Prognosis of HPV-positive head and neck cancers: implication of smoking and immunosuppression

Duray, Anaelle; Lacremans, Daniel; Demoulin, Stéphanie; Delvenne, Philippe; Saussez, Sven

doi:10.3402/acmo.v2.25717

Cited by 7 publications

(4 citation statements)

References 78 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subgroup of HPV-positive patients seems to have a worse prognosis than others and identifying those patients is clinically important. A recent review paper concludes that discriminating between HPV-positive tumors that are related to smoking and alcohol consumption and those are not related to these risk factors is critical for prognosis analysis (39). Our current data also show that co-existing conditions such as smoking may affect patient outcomes (Table S6 and Table S7).…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Qian

Wang

Magliocca

et al. 2016

European Journal of Cancer

View full text Add to dashboard Cite

Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) carries a distinct clinical behavior. c-Met oncogene is an important driver for tumor progression and its relationship with HPV in OPSCC was explored in the current study. Experimental Design Knockdown of HPV oncogene E6 or p53 alone and in combination was performed to examine their effects on c-Met expression by western blot and qRT-PCR. The effects of c-Met inhibition on cell proliferation, migration, and colony formation were examined in HPV-positive head and neck squamous cell carcinoma (HNSCC) cells. Retrospectively collected OPSCC patient specimens (N = 78) were stained for c-Met by immunohistochemistry and the staining levels were correlated with HPV status and patient outcomes. Results E6 knockdown decreased c-Met protein and mRNA expression in HPV-positive HNSCC cells, which was partially abolished by the elimination of p53. Reducing c-Met decreased cell proliferation, migration, and colony formation in HPV-positive HNSCC cells. In OPSCC patient samples, high c-Met expression was associated with HPV positive status (OR = 4.11, 95%CI: 1.16–14.55, P = 0.028) and tumor stage (OR = 0.27, 95%CI: 0.08–0.93, P = 0.039) by multivariable analysis. In T3/T4 stage patients, high c-Met expression was associated with HPV positivity and low p53 levels, supporting an axis of E6-p53-c-Met regulation. Furthermore, high c-Met expression was marginally associated with poor disease-free survival in HPV-positive patients. Conclusions Our results suggest that c-Met may serve as a novel target for treating HPV-associated OPSCC. The data also demonstrates that HPV E6 upregulates c-Met expression partially through p53 downregulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Qian

Wang

Magliocca

et al. 2016

European Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…HNSCC patients presenting early clinical stages have a 5 year survival rate of 70-90%, whilst 50% of HNSCC patients presenting advanced clinical stages die within 2 years following the initial diagnosis 56 . With HPV on the rise, one of the major clinical challenges for managing HNSCC today is the lack of early screening/diagnostic methods.…”

Section: Future Outlookmentioning

confidence: 99%

Oral Microbiome: A New Biomarker Reservoir for Oral and Oropharyngeal Cancers

Lim¹,

Totsika²,

Morrison³

et al. 2017

Theranostics

115

View full text Add to dashboard Cite

Current biomarkers (DNA, RNA and protein) for oral cavity and oropharyngeal cancers demonstrate biological variations between individuals, rendering them impractical for clinical translation. Whilst these biomarkers originate from the host, there is not much information in the literature about the influence of oral microbiota on cancer pathogenesis, especially in oral cancers. Oral microbiotas are known to participate in disease initiation and progression not only limited to the oral cavity, but also at other distant sites. Due to the close proximity of oral microbiota and oral cavity and oropharyngeal tumours, abundance changes in oral microbiota may provide useful information on tumourigenesis. This review aims to highlight information on the role of oral microbiota in oral cavity and oropharyngeal cancers. An in-depth analysis into the oral microbiota may provide a new avenue to diagnose and treat these patients.

show abstract

“…A meta-analysis by Ragin and Taioli (2007) showed no survival difference between HPV-positive and HPV-negative patients with cancer at nonoropharyngeal sites of the head and neck, including oral cavity. The source of the discrepancy in outcome between the oropharynx and oral cavity is not entirely clear, but differences in immune response from site to site may be an important factor (Duray et al 2014).…”

Section: Figure 2 E6 and E7 Induce Replication By Blocking The Functmentioning

confidence: 99%

Human Papillomavirus Genome Integration and Head and Neck Cancer

2017

View full text Add to dashboard Cite

We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

show abstract

Prognosis of HPV-positive head and neck cancers: implication of smoking and immunosuppression

Cited by 7 publications

References 78 publications

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Oral Microbiome: A New Biomarker Reservoir for Oral and Oropharyngeal Cancers

Human Papillomavirus Genome Integration and Head and Neck Cancer

Contact Info

Product

Resources

About