Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact of HPV status on HNSCC metabolism remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique to HPV-positive HNSCC influences patient survival. The Cancer Genome Atlas RNA-seq data from primary HNSCC patient samples were categorized as 73 HPV-positive, 442 HPV-negative, and 43 normal-adjacent control tissues. We analyzed 229 metabolic genes and identified numerous differentially expressed genes between HPV-positive and negative HNSCC patients. HPV-positive carcinomas exhibited lower expression levels of genes involved in glycolysis and higher levels of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and β-oxidation than the HPV-negative carcinomas. Importantly, reduced expression of the metabolism-related genes SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, and SLC16A2 were correlated with improved patient survival only in the HPV-positive group. This work suggests that specific transcriptional alterations in metabolic genes may serve as predictive biomarkers of patient outcome and identifies potential targets for novel therapeutic intervention in HPV-positive head and neck cancers.

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Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm7120501 ◽

2018 ◽

Vol 7 (12) ◽

pp. 501 ◽

Cited By ~ 6

Author(s):

Francisco Hermida-Prado ◽

Sofía Menéndez ◽

Pablo Albornoz-Afanasiev ◽

Rocío Granda-Diaz ◽

Saúl Álvarez-Teijeiro ◽

...

Keyword(s):

Protein Expression ◽

Head And Neck ◽

Gene Amplification ◽

Hpv Infection ◽

The Cancer Genome Atlas ◽

Hpv Status ◽

The Status ◽

Impact On Survival ◽

Cancer Genome Atlas ◽

The Impact

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39–46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients.

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Diagnosis and treatment delay of head and neck cancers during COVID-19 era in a tertiary care academic hospital: what should we expect?

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-021-06834-1 ◽

2021 ◽

Author(s):

Pietro De Luca ◽

Antonella Bisogno ◽

Vito Colacurcio ◽

Pasquale Marra ◽

Claudia Cassandro ◽

...

Keyword(s):

Retrospective Study ◽

Head And Neck ◽

Retrospective Analysis ◽

Tertiary Care ◽

Diagnostic Delay ◽

Treatment Delay ◽

Head And Neck Cancers ◽

Control Measures ◽

Academic Hospital ◽

The Impact

Abstract Background Since the spreading of SARS-CoV-2 from China, all deferrable medical activities have been suspended, to redirect resources for the management of COVID patients. The goal of this retrospective study was to investigate the impact of COVID-19 on head and neck cancers’ diagnosis in our Academic Hospital. Methods A retrospective analysis of patients treated for head and neck cancers between March 12 and November 1, 2020 was carried out, and we compared these data with the diagnoses of the same periods of the 5 previous years. Results 47 patients were included in this study. We observed a significative reduction in comparison with the same period of the previous 5 years. Conclusions Our findings suggest that the COVID-19 pandemic is associated with a decrease in the number of new H&N cancers diagnoses, and a substantial diagnostic delay can be attributable to COVID-19 control measures.

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Psychosocial outcomes of human papillomavirus (HPV)‐ and non‐HPV‐related head and neck cancers: A longitudinal study

Psycho-Oncology ◽

10.1002/pon.5803 ◽

2021 ◽

Author(s):

Melissa Henry ◽

Emily Arnovitz ◽

Saul Frenkiel ◽

Michael Hier ◽

Anthony Zeitouni ◽

...

Keyword(s):

Human Papillomavirus ◽

Longitudinal Study ◽

Head And Neck ◽

Psychosocial Outcomes ◽

Head And Neck Cancers

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Relationship Between Human Papillomavirus (HPV) Status, Epidermal Growth Factor Receptor (EGFR) and Phospho-EGFR (pEGFR) Expression in Head and Neck Squamous Cell Carcinoma (HNSCC)

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2008.06.817 ◽

2008 ◽

Vol 72 (1) ◽

pp. S23

Author(s):

E.J. Filion ◽

C.S. Kong ◽

B. Narasimhan ◽

H. Cao ◽

J.P. Erickson ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Epidermal Growth Factor Receptor ◽

Human Papillomavirus ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cell Carcinoma ◽

Head And Neck ◽

Growth Factor Receptor ◽

Hpv Status ◽

Epidermal Growth

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Comorbidity and prognosis in head and neck cancers: Differences by subsite, stage, and human papillomavirus status

Head & Neck ◽

10.1002/hed.23360 ◽

2013 ◽

Vol 36 (6) ◽

pp. 802-810 ◽

Cited By ~ 49

Author(s):

Steven Habbous ◽

Luke T. G. Harland ◽

Anthony La Delfa ◽

Ehab Fadhel ◽

Wei Xu ◽

...

Keyword(s):

Human Papillomavirus ◽

Head And Neck ◽

Head And Neck Cancers

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Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates

Sexually Transmitted Infections ◽

10.1136/sextrans-2018-053606 ◽

2018 ◽

Vol 95 (1) ◽

pp. 28-35 ◽

Cited By ~ 2

Author(s):

Koh Jun Ong ◽

Marta Checchi ◽

Lorna Burns ◽

Charlotte Pavitt ◽

Maarten J Postma ◽

...

