement of the E6 and E7 proteins in oncogenesis. Since E6 and E7 are the only HPV proteins constitutively expressed in cervical cancer cells 16,17 and maintenance of the transformed phenotype of cells transfected with HPV16 depends on intact E6 and E7 expression, 19,20 the E6 and E7 oncoproteins seem suitable targets for T-cell mediated immunotherapy of cervical cancer.
Clinician's guide to human papillomavirus immunology: knowns and unknowns
The Lancet Infectious Diseases, 2009
Oncogenic human papillomavirus (HPV) is a common genital infection that has the potential to develop into cervical cancer in some women. This Review summarises current knowledge on the mechanisms of host immunity that help prevent and control HPV infection and the viral factors that exist to avoid immune surveillance. Although most women clear the infection within a few months, the virus induces a shift towards immune tolerance that can facilitate persistence and permit tumorigenesis. Mechanisms used by HPV to avoid immune surveillance and control include infecting only the basal layer of the cervical epithelium, limiting expression of viral proteins until later stages of epithelial diff erentiation, undergoing non-lytic replication, and downregulating the expression of important receptors on cells of the innate immune system.
Published by Wolters Kluwer - Medknow, 2025
The most common STD that triggers cervical cancer is the human papillomavirus. More than 20 types of human papillomavirus (HPV) can induce uterine cervical cancer. Almost all women acquire genital HPV infection soon after their first intercourse, with most of them clearing the virus within 3 years. An immune response is necessary to clear. The f irst responders to HPV infection are the innate immune system elements composed of macrophages, keratinocytes, natural killer cells, and natural killer T-lymphocytic (NKT) cells. Cytotoxic T lymphocytes (CTLs) comprise the second line of defense and kill HPV16-infected cells expressing various peptides derived from their transforming early viral oncoproteins, mainly E2•E6. Even though HPV can manage to trick away our immune systems, first of all, it is important to emphasize that HPV replication does not kill the host cells. It does not replicate viral antigens or cause inflammation. The HPV16 E6 and E7 genes suppress host cell type 1 interferons (IFNs), which are detectable after infection. The patient may have immunological tolerance; hence, there are no costimulatory signals from inflammatory cytokines like IFNs during antigen recognition. Evidence shows that HlA class I generations have been inhibited by HPV16 E5, which could protect this tumor cell from CTL attack. HPV16 E7 is responsible for initiating immunotolerance and increasing regulatory T cells (Treg) to repress immunological regression. Evasion from immune system protection plays a critical role in the outcome of persistent HPV infection and the development of cervical cancer. Vaccination against HPV16 and 18 during adolescence is the most effective method for preventing cervical cancer in women, considering the immunological processes involved. Keywords: Acquired immunity, Human papillomavirus, Immune escape, Natural immunity, Uterine cervical cancer
Open Access Journal of Clinical Trials Biology and natural history of human papillomavirus infection
Human papillomavirus (HPV) is one of the most common causes of sexually transmitted diseases worldwide. It has been proposed that the great majority of women and men have been infected with HPV at least once during their lifetime. HPV infection is associated with a variety of clinical conditions, ranging from benign lesions to cervical cancer. In most cases, the infection is transient, where most of the individuals are healing, eliminating the virus without the presence of any clinical manifestation. Actually, more than 120 HPV types have been cataloged, of which approximately 40 can infect the mucosa of the anogenital tract and are collectively known as mucosal HPV, which are classified based on their oncogenic potential as either low-or high-risk HPV types. The low-risk HPV type causes benign hyperproliferative lesions or genital warts, with a very limited tendency for malignant progression, while the high-risk HPV type is strongly associated with premalignant and malignant cervical lesions. The HPV cycle initiates when the virus gains access to undifferentiated cells of the basement membrane of the squamous columnar junction epithelium of the ectocervix, after these regions are exposed to mechanical or chemical trauma. The basal cells in the transformation zone retain the ability to differentiate, a property required for virion production. Cervical infection with high-risk HPV typically lasts from 12 to 18 months and in most cases is cleared spontaneously. However, in some women the immune response is insufficient to eliminate the virus, resulting in a persistent, long-term infection that may progress to a malignant lesion. In this review, we discuss the biology and natural history of HPV infection and its association with cervical cancer.
Chapter 1: HPV in the etiology of human cancer
Vaccine, 2006
The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of the vagina and anus are likewise caused by HPV, as are a fraction of cancers of the vulva, penis, and oropharynx. HPV-16 and -18 account for about 70% of cancers of the cervix, vagina, and anus and for about 30-40% of cancers of the vulva, penis, and oropharynx. Other cancers causally linked to HPV are non-melanoma skin cancer and cancer of the conjunctiva.
Microorganisms
Human papillomavirus (HPV) infection is associated with precancerous lesions and cancer of the genital tract both in women and men. The high incidence of cervical cancer worldwide focused the research on this infection mainly in women and to a lesser extent in men. In this review, we summarized epidemiological, immunological, and diagnostic data associated with HPV and cancer in men. We presented an overview of the main characteristics of HPV and infection in men that are associated with different types of cancer but also associated with male infertility. Men are considered important vectors of HPV transmission to women; therefore, identifying the sexual and social behavioral risk factors associated with HPV infection in men is critical to understand the etiology of the disease. It is also essential to describe how the immune response develops in men during HPV infection or when vaccinated, since this knowledge could help to control the viral transmission to women, decreasing the in...
HPV Infection: Immunological Aspects and Their Utility in Future Therapy
Infectious Diseases in Obstetrics and Gynecology, 2013
High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (T...