Human papillomavirus in carcinomas of the tongue: clinical and prognostic implications

Marcos, José Antonio García-De; Pérez-Zafrilla, Beatriz; Arriaga, Á.; Arroyo-Rodrı́guez, Susana; Poblet, Enrique

doi:10.1016/j.ijom.2013.10.016

Cited by 12 publications

(11 citation statements)

References 43 publications

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“…A recent study in Europe showed 26% of HPV prevalence in oral tongue tumors [45, 46]. Contrary to the data from the United States [48, 49] and closer to the HPV data from Europe [50], studies from India previously reported a high prevalence of HPV in oral cavity tumors, including in oral tongue (anywhere between 18–51% depending on the HPV detection assay used) [51, 52]. Although the reason(s) and importance for such a high prevalence of HPV in our geography is currently not known, the association of HPV with well-differentiated squamous cell carcinoma of oral cavity has been reported in the past [51] in contrast to the oropharyngeal tumors.…”

Section: Discussionmentioning

confidence: 80%

Integrated analysis linksTP53, NOTCH, SLC38Aand 11p with survival in patients with oral tongue squamous cell carcinoma

Gupta

Khyriem

et al. 2015

Preprint

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15Head and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of cancers 16 affecting multiple subsites, including oral cavity. Oral or anterior tongue tumors (OTSCC) are an 17 aggressive group of squamous cell carcinomas, characterized by their early spread to lymph nodes 18 and higher rate of regional failure compared to other oral cavity cancers. There is a rise in the 19 incidence of oral tongue cancer among younger population (<50yrs); many of who lack the typical 20 associated risk factors of alcohol and/or tobacco exposure. In order to carry out an ensemble 21 learning and prediction method with multiple parameters classifying survival, we generated data, on 22 somatic mutations in genes from exome sequencing, immediate upstream and downstream flanking 23 nucleotides of the somatic mutations, DNA methylation, loss of heterozygosity (LOH), copy 24 number variations (CNV), gene expression, significant pathways altered and Human Papilloma 25 Virus (HPV) infection, from 50 OTSCC patients. Results of our analysis identified somatic 26 mutations in NOTCH2 and/or TP53, and/or LOH in 11p to associate with better disease free 27 survival in HPV positive patients (P = 0.0254) and not in HPV negative patients (P = 0.414). We 28 validated the latter in patients without HPV infection from TCGA cohort (P = 0.369, N = 17 for 29 2 TCGA_ OralTongue; P = 0.472, N = 67 for all TCGA_HNSCC patients). Integrated analysis, 30 including pathways, linked survival with apoptosis and aberrant methylation in SLC38A8 (P = 31 0.0129). 32 33 Author Summary 34 Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of head and neck 35 tumors characterized with aggressive behavior among younger patients. In this report, we have 36 analysed genetic variants, expression and DNA methylation changes across 50 oral tongue primary 37 tumors along with the Human Papilloma Virus (HPV) infection status in those tumors to identify 38 factors associated with disease free survival. Our data identified somatic mutations in the genes 39 NOTCH2, TP53 and LOH in 11p, to be significantly associated with better disease free survival in 40 HPV positive patients (P = 0.0254), but not in HPV negative patients (P = 0.414). We validated the 41 latter using patients without HPV infection from TCGA (P = 0.369, N = 17 for 42 TCGA_OralTongue; P = 0.472, N = 67 for all TCGA_HNSCC patients). Integrated analysis linked 43 survival with apoptosis and aberrant methylation in SLC38A8 (P = 0.0129).44 45 48 cause of cancer worldwide [1]. In India, they account for almost 30% of all cancer cases [2]. Studies 49 on molecular biology of HNSCC in the past 5yrs have largely been concentrated on cataloging 50various genetic changes in many cancer types using high-throughput sequencing assays and 51 computational methods [3][4][5][6][7]. Unlike other oral cavity subsites, squamous cell carcinomas of 52 oral/anterior tongue tend to be associated more with younger patients [8, 9], early spread to lymph 53 nodes [8] and a higher regional failure compared t...

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Section: Discussionmentioning

confidence: 80%

Integrated analysis linksTP53, NOTCH, SLC38Aand 11p with survival in patients with oral tongue squamous cell carcinoma

Gupta

Khyriem

et al. 2015

Preprint

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“…During this process, cancer precursor lesions can be morphometrically recognized [ 7 ]. Various different biomarker studies have been reported to date [ 5 – 10 ]. Nakabayashi et al [ 5 ] have suggested that paired-like homeodomain 1 (PITX1) suppression is associated with OED malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the feasibility of using markers such as cyclin D1, p27, and p53 as predictors of OED malignant transformation have also been investigated [ 7 ]. Recently, a correlation between high human papilloma virus expression and oral malignancy was also reported [ 9 , 10 ]. However, some of these markers require sample analysis using PCR, real time-PCR, or in situ hybridization [ 8 – 10 ], but simple techniques using routine formalin-fixed paraffin-embedded biopsy specimens are required.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a correlation between high human papilloma virus expression and oral malignancy was also reported [ 9 , 10 ]. However, some of these markers require sample analysis using PCR, real time-PCR, or in situ hybridization [ 8 – 10 ], but simple techniques using routine formalin-fixed paraffin-embedded biopsy specimens are required. Therefore, we have focused on NAC1 immunohistochemistry to evaluate its potential as a marker for distinguishing between OED and CIS/OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, more than a third of OSCC patients present with OED in close proximity. Various biological markers for malignant transformation and OED progression have been reported [ 5 – 10 ]. However, for maxillofacial surgeons, OED and SIN are both candidate lesions for resection, and given the aforementioned background, a simple and feasible marker for distinguishing OED from malignancy is required for application in routine work.…”

Section: Introductionmentioning

confidence: 99%

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Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma

et al. 2015

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BackgroundOral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC.Methods and FindingsThe study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients’ pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11–1.28], p < 0.001) and NAC1 IRI (0.78 [0.68–0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC.ConclusionsNAC1 has potential as a marker for distinguishing OED from CIS/OSCC.

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The Prognostic Value of Human Papilloma Virus Infection in Oral Cavity Squamous Cell Carcinoma: A Meta‐Analysis

Christianto

Huang

et al. 2021

The Laryngoscope

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Objectives/Hypothesis: Human papilloma virus (HPV) infection has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma (OSCC) is still unclear. Therefore, a systematic review and meta-analysis was performed to evaluate the prognostic value of HPV infection in OSCC patients.Study Design: Systematic literature review with meta-analysis.Methods: A systematic literature review was conducted in accordance with PRISMA guidelines in PubMed, EMBASE, and MEDLINE databases. The primary outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and secondary outcomes were local control (LC), regional control (RC), and distant control (DC).Results: A total of 22 articles with 3065 OSCC patients were included in this study. Meta-analysis demonstrated that compared to HPV-negative OSCC patients, HPV-positive OSCC patients had a significantly shorter OS (hazard ratio [HR]

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Human papillomavirus in carcinomas of the tongue: clinical and prognostic implications

Cited by 12 publications

References 43 publications

Integrated analysis linksTP53, NOTCH, SLC38Aand 11p with survival in patients with oral tongue squamous cell carcinoma

Integrated analysis linksTP53, NOTCH, SLC38Aand 11p with survival in patients with oral tongue squamous cell carcinoma

Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma

The Prognostic Value of Human Papilloma Virus Infection in Oral Cavity Squamous Cell Carcinoma: A Meta‐Analysis

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