Multiple cancers frequently occur in the upper aerodigestive tract. The high incidence rate of multiple carcinomas in this region is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus (S. anginosus) is associated with esophageal, gastric, and pharyngeal cancer tissues. In this study, a highly specific quantification method for S. anginosus DNA using real-time PCR was established. We employed this assay to determine whether S. anginosus is also associated with oral cancer tissues. This precise quantification method revealed different degrees of infection with S. anginosus in esophageal cancer and oral cancer. We assayed 10 ng of genomic DNA from cancer tissues, and found that eight of 18 samples (44%) from the esophagus contained a detectable level ( > > > >10 fg) of S. anginosus DNA, whereas this was the case for only five of 38 samples (13%) of oral cancer. The quantity of S. anginosus DNA in the esophageal cancer tissues was significantly higher than in oral cancer. The maximum amount of S. anginosus DNA was approximately ten times higher in esophageal than in oral cancer tissues. In addition, none of the five different oral cancer sites (floor of the mouth, mandibular gingival, maxillary gingival, buccal mucosal, and tongue) showed significant signs of S. anginosus infection. On the other hand, most non-cancerous tissues of the esophagus and tongue showed an undetectable level of S. anginosus. These results suggest that S. anginosus is associated with esophageal cancer, but is not closely related with oral cancer. (Cancer Sci 2003; 94: 492-496) acterial and viral infections are important factors in cancer development.1) It has been reported that Helicobacter pylori (H. pylori) is associated with gastritis, gastric atrophy, and gastric cancer.2-4) The presence of microorganisms in several kinds of human cancers was recently investigated, and Streptococcus anginosus (S. anginosus) DNA fragments were frequently found in DNA samples from esophageal cancer tissues, gastric cancer tissues, and dysplasia of the esophagus.5, 6) Viable S. anginosus was also recovered from esophageal cancer tissues (unpublished data). These results suggest that S. anginosus infection occurs at an early stage of esophageal cancer and is related to esophageal and gastric carcinogenesis. S. anginosus is classified as an oral bacterium and can be isolated from several parts of the body such as the oral cavity, gastrointestinal tract, and genitourinary tract. It is often associated with pyogenic infections, including endocarditis. 7-9) S. anginosus DNA has also been found in head and neck squamous cell carcinomas 10) ; it was found much less frequently in non-cancerous tissues of the esophagus and was absent from the colon, lung, bladder, renal, and cervical cancer tissues. 6) Therefore, it was suggested that S. anginosus DNA is associated with cancers in the upper digestive tract, although the involvement of S. anginosus infection in the carc...