Tobacco exposure results in increased E6 and E7 oncogene expression, DNA damage and mutation rates in cells maintaining episomal human papillomavirus 16 genomes

Wei, Lanlan; Griego, Anastacia; Chen, Ming; Ozbun, Michelle A.

doi:10.1093/carcin/bgu156

Cited by 34 publications

(43 citation statements)

References 62 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…37 Decreased immune responses in conjunction with higher HPV viral load may lead to increased risk of viral acquisition or persistence. 38 We also observed that current smoking, but not former smoking, was positively associated with HPV viral load. These findings are consistent with a previous study measuring HPV-16 and HPV-18 viral load, where the enrollment viral load was found to be greater among current smokers when compared with never smokers, 39 but inconsistent with our previous study among high-risk mid-adult women, where viral load was higher in never or former smokers compared with current smokers.…”

Section: Discussionsupporting

confidence: 59%

“…Possible mechanisms through which smoking may facilitate acquisition or persistence of HPV may be the reduction of Langerhans cells and CD4 lymphocytes, as well as the inactivation of natural killer cells . Decreased immune responses in conjunction with higher HPV viral load may lead to increased risk of viral acquisition or persistence . We also observed that current smoking, but not former smoking, was positively associated with HPV viral load.…”

Section: Discussionmentioning

confidence: 52%

See 1 more Smart Citation

Short‐term natural history of high‐risk human papillomavirus infection in mid‐adult women sampled monthly

Hulbert

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

Characterizing short-term HPV detection patterns and viral load may inform HPV natural history in mid-adult women. From 2011–2012, we recruited women aged 30–50 years. Women submitted monthly self-collected vaginal samples for high-risk HPV DNA testing for 6 months. Positive samples were tested for type-specific HPV DNA load by real-time PCR. HPV type-adjusted linear and Poisson regression assessed factors associated with 1) viral load at initial HPV detection and 2) repeat type-specific HPV detection. One-hundred thirty-nine women (36% of 387 women with ≥4 samples) contributed 243 type-specific HR HPV infections during the study; 54% of infections were prevalent and 46% were incident. Incident (versus prevalent) detection and past pregnancy were associated with lower viral load, whereas current smoking was associated with higher viral load. In multivariate analysis, current smoking was associated with a 40% (95%CI:5%–87%) increase in the proportion of samples that were repeatedly positive for the same HPV type, whereas incident (versus prevalent) detection status and past pregnancy were each associated with a reduction in the proportion of samples repeatedly positive (55%,95%CI:38%–67% and 26%,95%CI:10%–39%, respectively). In a separate multivariate model, each log10 increase in viral load was associated with a 10% (95%CI:4%–16%) increase in the proportion of samples repeatedly positive. Factors associated with repeat HPV detection were similar to those observed in longer-term studies, suggesting that short-term repeat detection may relate to long-term persistence. The negative associations between incident HPV detection and both viral load and repeat detection suggest that reactivation or intermittent persistence was more common than new acquisition.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 52%

Short‐term natural history of high‐risk human papillomavirus infection in mid‐adult women sampled monthly

Hulbert

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…An immune mechanism behind the effect of smoking on hrHPV infection would most probably imply an effect early in the natural history of the infection, by preventing the virus -host cell membrane interaction, and not on later stages including integration and subsequent expression of viral proteins. This theory is supported by the findings of Wei et al, (2014) in tobacco-exposed cervical cell lines, describing loss of p53 activity and increased E6/E7 oncogene expression only in cells with episomal hrHPV genomes and not in those with integrated viral genomes [24]. In our subanalysis, the non-significant effect of smoking on the detection of E7 protein, an indicator of viral genome integration in vivo, supports further the suggestion, that cigarette smoking has a more prominent role in earlier stages of HPV-related carcinogenesis.…”

Section: Discussionsupporting

confidence: 57%

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression

Chatzistamatiou

Moysiadis

Vryzas

et al. 2018

Preprint

View full text Add to dashboard Cite

Persistent cervical infection with high-risk Human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. In order to assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95%CI: 1.365-2.332, p<0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

show abstract

“…55 MSTS-C caused a dose-dependent increase in viral replication in cells with episomal HPV by inducing E6 oncogene transcription and decreasing p53 protein levels. Loss of p53 activity in tobacco-exposed cells led to significantly higher DNA strand breaks, and DNA mutation frequencies were higher in surviving cells with HPV episomes, indicating that tobacco smoke can directly alter HPV oncogene expression in the presence of episomal HPV.…”

Section: Hpv and Tobaccomentioning

confidence: 96%

Human Papillomavirus–Associated Oropharyngeal Cancer: Defining Risk Groups and Clinical Trials

Bhatia

Burtness

2015

JCO

119

101

View full text Add to dashboard Cite

Human papillomavirus–associated oropharynx cancer (HPVA-OPC) is rapidly increasing in incidence and has unique epidemiologic, molecular, and biologic characteristics. Despite being recognized as having superior prognosis, current evidence does not support less intense therapy compared with HPV-negative OPC. Current combined modality therapies confer a significant risk of morbidity, and patients with HPVA-OPC have a younger median age. These patients, therefore, live longer with the adverse effects of treatment, and this spurs the development of treatment deintensification trials that attempt to decrease treatment-related morbidity without compromising efficacy. Many radiation and chemotherapy de-escalation trials are underway. Minimally invasive surgical techniques are also being evaluated. It is important to identify the ideal patient group for treatment deintensification and to define prognostic risk groups to avoid undertreating the poorer-risk subset in HPVA-OPC, and validated biomarkers are needed to identify patients with the best prognosis. Significant smoking exposure mitigates the favorable prognosis of HPVA-OPC. Currently, less intense treatment is an option only in the setting of clinical trials, and patients with HPVA-OPC should be offered clinical trial options whenever they are available. Finally, recognition of novel therapeutic targets and signaling pathways is critical to the development of new treatment strategies that are desperately needed for patients with poor risk and those with recurrent and metastatic disease.

show abstract

Tobacco exposure results in increased E6 and E7 oncogene expression, DNA damage and mutation rates in cells maintaining episomal human papillomavirus 16 genomes

Cited by 34 publications

References 62 publications

Short‐term natural history of high‐risk human papillomavirus infection in mid‐adult women sampled monthly

Short‐term natural history of high‐risk human papillomavirus infection in mid‐adult women sampled monthly

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression

Human Papillomavirus–Associated Oropharyngeal Cancer: Defining Risk Groups and Clinical Trials

Contact Info

Product

Resources

About