scholarly journals The Human Papillomavirus Type 16 E7 Oncoprotein Activates the Fanconi Anemia (FA) Pathway and Causes Accelerated Chromosomal Instability in FA Cells

2007 ◽  
Vol 81 (23) ◽  
pp. 13265-13270 ◽  
Author(s):  
Nicole Spardy ◽  
Anette Duensing ◽  
Domonique Charles ◽  
Nathan Haines ◽  
Tomomi Nakahara ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Squamous Cell ◽  
Fanconi Anemia ◽  
Chromosomal Instability ◽  
Hpv Infection ◽  
Hpv 16 ◽  
E7 Oncoprotein ◽  
Increased Risk ◽  
Frequent Event

ABSTRACT Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection for infection with high-risk human papillomavirus (HPV) types, including the oral cavity and the anogenital tract. We show here that activation of the FA pathway is a frequent event in cervical SCCs. We found that FA pathway activation is triggered mainly by the HPV type 16 (HPV-16) E7 oncoprotein and is associated with an enhanced formation of large FANCD2 foci and recruitment of FANCD2 as well as FANCD1/BRCA2 to chromatin. Episomal expression of HPV-16 oncoproteins was sufficient to activate the FA pathway. Importantly, the expression of HPV-16 E7 in FA-deficient cells led to accelerated chromosomal instability. Taken together, our findings establish the FA pathway as an early host cell response to high-risk HPV infection and may help to explain the greatly enhanced susceptibility of FA patients to squamous cell carcinogenesis at anatomic sites that are frequently infected by high-risk HPVs.

scholarly journals Oral human papillomavirus infection in HIV-infected and HIV-uninfected MSM: the OHMAR prospective cohort study

2020 ◽  
Vol 96 (7) ◽  
pp. 528-536 ◽  
Author(s):  
Massimo Giuliani ◽  
Francesca Rollo ◽  
Maria Fenicia Vescio ◽  
Barbara Pichi ◽  
Alessandra Latini ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Incidence Rates ◽  
Oral Sex ◽  
Sex Partners ◽  
Oral Rinse ◽  
Increased Risk ◽  
Frequent Event ◽  
Oral Hpv

ObjectiveWe aimed to assess incidence and clearance of oral human papillomavirus (HPV) infection and the respective risk factors in HIV-infected and uninfected men who have sex with men (MSM).MethodsOral rinse and gargles were collected semiannually from 244 MSM (103, 42.2% HIV-infected). HPV-DNA testing was performed with the Linear Array HPV Genotyping test. A Markov model was used for estimation of incidence, clearance and risk factor analysis.ResultsIncidence rates for any HPV were 21.2 and 15.0×1000 person-months in HIV-infected and uninfected MSM, respectively. The respective figures for high-risk HPVs were 10.7 and 6.5×1000 person-months. The clearance rate was 4–12 times higher than the respective incidence rate. HIV-infected MSM with >95 lifetime oral sex partners showed increased incidence of any HPV (adjusted HR, aHR: 8.46, 95% CI 1.89 to 37.92). Condomless oral sex appeared the strongest predictor for incident infection by high-risk HPVs in this group (aHR: 13.40, 95% CI 2.55 to 70.53). Those aged >46 years (aHR: 0.30, 95% CI 0.12 to 0.74) and those with nadir CD4+ T count of <200 cells/mm3 (aHR: 0.14, 95% CI 0.03 to 0.75) displayed a significantly reduced clearance of any and high-risk HPVs, respectively. HIV-uninfected MSM aged >46 years had increased risk of acquiring any HPV (aHR: 3.70, 95% CI 1.30 to 10.52) and high-risk HPV (aHR: 5.33, 95% CI 1.06 to 26.68). Any HPV clearance declined in those with more than six recent oral sex partners (aHR: 0.18, 95% CI 0.05 to 0.65).ConclusionsAcquisition of oral HPV infection in MSM seems to occur rarely, whereas clearance seems to be a frequent event. Oral HPV natural history in these at-risk subjects is differently influenced by age and sex behaviour, depending on HIV status.