Keyword(s):

Systematic Review ◽

Human Papillomavirus ◽

Head And Neck ◽

Anal Cancer ◽

Penile Cancer ◽

Vulvar Cancer ◽

Head And Neck Cancers ◽

Economic Evaluations ◽

Anogenital Warts ◽

Utility Elicitation

BackgroundMany economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews.MethodsWe conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider’s perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$.ResultsSixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124–US$883 (anogenital warts), US$6912–US$52 579 (head and neck cancers), US$12 936–US$51 571 (anal cancer), US$17 524–34 258 (vaginal cancer), US$14 686–US$28 502 (vulvar cancer) and US$9975–US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer).ConclusionsDifferences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.

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Genotype Distribution and Prevalence of Human Papillomavirus in Head and Neck Cancer Samples from Istanbul, Turkey

Pathogens ◽

10.3390/pathogens10121533 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1533

Author(s):

Muammer Osman Köksal ◽

Başak Keskin Yalçın ◽

Fahriye Keskin ◽

Sevgi Çiftçi ◽

Ibrahim Yağcı ◽

...

Keyword(s):

Human Papillomavirus ◽

Head And Neck ◽

Significant Proportion ◽

Developed Countries ◽

Genotype Distribution ◽

Hpv Dna ◽

P16ink4a Expression ◽

Hpv Status ◽

Tumor Biopsies ◽

Turkish Patients

Human papillomavirus (HPV)-associated tumors account for a significant proportion of head and neck squamous cell carcinomas (HNSCC) in developed countries. In recent years, there has been a rise of HPV infections associated with HNSCC, especially HPV16, which is the most commonly detected type in oral and oropharyngeal cancers. To investigate the frequency of HPV-driven HNSCC among patients living in Turkey, HPV DNA positivity and p16INK4A expression were assessed in primary tumor biopsies (n = 106). Eighteen out of one hundred and six (19%) HNSCC tumors showed p16INK4A overexpression, and 26/106 cases (24.5%) were positive for HPV DNA. Sixteen out of twenty-six samples were positive for both HPV DNA and p16INK4A staining. HPV16 could be isolated from 22/26 samples (84.6%) and was found to be the most frequently detected HPV type. This study represents the largest cohort of Turkish patients with HNSCC characterized according to HPV status and p16INK4A expression. Our data suggest that HPV16 infection, along with smoking, contribute to the development of HNSCC.

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Use of a Linear Array for the Detection of Human Papillomavirus Genotypes in Head and Neck Cancer

Archives of Pathology & Laboratory Medicine ◽

10.5858/2009-0592-oar.1 ◽

2010 ◽

Vol 134 (12) ◽

pp. 1813-1817

Author(s):

Candice C. Black ◽

Heather A. Bentley ◽

Thomas H. Davis ◽

Gregory J. Tsongalis

Keyword(s):

Human Papillomavirus ◽

Head And Neck ◽

Linear Array ◽

Hpv Genotyping ◽

Formalin Fixed Paraffin ◽

Hpv Status ◽

Test Kit ◽

Formalin Fixed Paraffin Embedded ◽

Roche Linear Array ◽

Formalin Fixed

Abstract Context—Tumors of the head and neck commonly arise from the squamous and respiratory mucosa that lines the nasal and oral cavity, sinuses, pharynx, and larynx. The rate of oropharyngeal cancers diagnosed among Americans younger than 50 years is increasing. Infection of the oropharynx and tonsils by the human papillomavirus (HPV) has been linked to preneoplasia and cancer. Objectives—To evaluate the Roche Linear Array HPV Genotyping test kit to identify, and then specifically genotype, HPV in formalin-fixed, paraffin-embedded tissues. Design—We evaluated the performance of this assay for accuracy, for intra-assay and interassay precision, and for its limit of detection, using materials with known HPV status. Sixteen tumor tissues with the following origins were evaluated: 1 ocular, 1 hypopharynx, 8 tonsil, 1 retromolar trigone, 3 tongue, 1 anal, and 1 lymph node. DNA from formalin-fixed, paraffin-embedded tumor sections was isolated and amplified in duplicate, with positive and negative controls, using primers specific to the polymorphic L1 region of the HPV genome. Thirty-seven genotypes were tested using the linear array. The amplified product (450 base pairs) was visualized by gel electrophoresis and, if positive, reflexed to HPV genotyping. Results—Nine of the 16 tumors analyzed were HPV positive. The detected genotypes included HPV 6, 16, and 69. Conclusions—The Roche Linear Array HPV Genotyping test is an easy-to-use method for determining HPV genotype in the routine analysis of formalin-fixed, paraffin-embedded tumors. This assay is robust and can be performed routinely in a clinical laboratory setting.

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