Different Types Of Human Papillomaviruses Research Articles

Distribution of human papillomaviruses (HPV) by geographical area and affected organ in Greece

Introduction: Even today we do not have a comprehensive picture of the impact of the virus in Greece and its location at various anatomical sites. Aim: The aim of the study was to investigate and record the impact of HPV infection in the Greek population with emphasis on the affected organ/system. Methodology: The data of the tissue bank of the histology and embryology laboratory of the Medical School of Athens was utilized. It includes cases with the following characteristics: a) they are fully characterized in terms of HPV infection (complete subtyping of the virus), b) they belong to benign and malignant neoplasms of various organs with complete histopathological assessment, c) have been collected in at least the last decade d) have accompanying clinical and demographic data and e) their origin covers the entire Prefecture of Attica and a wide age range. Results: In 60% of the samples no type of HPV was detected, while in 12%, low-risk types were detected and in 28% high-risk types. Women had a higher rate of infection with different types of HPV and were at higher risk, with HPV types 16 & 18 being more common than men, who were more likely to have HPV 6 & HPV 11 types. Infection with a high-risk type occurred in 23.4% of women versus 0.3% of men. The most common type in cervical secretions was HPV 16 (14% and 10.3% respectively), followed by HPV 18 with rates of 7.4% and 10.3% respectively. Regarding skin, HPV types 16 & 18 were found with the same frequency (11.1%). In the perineum-rectum, the types of HPV6 & 11 predominated (20.7%), followed by HPV 16 & 18. Conclusion: The present study contributes to the further investigation of the prevalence of HPV in Greece, with emphasis on more types of HPV and more anatomical sites, providing information on the male population. It will help update public health planning, detect and prevent HPV-related cancers in both sexes in Greece

Papillomavirus infection and reproduction

The purpose of the review a synthesis of research data on the role of human papillomavirus infection in the reproductive health of women and men.
 Key Points. Human papillomavirus (HPV) is one of the most common sexually transmitted viruses worldwide. According to the World Health Organization, HPV is the main cause of the development of HPV-associated diseases among both women and men. Viruses are subdivided into HPV with low carcinogenic risk, which cause benign warts, and HPV with high carcinogenic risk, which cause cancer. Different types of human papillomaviruses depending on their characteristic tropism, are divided into skin and mucous types. Viral infection in men leads to a decrease in the quality of sperm (for example, asthenozoospermia) due to apoptosis in sperm cells and due to the development of antisperm immunity. A negative viral effect on the fertility of women is manifested in an increase in the frequency of spontaneous miscarriages and a premature rupture of the amniotic membranes during pregnancy. There is evidence that HPV decreases the number of trophoblastic cells and abnormal trophoblastic-endometrial adhesion is also observed. In trophoblastic cells transfected with high-risk HPV, the level of apoptosis increases. HPV vaccination is safe, and the results show not only protection against HPV-associated diseases in women and men, but also a reduction of gestational complications, reduced preterm birth rates and the protection of newborns from infection.

Characterization of genomic changes in the cervical pre-cancerous lesions and tumors induced by different types of human papillomaviruses.

Cervical carcinoma is the second most common malignancy among women in both incidence and mortality. Although much is known about the etiology and treatment of cervical cancer, the role of genetic alterations in the multistep pathway of cervical tumorigenesis is largely unknown. The aim of this study was to characterize the genomic changes in the cervical pre-cancerous lesions and tumors, induced by different types of human papillomaviruses. In this research was used the BlueGnome CytoChip oligo 2×105K microarray for whole-genome oligo-array CGH. Microarray CGH analysis of 40 specimens was carried out-12 specimens from patients with early-stage squamous cell carcinomas; 19 specimens from patients with mild to moderate dysplasia and 9 with severe dysplasia. First we performed microarray CGH analysis of five DNA pools which contained the DNA from homogeneous groups of patients. The results revealed presence of micro chromosomal aberrations in chromosome region 14q11.2. According to the genome database these aberrations represent polymorphisms. Microarray analysis of DNA from 9 separate carcinoma lesions revealed a total of 26 aberrations in 14 chromosomes of nine patients. Our results showed the advantages of high-resolution chips in the clinical diagnosis of patients with cancerous and precancerous lesions caused by viral infection with HPV, but also highlight the need for extensive population studies revealing the molecular nature and clinical significance of different CNVs and the creation of detailed maps of variations in the Bulgarian population. This would facilitate extremely precise interpretation of specific genomic imbalances in the clinical aspect.

Imiquimod in the treatment of cutaneous warts: an evidence-based review.

