MicroRNAs are biomarkers of oncogenic human papillomavirus infections.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC3964092 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Papillomaviruses are one of the oldest viruses known, dating back 330 million years. During this long evolution, human papillomaviruses (HPV) have developed into hijackers of human cellular and immune systems in which they replicate and remain silent. Systematic studies on oral HPV infections and their outcomes are still scarce. Oral HPV infections have been linked to sexual behaviour, but recent evidence supports their horizontal, mouth-to-mouth, transmission. Most HPV infections in infants are acquired vertically from the mother during the intrauterine period, during delivery, or later via saliva. The best-known benign clinical manifestations of HPV infection are oral papilloma/condyloma and focal epithelial hyperplasia. Evidence is emerging which suggests that some oral HPV infections might persist. Persistent HPV infection is mandatory for HPV-associated malignant transformation. However, progression of HPV-induced lesions to malignancy requires additional cofactors. In the early 1980s, we provided the first evidence that a subset of oral cancers and other head and neck cancers might be causally linked to HPV infection. This review summarizes current knowledge on the virus itself, its transmission modes, as well as the full spectrum of oral HPV infections - from asymptomatic infections to benign, potentially malignant oral lesions, and squamous cell carcinoma.
| S-EPMC6174935 | biostudies-literature
Project description:Most infections by human papillomaviruses (HPVs) are `acute', that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remains essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high, worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence.
| S-EPMC5691644 | biostudies-literature
Project description:We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue.
| S-EPMC3728184 | biostudies-literature
Project description:Human papillomavirus 58 (HPV58) ranks the second or third in East Asian cervical cancers. Current studies on HPV58 are scarce and focus on the prototype. Previously, we identified the three most common circulating HPV58 E7 strains contained amino acid alterations: G41R/G63D (51%), T20I/G63S (22%) and T74A/D76E (14%) respectively. Among them, the T20I/G63S variant (V1) had a stronger epidemiological association with cervical cancer. We therefore suggested that V1 possessed stronger oncogenicity than the other two variants. Here, we performed phenotypic assays to characterize and compare their oncogenicities with HPV58 E7 prototype. Our results showed that overexpression of V1 conferred a higher colony-forming ability to primary murine epithelial cells than prototype (P < 0.05) and other variants, implicating its higher immortalising potential. Further experiments showed that both V1 and prototype enhanced the anchorage-independent growth of NIH/3T3 cells (P < 0.001), implicating their stronger transforming power than the two other variants. Moreover, they possessed an increased ability to degrade pRb (P < 0.001), which is a major effector pathway of E7-driven oncogenesis. Our work represents the first study to compare the oncogenicities of HPV58 E7 prototype and variants. These findings deepened our understanding of HPV58 and might inform clinical screening and follow-up strategy.
| S-EPMC6349171 | biostudies-literature
Project description:The incidence of human papillomavirus (HPV)-positive oropharyngeal cancers is higher and increasing more rapidly among men than women in the United States for unknown reasons. We compared the epidemiology of oral oncogenic HPV infection between men and women ages 14 to 69 years (N = 9,480) within the U.S. National Health and Nutritional Examination Surveys (NHANES) 2009-2012. HPV presence was detected in oral DNA by PCR. Analyses were stratified by gender and used NHANES sample weights. Oral oncogenic HPV prevalence was higher among men than women (6.6% vs. 1.5%, P < 0.001), corresponding to 7.07 million men versus 1.54 million women with prevalent infection at any point in time during 2009-2012. Prevalence increased significantly with age, current smoking, and lifetime number of sexual partners for both genders (adjusted Ptrend < 0.02). However, men had more partners than women (mean = 18 vs. 7, P < 0.001). Although oncogenic HPV prevalence was similar for men and women with 0 to 1 lifetime partners, the male-female difference in prevalence significantly increased with number of lifetime partners (adjusted prevalence differences for none, 1, 2-5, 6-10, 11-20, and 20+ partners = 1.0%, 0.5%, 3.0%, 5.7%, 4.6%, and 9.3%, respectively). Importantly, the per-sexual partner increase in prevalence was significantly stronger among men than among women (adjusted synergy index = 3.3; 95% confidence interval, 1.1-9.7), and this increase plateaued at 25 lifetime partners among men versus 10 partners among women. Our data suggest that the higher burden of oral oncogenic HPV infections and HPV-positive oropharyngeal cancers among men than women arises in part from higher number of lifetime sexual partners and stronger associations with sexual behaviors among men.
