Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

Abstract

ABSTRACT. Head and neck squamous cell carcinoma (HNSCC) has become one of the most common forms of cancer worldwide. Hypermethylation-induced silencing of tumor-associated gene has been proposed as an important cofactor in cancer pathology. This paper aimed to characterize the gene methylation patterns in human papillomavirus (HPV) associated-HNSCC. TIMP3 and APC methylation status in neoplastic (N = 92) and non-neoplastic tissues (N = 92) of HNSCC as well as their association with HPV infection were investigated via methylation-specific PCR assays. Results indicated that methylation level of TIMP3 was markedly higher in HPV-positive tumors as compared with HPV-negative tumors. Both TIMP3 and APC methylation were associated with lymph node metastasis and higher clinical stage of tumors. Patients with methylation at TIMP3 or APC had worse prognoses as compared to those without these alterations. This is the first study that shows a possible linkage between HPV infection and APC methylation. Methylation patterns of tumor-related genes may contribute to different disease prognosis in HNSCC according to the HPV infection status.

Feasibility of methylated ctDNA detection in plasma samples of oropharyngeal squamous cell carcinoma patients

“…We found an association between the absence of TIMP3 methylation and patients with clinically negative lymph nodes at diagnosis. A similar association was reported for HPV‐positive head and neck 19 and gastric cancer 20 ; our group also demonstrated that TIMP3 hypermethylation in HNC tumor tissue was associated with the development of second primary tumors, 16 and TIMP3 methylation in salivary rinse as an independent prognostic factor for HNC patients 15 . Although we were not able to find an association with survival rates, probably due to the small sample size, TIMP3 methylation is undoubtedly relevant in HNC carcinogenesis.…”

Promoter DNA methylation patterns in oral, laryngeal and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement and survival

“…Previous studies have detected M TIMP3 more frequently in tumor tissue of patients with early-stage (I/II) HNSCC compared with healthy saliva samples ( 113 , 114 ) but they did not find a clinical association with cancer. A study characterizing the epigenome in HPV + patients with HNSCC showed that aberrant TIMP3 was predominant in HPV + patients ( 115 ). The authors showed that M TIMP3 was associated with positive lymph node spread, and consequently, with a poorer prognosis.…”