After approval by the Hospital Review Board, we obtained formalin-fixed, paraffin-embedded specimens from 115 patients with primary oral SCC and 66 patients with oral ED at the Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan. Diagnosis of oral SCC and ED was based on histological examination of hematoxylin and eosin-stained tissue sections. All patients received total surgical excision of the lesions at the Department of Oral and Maxillofacial Surgery or Department of Otolaryngology, National Taiwan University Hospital during the period from 1997 to 2004. Specimens were obtained from either incisional biopsies or total surgical excision of the lesions. If lymph node was diagnosed as positive for SCC, neck dissection and postoperative radiation therapy were also included in the treatment protocol. No patient had received any cancer therapy before initial biopsies. Details of the patients’ oral habits, including daily consumption of AQs, cigarettes, and alcohol as well as the duration of these habits, were also recorded in the medical chart. Twenty biopsy specimens of normal oral mucosa (NOM) were obtained from non-AQ-chewers and non-smokers during extraction of impacted permanent lower third molars after obtaining informed consent, and used as the healthy controls.