| S-EPMC4470779 | biostudies-literature
Project description:OBJECTIVE:Little is known about the interaction between human papillomavirus (HPV) and HIV. This study aimed to explore the association of oncogenic (high risk) and nononcogenic (low risk) HPV with HIV incidence. METHODS:We used 1683 urethral swabs collected at the last follow-up visit of a male circumcision trial conducted in Orange Farm (South Africa). Swabs analyses and HPV genotyping were performed by polymerase chain reaction. We estimated HIV adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) using survival analysis. Background characteristics, male circumcision status, sexual behavior, HPV status, and other sexually transmitted infections were used as covariates. RESULTS:The prevalence of HR and LR HPV was 14.0% (95% CI: 12.4 to 15.7) and 17.3% (95% CI: 15.6 to 19.2), respectively. When controlling for HR-HPV status, LR-HPV status was not associated with HIV incidence (aIRR = 1.13, 95% CI: 0.40 to 3.16; P = 0.82). When controlling for all covariates, HIV incidence increased significantly with HR-HPV positivity (aIRR = 3.76, 95% CI: 1.83 to 7.73, P < 0.001) and with the number of HR-HPV genotypes (adjusted-P linear trend = 0.0074). CONCLUSIONS:Several explanations could account for our findings. One is that HR-HPV facilitates HIV acquisition. The association of HPV with HIV acquisition requires further investigations.
| S-EPMC3203884 | biostudies-literature
Project description:Objectives:Cervical cancer is caused by persistent infection with oncogenic, or "high-risk" types of human papillomaviruses, and is the most common malignancy in Kenyan women. A longitudinal study was initiated to investigate factors associated with persistent human papillomavirus detection among HIV-infected and HIV-uninfected Kenyan women without evidence of cervical dysplasia. Methods:Demographic/behavioral data and cervical swabs were collected from HIV-uninfected women (n?=?82) and HIV-infected women (n?=?101) at enrollment and annually for 2?years. Human papillomavirus typing was performed on swabs (Roche Linear Array). Logistic regression models of human papillomavirus persistence were adjusted for demographic and behavioral characteristics. Results:HIV-infected women were older and less likely to be married and to own a home and had more lifetime sexual partners than HIV-uninfected women. All HIV-infected women were receiving anti-retroviral therapy at enrollment and had satisfactory CD4 cell counts and HIV viral loads. One- and two-year persistent human papillomavirus detection was significantly associated with HIV infection for any human papillomavirus, high-risk human papillomavirus, International Agency for the Research on Cancer-classified high-risk human papillomavirus, and non-oncogenic "low-risk" human papillomavirus. Conclusion:Persistent detection of oncogenic and non-oncogenic human papillomavirus was strongly associated with HIV infection in Kenyan women with re-constituted immune systems based on satisfactory CD4 cell counts. In addition to HIV infection, factors associated with an increased risk of human papillomavirus persistence included a higher number of lifetime sex partners. Factors associated with decreased risk of human papillomavirus persistence included older age and being married. Further studies are needed to identify the immunological defects in HIV-infected women that allow human papillomavirus persistence, even in women receiving effective anti-retroviral therapy. Further studies are also needed to determine the significance of low-risk human papillomavirus persistence in HIV-infected women.
| S-EPMC7388102 | biostudies-literature
Project description:Human papillomavirus (HPV) infection is a prerequisite of developing cervical cancer, approximately half of which are associated with HPV type 16. HPV 16 encodes three oncogenes, E5, E6, and E7, of which E5 is the least studied so far. Its roles in regulating replication and pathogenesis of HPV are not fully understood. Here we utilize high-throughput screening to coordinately investigate the effect of E5 on the expression of host protein-coding and microRNA genes. MicroRNAs form a class of 22nt long noncoding RNAs with regulatory activity. Among the altered cellular microRNAs we focus on the alteration in the expression of miR-146a, miR-203 and miR-324-5p and their target genes in a time interval of 96 hours of E5 induction. Our results indicate that HPV infection and subsequent transformation take place through complex regulatory patterns of gene expression in the host cells, part of which are regulated by the E5 protein.
| S-EPMC3128596 | biostudies-literature
Project description:Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25-65-year-old-female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p < 0.001). Recent sex partners were not significantly associated with viral levels. Compared with prevalent infections detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20-8.45) or single-time (OR = 1.32, 95% CI: 1.03-1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance.
| S-EPMC3947429 | biostudies-literature
Project description:Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.
| S-EPMC5932372 | biostudies-literature