Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil

Buexm, Luisa Aguirre; Soares-Lima, Sheila Coelho; Brennan, Paul; Fernandes, Priscila Valverde; Lopes, Monique de Souza Almeida; Carvalho, Flávia Nascimento de; Santos, Izabella Costa; Dias, Luiz Fernando; Lourenço, Simone de Queiroz Chaves; Pinto, Luís Felipe Ribeiro

doi:10.1016/j.canlet.2020.02.023

Cited by 18 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we also assessed this profile in our samples, and showed higher Line1 methylation levels in HPV-positive relative to HPV-negative OPSCC, corroborating previous data [22,[26][27][28]. Although we did not observe an association between Line1 methylation levels and OS, it is important to mention that for the same population studied here, HPV was not associated with prognosis, likely due to the high frequency of smokers [7].…”

Section: Discussionsupporting

confidence: 90%

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

Camuzi¹,

Buexm²,

Lourenço

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more detailed analysis of the transposable elements (TEs) are still missing. Here we performed pyrosequencing to evaluate a 5-CpG methylation signature and Line1 methylation in an oropharyngeal squamous cell carcinoma (OPSCC) cohort. We further evaluated the methylation levels of the TEs, their correlation with gene expression and their impact on overall survival (OS) using the TCGA cohort. In our dataset, the 5-CpG signature distinguished HPV-positive and HPV-negative OPSCC with 66.67% sensitivity and 84.33% specificity. Line1 methylation levels were higher in HPV-positive cases. In the TCGA cohort, Line1, Alu and long terminal repeats (LTRs) showed hypermethylation in a frequency of 60.5%, 58.9% and 92.3%, respectively. ZNF541 and CCNL1 higher expression was observed in HPV-positive OPSCC, correlated with lower methylation levels of promoter-associated Alu and LTR, respectively, and independently associated with better OS. Based on our findings, we may conclude that a 5-CpG methylation signature can discriminate OPSCC according to HPV status with high accuracy and TEs are differentially methylated and may regulate gene expression in HPV-positive OPSCC.

show abstract

Section: Discussionsupporting

confidence: 90%

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

Camuzi¹,

Buexm²,

Lourenço

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…For OPSCC, opposite to the other tumor subsites, for which fresh-frozen NTST was collected, the non-tumor tissue consisted of FFPE tonsils from individuals going through uvulopalatopharyngoplasty for conditions not associated with cancer. Tonsils were used based on previous studies and on the high prevalence of OPSCC arising from these organs [ 45 , 46 , 47 , 48 , 49 , 50 , 51 ], but future studies on OPSCC NTST should be performed to confirm our findings.…”

Section: Discussionmentioning

confidence: 80%

“…The number of samples analyzed was limited and we were not able to evaluate the impact of etiological factors on the DNA methylation profiles identified due to the quite homogeneous characteristics of patients, mostly heavy smokers, heavy drinkers and HPV-negative. However, it is important to mention that this is the actual profile of UADT patients in general [ 51 , 54 , 94 , 95 ]. Therefore, the molecular heterogeneity within these tumor types might be even more pronounced.…”

Section: Discussionmentioning

confidence: 99%

Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption

Soares-Lima

Mehanna

Camuzi

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.

show abstract

“…However, the association of HPV with HNSCC is less well characterized. The reported incidence of HPV in HNSCC varies greatly, approximately from 0% to 70% (23‐27). This wide range of HPV detection rates might be explained by the anatomical subsite, the inherent differences in the tested HPV DNA samples (FFPE tissues, fresh or frozen biopsy samples), but also by differences in the applied HPV DNA detection methods (e.g., in situ hybridization, PCR, Real‐time PCR, microarray) (2,8,11).…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, different geographic areas could be influencing the incidence of HPV in HNSCCs. Several studies have presented a variable prevalence of HPV infection in heterogeneous population groups living in different geographical regions (1,23,25‐27).…”

Section: Discussionmentioning

confidence: 99%

Comparison of HPV detection rate in formalin‐fixed paraffin‐embedded tissues of head and neck carcinoma using two DNA extraction kits and three amplification methods

Božić

Jovanović

Šmitran

et al. 2020

European J Oral Sciences

View full text Add to dashboard Cite

show abstract

Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil

Cited by 18 publications

References 31 publications

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption

Comparison of HPV detection rate in formalin‐fixed paraffin‐embedded tissues of head and neck carcinoma using two DNA extraction kits and three amplification methods

Contact Info

Product

Resources

About