HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis

Pan, Cassie; Issaeva, Natalia; Yarbrough, Wendell G.

doi:10.1186/s41199-018-0039-3

Cited by 93 publications

(101 citation statements)

References 85 publications

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“…Standard treatment for OPSCC includes radiation and chemotherapy, which are associated with dose-related morbidities. Patients with papillomavirus-associated oropharyngeal tumors have a better prognosis than those with HPV− OPSCC [21]. HPV+ OPSCC is generally more sensitive to treatment and may respond to de-escalated treatments.…”

Section: Discussionmentioning

confidence: 99%

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A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

Bilger

King

Schroeder

et al. 2020

Viruses

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Human head and neck cancers that develop from the squamous cells of the oropharynx (Oropharyngeal Squamous Cell Carcinomas or OPSCC) are commonly associated with the papillomavirus infection. A papillomavirus infection-based mouse model of oropharyngeal tumorigenesis would be valuable for studying the development and treatment of these tumors. We have developed an efficient system using the mouse papillomavirus (MmuPV1) to generate dysplastic oropharyngeal lesions, including tumors, in the soft palate and the base of the tongue of two immune-deficient strains of mice. To maximize efficiency and safety during infection and endoscopy, we have designed a nose cone for isoflurane-induced anesthesia that takes advantage of a mouse’s need to breathe nasally and has a large window for oral manipulations. To reach and infect the oropharynx efficiently, we have repurposed the Greer Pick allergy testing device as a virus delivery tool. We show that the Pick can be used to infect the epithelium of the soft palate and the base of the tongue of mice directly, without prior scarification. The ability to induce and track oropharyngeal papillomavirus-induced tumors in the mouse, easily and robustly, will facilitate the study of oropharyngeal tumorigenesis and potential treatments.

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Section: Discussionmentioning

confidence: 99%

“…HPV+ OPSCC is generally more sensitive to treatment and may respond to de-escalated treatments. However, treatment for HPV+ and HPV− OPSCC is almost identical [21]. Treatments tailored to the unique etiology of HPV+ disease can be tested using our infection-based model of papillomavirus tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

Bilger

King

Schroeder

et al. 2020

Viruses

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“…et al and Lu S. et al study [41,42] showed that Canter immunotherapy could be applied together with chemotherapy for HNSCC patients according to HPV status, and further studies of the new biomarkers-immunological, genetic, or molecular-are needed to be initiated to provide novel targets for improvement of HPV associated HNSCC patient therapy. In addition, markers to identify HPV-positive laryngeal cancer patients with improved prognosis are emerging [43]. These insights are critical to improving our management of this rising disease and exploring effective new treatments.…”

Section: Discussionmentioning

confidence: 99%

Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

Stumbrytė-Kaminskienė

Gudlevičienė

Dabkevičienė

et al. 2020

Medicina

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Background and objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. The molecular mechanism of LSCC remains unclear. The aim of this study was to evaluate the prevalence of Human papillomavirus (HPV) and single nucleotide polymorphisms (SNPs) of TP53, MDM2, MDM4, MTHFR, CASP8, and CCR5 genes in LSCC, and to assess their correlations with patient survival. Materials and Methods: 49 LSCC patients were enrolled in this study. PCR and qRT-PCR were used to detect, identify, and quantify HPV. SNPs were genotyped using PCR and PCR-RFLP. Results: By analyzing the interactions of the SNPs of the genes with clinical parameters, the majority of patients with lymph node status (N1,2) were identified as carriers of MDM2 T/G, CASP8 ins/del, CCR5 wt/wt SNP. Cluster analysis showed that patients with MDM2 T/T SNP survive longer than patients identified as CASP8 ins/ins, MTHFR C/C, and MDM4 A/A variant carriers; meanwhile, LSCC patients with MDM2 T/T polymorphic variant had the best survival. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring CASP8 ins/del variant had the best survival. Meanwhile, HPV-negative patients with identified metastasis in lymph nodes (N1 and N2) and CASP8 ins/del variant had poor survival. Conclusions: This finding suggests patients survival prognosis and tumor behavior are different according HPV status, SNP variants, and clinical characteristics of the LSCC.

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“…The infection causes changes in the DNA-repair pathways, mitogenic signaling pathways, cell cycle control, and tumor microenvironment. Molecular heterogeneity within HPV(+) tumors predicts better treatment response [ 8 ]. Biological and treatment responses differ between HPV(+) and HPV(−) patients, which might be associated with heterogeneous epigenetic changes in DNA methylation and the functions of non-coding RNAs, such as miRNAs or lncRNAs [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

et al. 2020

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Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.

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HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis

Cited by 93 publications

References 85 publications

A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia

Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

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