Prevalence and Genotype distribution of Human Papillomavirus Infection in Different Anatomical Sites among Men Who Have Sex with Men (MSM): A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Mohammad Farahmand ◽  
Seyed Hamidreza Monavari ◽  
Ahmad Tavakoli
Keyword(s):  
Systematic Review ◽  
Human Papillomavirus ◽  
High Risk ◽  
Sexual Behaviors ◽  
Meta Analysis ◽  
Hpv Infection ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Pertinent Data ◽  
Sex With Men

Abstract Background: Homosexual men or men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviors. In this large study, a meta-analytic approach was used to systematically analyze the literature to elucidate the prevalence and genotype distribution of anal, penile, oral, and urethral HPV infection among MSM in the world.Methods: To carry out this systematic review, five electronic databases were searched for relevant studies published from January 2012 through to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalences were calculated for each anatomical region using random-effect model weighted by the inverse variance method. Subgroup analyses were performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the “Metaprop” function in the R package Meta.Results: The overall pooled prevalence of anal, penile, oral, and urethral HPV infection among MSM were 78.11 % (95% CI: 75.50%-80.52%), 36.26% (95% CI: 29.13%–44.05%), 17.33% (95% CI: 13.65%–21.75%), and 15.40% (95% CI: 7.86%–27.97%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis, and oral cavity was HPV-16 (20.32%, 4.96%, and 3.16%, respectively). Conclusion: HPV infection is on the dramatic rise in MSM because of high-risk sexual behaviors, strongly suggesting the increased risk of developing HPV-related diseases and malignancies in this population. Among different sexual orientations, male homosexuality is associated with the highest risk of acquiring sexually transmitted infections.

scholarly journals The Relationship between Cocaine Use and Human Papillomavirus Infections in HIV-Seropositive and HIV-Seronegative Women

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Howard Minkoff ◽  
Ye Zhong ◽  
Howard D. Strickler ◽  
D. Heather Watts ◽  
Joel M. Palefsky ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Pap Smear ◽  
Crack Cocaine ◽  
Hpv Infection ◽  
Cocaine Use ◽  
Hpv Dna ◽  
Increased Risk ◽  
Hiv Seropositive ◽  
Oncogenic Hpv

Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV.Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types.Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97).Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

scholarly journals Prevalence of Human Papillomavirus Associated with Head and Neck Squamous Cell Carcinoma in Jordanian Patients

2020 ◽  
Vol 14 (1) ◽  
pp. 57-64
Author(s):  
Ashraf I. Khasawneh ◽  
Nisreen Himsawi ◽  
Jumana Abu-Raideh ◽  
Muna Salameh ◽  
Niveen Abdullah ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Prophylactic Measures

Background: In addition to smoking and alcohol consumption, human papillomavirus (HPV) is a leading etiology for Head and Neck Squamous Cell Carcinoma (HNSCC). However, this causal association is still understudied in Middle Eastern populations. Objective: The aim of this study was to determine the prevalence of HPV-associated infection in the Jordanian HNSCC patients and the associated HPV genotypes. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) squamous cell carcinoma samples of the head and neck were collected from two referral centers in Amman, Jordan to determine the existence of HPV DNA. After DNA extraction HPV infection and genotyping were identified using real-time PCR. Results: HPV DNA was detected in 19 out of 61 (31.1%) HNSCC samples. Despite screening for 28 different genotypes, HPV 16 was the only genotype identified in all examined samples. Most HPV-positive samples were obtained from the oropharynx (41.7%), oral cavity (37%), and larynx (18.2%). No significant association between HPV 16 genotype and age, sex, tobacco use, anatomical location, or tumor grade was noticed. Conclusion: This study reported a high association between HPV 16 genotype and HNSCC in Jordanian patients. These data should facilitate the implementation of appropriate HPV awareness campaigns, and activate selective prophylactic measures against HPV infection.

scholarly journals Human Papillomavirus Type Distribution and Correlation with Cyto-Histological Patterns in Women from the South of Italy

