HPV in non-oropharyngeal head and neck cancer: does it matter?
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ABSTRACT:
SUBMITTER: Schmitt NC
PROVIDER: S-EPMC7576011 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
HPV in non-oropharyngeal head and neck cancer: does it matter?
Annals of translational medicine 20200901 18
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Project description:HPV-positive squamous oropharyngeal carcinomas (OPCs) have a more positive prognosis compared to HPV-negative OPCs. Nevertheless, the prognosis of some of these tumors is dismal, and currently there are no established prognostic biomarkers in clinical practice. Our study is aimed at evaluating the performances of gene expression signatures that have been previously reported.
2025-02-19 | GSE262372 | GEO
Project description:The prognosis of HPV-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than that of HPV-negative OPCs. However, the prognosis of some of these tumors is dismal and to date validated survival predictors are missing in clinical practice. We designed a study on HPV-positive OPCs to determine whether a previously published gene expression tumor classification model,defined through meta-analysis of publicly available datasets (PMCID: PMC6721309), is able to predict survival in an external patient cohort. The 3 gene expression clusters were tested in a validation set of 286 cases and in a refined study population of 235 patients and in both confirmed their prognostic value. Five-year OS was 95% in the low risk cluster Cl1, 80% in the intermediate risk cluster (HR=5.74, p=.0057), and 66% in the high risk cluster (HR=9.28, p=.001). Functional/biological cluster characterization identified potentially targetable pathways in the high risk cluster. This prognostic stratification might be useful for clinical decision making and for planning future trials based on molecular tumor features.
2021-11-03 | GSE163173 | GEO
Project description:HPV-related oropharyngeal head and neck cancer (gene-expression)
| PRJNA1091612 | ENA
Project description:Head and neck cancers (HNCs) are a highly heterogeneous group of tumours that are associated with diverse clinical outcomes. Recent evidence has demonstrated that human papillomavirus (HPV) is involved in up to 25% of HNCs; particularly in the oropharyngeal carcinoma (OPC) subtype where it can account for up to 60% of such cases. HPVs are double-stranded DNA viruses that infect epithelial cells; numerous HPV subtypes, including 16, 18, 31, 33, and 35, drive epithelial cell transformation and tumourigenesis. HPV positive (HPV+) HNC represents a distinct molecular and clinical entity from HPV negative (HPV-) disease; the biological basis for which remains to be fully elucidated. HPV positivity is strongly correlated with a significantly superior outcome; indicating that such tumours should have a distinct management approach. This review focuses on the recent scientific and clinical investigation of HPV+ HNC. In particular, we discuss the importance of molecular and clinical evidence for defining the role of HPV in HNC, and the clinical impact of HPV status as a biomarker for HNC.
| S-EPMC4999784 | biostudies-literature
Project description:Human papilloma virus (HPV)-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) have different molecular and biologic characteristics and clinical behavior compared with HPV-negative (HPV-) OPSCC. PIK3CA mutations are more common in HPV(+) OPSCC. To define molecular differences and tumor subsets, protein expression and phosphorylation were compared between HPV(+) and HPV(-) OPSCC and between tumors with and without PIK3CA mutations.Expression of 137 total and phosphorylated proteins was evaluated by reverse-phase protein array in 29 HPV(+) and 13 HPV(-) prospectively collected OPSCCs. Forty-seven OPSCCs were tested for hotspot-activating mutations in PIK3CA and AKT. Activation of PIK3CA downstream targets and sensitivity to pathway inhibitors were determined in HPV(+) head and neck cancer cells overexpressing wild-type or mutant PIK3CA.Analyses revealed 41 differentially expressed proteins between HPV(+) and HPV(-) OPSCC categorized into functional groups: DNA repair, cell cycle, apoptosis, phosphoinositide 3-kinase (PI3K)/AKT/mTOR, and receptor kinase pathways. All queried DNA repair proteins were significantly upregulated in HPV(+) samples. A total of 8 of 33 HPV(+) and 0 of 14 HPV(-) tumors contained activating PIK3CA mutations. Despite all activating PIK3CA mutations occurring in HPV(+) samples, HPV(+) tumors had lower mean levels of activated AKT and downstream AKT target phosphorylation. Ectopic expression of mutant PIK3CA in HPV(+) cells increased mTOR, but not AKT activity. HPV E6/E7 overexpression inhibited AKT phosphorylation in HPV-negative cells. Mutant PIK3CA overexpressing cells were more sensitive to a dual PI3K/mTOR inhibitor compared with an AKT inhibitor.Protein expression analyses suggest that HPV(+) and HPV(-) OPSCC differentially activate DNA repair, cell cycle, apoptosis, PI3K/AKT/mTOR, and receptor kinase pathways. PIK3CA mutations are more common in HPV(+) OPSCC and are associated with activation of mTOR, but not AKT. These data suggest that inhibitors for mTOR may have activity against HPV(+) PIK3CA mutant oropharyngeal cancers.
