Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics

  • Abdolamir AllamehEmail author
  • Abdolkarim Moazeni-Roodi
  • Iraj Harirchi
  • Mehrdad Ravanshad
  • Maziar Motiee-Langroudi
  • Ata Garajei
  • Azin Hamidavi
  • Seyed Alireza Mesbah-Namin
Original Article


The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold; p = 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.


OSCC HPV Smoking P16 promoter methylation P16 gene expression Iran 



This study was financially supported by Tarbiat Modares University and Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, I.R. Iran. (Grant# 92-02-51-23399).

Compliance with Ethical Standards

Conflict of Interest

The authors have declared that no potential conflict of interest exists.


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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Abdolamir Allameh
    • 1
    Email author
  • Abdolkarim Moazeni-Roodi
    • 1
    • 2
  • Iraj Harirchi
    • 3
  • Mehrdad Ravanshad
    • 4
  • Maziar Motiee-Langroudi
    • 3
  • Ata Garajei
    • 3
    • 5
  • Azin Hamidavi
    • 1
  • Seyed Alireza Mesbah-Namin
    • 1
  1. 1.Department of Clinical Biochemistry, Faculty of Medical SciencesTarbiat Modares UniversityTehranIslamic Republic of Iran
  2. 2.Department of Clinical BiochemistryIranshahr University of Medical SciencesIranshahrIran
  3. 3.Cancer Research Center, Cancer Institute of IranTehran University of Medical SciencesTehranIslamic Republic of Iran
  4. 4.Department of Medical Virology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIslamic Republic of Iran
  5. 5.Department of Oral and Maxillofacial Surgery, School of Dentistry and Department of Head and Neck Surgical Oncology and Reconstructive Surgery, School of MedicineTehran University of Medical SciencesTehranIran

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