Cutaneous warts are highly prevalent lesions caused by the infection of keratinocytes by different types of human papillomaviruses. Although cutaneous warts are capable of resolving spontaneously, these infections can persist for long periods of time by evading the host immune system, and, as a result, many patients choose to seek treatment. Imiquimod is an immune response modifier that is approved as a topical cream for the treatment of anogenital warts by the US Food and Drug Administration. However, the efficacy of imiquimod in the treatment of cutaneous warts has not been well established. The purpose of this article is to systematically review the published literature regarding the efficacy of imiquimod in the treatment of cutaneous warts, and to evaluate the quality and outcomes of these studies. A literature search was performed through clinical queries PubMed (National Library of Medicine) database and the Cochrane database. All completed studies written in English and published through May 2014 were considered. Studies evaluating the use of imiquimod for anogenital warts were excluded. There were no other restrictions based on patient age, sex, ethnicity, or skin type. The studies were evaluated and assessed based on study design, patient population, treatment regimen, clinical outcome, and adverse events. A total of 393 records were identified in the initial search; 23 full-text articles were assessed for eligibility and included in the review. Of these studies, six publications reported on immunocompromised individuals only. The highest quality study identified was a grade B, level 3 case-control cohort study in which patients with multiple warts had certain warts treated with imiquimod and others left untreated to serve as a control. The remaining studies identified were level 4 non-controlled case series (grade C) and level 5 case reports (grade D). In immunocompetent patients enrolled in non-controlled studies, the combined rate of patients achieving complete response to therapy was 44%, ranging from 27 to 89%. However, there was variation in the dose frequency and application among these studies. In immunosuppressed patients, two studies and four case reports were identified. Clinical improvement was seen in 33-50% of patients, with no patients experiencing complete clinical clearance. There have been several studies demonstrating the successful use of imiquimod to treat recalcitrant cutaneous warts, either alone or as combination therapy. However, these studies are limited in number, include small populations, and are non-controlled. Further studies are needed to determine the efficacy of imiquimod, dose frequency and application, and optimal combination with other therapeutic measures such as paring, salicylic acid, or other destructive procedures.

Disruption of pocket protein dream complexes by E7 proteins of different types of human papillomaviruses

It has been shown that the E7 protein of the high-risk HPV-16 transforms cells in vitro and binds pRB, p107 and p130, so called pocket proteins associated in cells with DREAM proteins, while that of the low-risk HPV-6 does not transform cells and binds p130 but not pRB or p107. These facts may indicate that p130 is essential for the HPV life cycle. To gain further insight into the relationship between HPV E7 proteins and pocket protein-DREAM complexes, E7 proteins of HPVs of various risk categories were expressed via appropriate vectors in T98G cells and the levels of various pocket proteins either total or associated with DREAM were analyzed. The obtained results demonstrated that high-risk HPV-16, HPV-18 and HPV-33, low-risk HPV-1 and HPV-11, and cutaneous HPV-48 disrupted pocket protein-DREAM complexes in T98G cells to a similar extent.

Human papillomavirus typing of warts and response to cryotherapy

Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. This study demonstrates that HPV type can be determined from wart parings. HPV-2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population.

Protein Intrinsic Disorder and Human Papillomaviruses: Increased Amount of Disorder in E6 and E7 Oncoproteins from High Risk HPVs

It is recognized now that many functional proteins or their long segments are devoid of stable secondary and/or tertiary structure and exist instead as very dynamic ensembles of conformations. They are known by different names including natively unfolded, intrinsically disordered, intrinsically unstructured, rheomorphic, pliable, and different combinations thereof. Many important functions and activities have been associated with these intrinsically disordered proteins (IDPs), including molecular recognition, signaling, and regulation. It is also believed that disorder of these proteins allows function to be readily modified through phosphorylation, acetylation, ubiquitination, hydroxylation, and proteolysis. Bioinformatics analysis revealed that IDPs comprise a large fraction of different proteomes. Furthermore, it is established that the intrinsic disorder is relatively abundant among cancer-related and other disease-related proteins and IDPs play a number of key roles in oncogenesis. There are more than 100 different types of human papillomaviruses (HPVs), which are the causative agents of benign papillomas/warts, and cofactors in the development of carcinomas of the genital tract, head and neck, and epidermis. With respect to their association with cancer, HPVs are grouped into two classes, known as low (e.g., HPV-6 and HPV-11) and high-risk (e.g., HPV-16 and HPV-18) types. The entire proteome of HPV includes six nonstructural proteins [E1, E2, E4, E5, E6, and E7 (the latter two are known to function as oncoproteins in the high-risk HPVs)] and two structural proteins (L1 and L2). To understand whether intrinsic disorder plays a role in the oncogenic potential of different HPV types, we have performed a detailed bioinformatics analysis of proteomes of high-risk and low-risk HPVs with the major focus on E6 and E7 oncoproteins. The results of this analysis are consistent with the conclusion that high-risk HPVs are characterized by the increased amount of intrinsic disorder in transforming proteins E6 and E7.

Pathogenesis of human papillomaviruses in differentiating epithelia.

Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Over 100 different types of HPVs have been identified to date, and all target epithelial tissues for infection. One-third of HPV types specifically infect the genital tract, and a subset of these are the causative agents of anogenital cancers. Other HPV types that infect the genital tract induce benign hyperproliferative lesions or genital warts. The productive life cycle of HPVs is linked to epithelial differentiation. Papillomaviruses are thought to infect cells in the basal layer of stratified epithelia and establish their genomes as multicopy nuclear episomes. In these cells, viral DNA is replicated along with cellular chromosomes. Following cell division, one of the daughter cells migrates away from the basal layer and undergoes differentiation. In highly differentiated suprabasal cells, vegetative viral replication and late-gene expression are activated, resulting in the generation of progeny virions. Since virion production is restricted to differentiated cells, infected basal cells can persist for up to several decades or until the immune system clears the infection. The E6 and E7 genes encode viral oncoproteins that target Rb and p53, respectively. During the viral life cycle, these proteins facilitate stable maintenance of episomes and stimulate differentiated cells to reenter the S phase. The E1 and E2 proteins act as origin recognition factors as well as regulators of early viral transcription. The functions of the E5 and E1--E4 proteins are still largely unknown, but these proteins have been implicated in modulating late viral functions. The L1 and L2 proteins form icosahedral capsids for progeny virion generation. The characterization of the cellular targets of these viral proteins and the mechanisms regulating the differentiation-dependent viral life cycle remain active areas for the study of these important human pathogens.

Human papillomaviruses and their role in cervical cancer.

Human papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably cancer of the cervix, a disease responsible for at least 200,000 deaths per year worldwide. Over 100 different types of HPV have been identified and these can be divided into two groups. Low-risk HPV types are the causative agent of benign warts. High-risk HPV types are associated with cancer. This review focuses on the role of high-risk HPV types in cervical tumorigenesis. Recent work has uncovered new cellular partners for many of the HPV early proteins and thrown light on many of the pathways and processes in which these viral proteins intervene. At the same time, structural and biochemical studies are revealing the molecular details of viral protein function. Several of these new avenues of research have the potential to lead to new approaches to the treatment and prevention of cervical cancer.

Searching for Antiviral Drugs for Human Papillomaviruses

The human papillomaviruses (HPVs) are ubiquitous human pathogens that cause a wide variety of benign and pre-malignant epithelial tumours. Of the almost 100 different types of HPV that have been characterized to date, approximately two dozen specifically infect genital and oral mucosa. Mucosal HPVs are most frequently sexually transmitted and, with an incidence roughly twice that of herpes simplex virus infection, are considered one of the most common sexually transmitted diseases throughout the world. A subset of genital HPVs, termed 'high-risk' HPVs, is highly associated with the development of genital cancers including cervical carcinoma. The absence of a simple monolayer cell culture system for analysis and propagation of the virus has substantially retarded progress in the development of diagnostic and therapeutic strategies for HPV infection. In spite of these difficulties, great progress has been made in the elucidation of the molecular controls of virus gene expression, replication and pathogenesis. With this knowledge and some important new tools, there is great potential for the development of improved diagnostic and prognostic tests, prophylactic and therapeutic vaccines, and traditional antiviral medicines.

Papilloma virus: tools and vectors

Human papillomaviruses (HPVs) are a group of small DNA viruses associated with benign and malignant epithelial cancers of cutaneous or mucosal origin. More than 75 different types of HPV have been isolated, each type exhibiting a particular tropism for certain kinds of epithelia. Particular types of HPVs (HPV16, 18 and a few rarer types—31, 33 and 45) are suspected to be the causative agents of at least 95% of cervical cancers, the second-most frequent cancer in women worldwide. The medical importance of these pathogens has driven intensive research efforts: the genetic organization of their genomes is now solved and the functions of their genes are essentially understood. However, other areas of the HPV life cycle are not so well characterized, such as how HPV DNA is packed and unpacked, and how the virions dock onto target cells.

Two different human papillomavirus (HPV) types associated with oral mucosal lesions in an HIV‐seropositive man

Different types of Human papillomaviruses (HPV) are associated with a variety of oral lesions. So far, HPV types 1, 2, 4, 6, 7, 11, 13, 16, 18, 32 and 57 have been identified in oral lesions. Immunosuppression predisposes oral mucosa to clinical manifestation of different virus infections including HPV. We describe here a 30-year-old HIV-positive and immunosuppressed man, who had suffered from oral lesions for a few months. On clinical examination, a nodular elevation was detected on the lower lip, and white keratotic areas were present on buccal mucosa bilaterally. A biopsy from the lip revealed the presence of acanthosis with a prominent granular cell layer as well as hyperparakeratosis. A biopsy from the buccal lesion showed a comparatively much flatter lesion with merely basal cell hyperplasia associated with hyperparakeratosis. Koilocytosis was a characteristic feature in both biopsies. In Southern blot hybridization, both lesions hybridized with a probe cocktail comprising HPV 6, 11, 16, 18, 31 and 33 DNA under low stringency. Under high stringency, the lip lesion proved to contain HPV 7 DNA, which also confirmed by in situ hybridization. The buccal lesion was weakly positive by Southern blot with HPV 11 and 13 probes hybridized under stringent conditions, but the restriction patterns with Pst I and Bam HI did not fit with those of any of the 57 HPV types known so far. In situ hybridizations with HPV 11 and HPV 13 probes were negative. Cloning of this 'new' HPV type is currently under way.