| S-EPMC4027970 | biostudies-other
Project description:Gene expression profiling in HPV-infected oropharyngeal head and neck cancer
| PRJNA685147 | ENA
Project description:BACKGROUND: Although tobacco- and alcohol-associated head and neck cancers are declining in the developed world, potentially human papillomavirus (HPV)-associated oropharnygeal cancers are increasing. METHODS: We analysed oropharyngeal and oral cavity cancer rates in Australia in 1982-2005. Cancers from the oropharynx (base of tongue, tonsil and other specific oropharyngeal sites) were classified as potentially HPV associated (n=8844); cancers in other oral cavity and oropharyngeal sites not previously associated with HPV were classified as comparison (n=28,379). RESULTS: In 2000-2005, an average of 219, 159 and 110 cancers of the tonsil, base of tongue and other oropharyngeal sites were diagnosed annually, with incidences of 1.09 (95% CI: 1.03, 1.15), 0.79 (95% CI: 0.74, 0.84) and 0.55 (95% CI: 0.50, 0.59) per 100,000, respectively. An average of 1242 comparison cancers were diagnosed annually (6.17 (95% CI: 6.03, 6.31) per 100,000). In 1982-2005, there were significant annual increases in tonsil (1.39% (95% CI: 0.88, 1.92%)) and base of tongue cancers in males (3.02% (95% CI: 2.27, 3.78%)) and base of tongue cancer in females (3.45% (95% CI: 2.21, 4.70%)). There was a significant decrease in comparison cancers in men (-1.69% (95% CI: -1.96, -1.42%)), but not in females. CONCLUSION: Potentially HPV-associated oropharyngeal cancer in Australia is increasing; the impact of HPV vaccination on these cancers should be monitored.
| S-EPMC3048203 | biostudies-other
Project description:IntroductionSeveral aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.MethodsHaCaT and HeLa cell lines were used to investigate the effects of shRNA transfection and nicotine exposure on HPV16-PsV-uptake. Cells were treated with Lipofectamine™ RNAiMAX for 48 or 72 hours with specific shRNA-concentrations, while nicotine was added to the cell medium at the indicated concentrations. Protein isolation, SLPI- and AnxA2-quantification, LDH cytotoxicity assessment, HPV16-PsV-uptake measurement, mRNA-isolation, cDNA-synthesis and RT-qPCR were performed.ResultsIn vitro transfection experiments with HPV16 pseudovirions (PsVs) showed that PsVs entered cells significantly better when SLPI was downregulated and significantly less when AnxA2 was downregulated. Nicotine exposure increased SLPI levels and reduced PsV uptake.ConclusionsThe overexpression of SLPI caused by tobacco-smoking can hinder HPV cell entry by binding to AnxA2 and thus prevent successful HPV infection. Conversely, non-smokers have lower SLPI-levels, associated with an excess of unbound AnxA2, favoring HPV cell-entry. These findings support our hypothesis, suggesting a paradigm shift in understanding virus-related pathogenesis, particularly in the head and neck region, and the nature of HPV infection.
| S-EPMC11754403 | biostudies-literature
Project description:Opinion statementThe rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.
| S-EPMC8178129 | biostudies-literature
Project description:Integration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC). Whole-genome sequencing of 51 tumors revealed intratumor heterogeneity of HPV integration, with 44% of breakpoints subclonal, and a biased distribution of integration breakpoints across the HPV genome. Four HPV physical states were identified, with at least 49% of tumors progressing without integration. HPV integration was associated with APOBEC-induced broad genomic instability and focal genomic instability, including structural variants at integration sites. HPV+ HNSCCs exhibited almost no smoking-induced mutational signatures. Heterozygous loss of ataxia-telangiectasia mutated (ATM) was observed in 67% of tumors, with its downregulation confirmed by single-cell RNA sequencing and immunohistochemistry, suggesting ATM haploinsufficiency contributes to carcinogenesis. PI3K activation was the major oncogenic mutation, with JAK-STAT activation in tumors with clonal integration and NF-kappa B activation in those without. These findings provide valuable insights into HPV integration in HPV+ HNSCC.
| S-EPMC11770129 | biostudies-literature