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Menegazzi ◽  
Luisa Barzon ◽  
Giorgio Palù ◽  
Elisa Reho ◽  
Luigi Tagliaferro
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Multiple Infection ◽  
Multiple Infections ◽  
The South ◽  
Hpv 16 ◽  
Specific Distribution ◽  
Hpv Types ◽  
High Risk Hpv

Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage.

scholarly journals Clinical Implications of Human Papillomavirus in Head and Neck Cancers

2006 ◽  
Vol 24 (17) ◽  
pp. 2606-2611 ◽  
Author(s):  
Carole Fakhry ◽  
Maura L. Gillison
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Head And Neck ◽  
Sexual Behaviors ◽  
Hpv Infection ◽  
Genetic Alterations ◽  
Sufficient Evidence ◽  
Clinical Implications ◽  
Risk Of Death ◽  
Increased Risk

Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.

scholarly journals Identification of High-Risk Human Papillomavirus DNA, p16 and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1008
Author(s):  
Andrejs Lifsics ◽  
Valerija Groma ◽  
Maksims Cistjakovs ◽  
Sandra Skuja ◽  
Renars Deksnis ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Squamous Cell ◽  
Surrogate Marker ◽  
Hpv Infection ◽  
Hpv16 E6 ◽  
Hpv Dna ◽  
Molecular Virology ◽  
Hpv E6 ◽  
E6 And E7

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.

scholarly journals Human Papillomavirus Prevalence in Urine Samples of Asymptomatic Male Sexual Partners of Women with Sexually Transmitted Diseases

2021 ◽  
Vol 18 (21) ◽  
pp. 11706
Author(s):  
Hyunwoo Jin ◽  
Dong Hyeok Kim ◽  
Kyung Eun Lee
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Sexually Transmitted Diseases ◽  
Rapid Test ◽  
Hpv Infection ◽  
Sexual Partners ◽  
Urine Samples ◽  
Hpv 16 ◽  
Sexually Transmitted ◽  
Male Sexual Partners

Human papillomavirus (HPV) infection in males is associated with various cancers, including cervical cancer in women and penile and bladder cancers in men. However, there is limited research on the prevalence and prevention of male HPV infection. Moreover, a rapid test that can prevent the increase in HPV infection is needed. In this study, the prevalence of sexually transmitted pathogen (STP) and HPV infection was analyzed using real-time polymerase chain reaction assay in random urine samples collected from asymptomatic male sexual partners of women with sexually transmitted diseases. Among 130 men, 65 (50.0%) had STP and 12 (9.23%) had HPV infection. There was no association between STP and HPV infection. Among 12 cases of HPV infection, three were HPV-16 single infections, six were multiple infections, including HPV-16, and three of other high-risk HPV infections. Our results suggest the need for STP testing, including HPV testing, in sexual partners of high-risk women with sexually transmitted diseases, even in men without clinical symptoms (asymptomatic). Further research should be conducted by diversifying urine samples. We report the most convenient method for HPV detection, and it is expected to be widely applied to prevent sexually transmitted diseases in men and women.

scholarly journals Detection Rates of Human Papillomavirus Associated with Cervical Cancer in Women of Nizhny Novgorod

2020 ◽  
pp. 44-47
Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Detection Rates ◽  
High Risk Hpv ◽  
Incident Cases ◽  
Oncogenic Hpv

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.

scholarly journals Cross-Reactivity, Epitope Spreading, andDe NovoImmune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines

2015 ◽  
Vol 22 (7) ◽  
pp. 679-687 ◽  
Author(s):  
Mayumi Nakagawa ◽  
William Greenfield ◽  
Andrea Moerman-Herzog ◽  
Hannah N. Coleman
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Cross Reactivity ◽  
Cross Protection ◽  
Epitope Spreading ◽  
Therapeutic Vaccines ◽  
Hpv 16 ◽  
Hpv Types ◽  
High Risk Hpv

ABSTRACTNumerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, andde novoimmune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed.

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