Purpose <p>We previously identified examination time and 2-year interval as effective quality indicators for detecting upper gastrointestinal cancer during screening esophagogastroduodenoscopy (EGD). We evaluated the significance of biennial endoscopy in detecting pharyngeal and esophageal cancer.</p> Methods <p>Individuals who underwent multiple EGD examinations as health checkups at our center between August 2012 and January 2022 were included. Endoscopists were categorized into two groups based on their mean examination time for normal EGD findings, using a threshold of 5&#xa0;min. The associations between cancer detection rate and these indicators were analyzed using multivariable analyses.</p> Results <p>Twelve endoscopists performed more than 1000 examinations each, for a total of 28,842 examinations, detecting all (6 pharyngeal and 26 esophageal) cancers. Intervals between endoscopies were classified into three groups: ≤ 1&#xa0;year (Group 1), 1 to ≤ 2&#xa0;years (Group 2), and &gt; 2&#xa0;years (Group 3). This cancer detection rate did not differ significantly between Groups 1 and 2 (<i>p</i> = 0.761) but was significantly higher in Group 3 than in Group 2 (OR = 4.356, 95% CI = 1.161–16.333, <i>p</i> = 0.029). When Groups 1 and 2 were combined (≤ 2&#xa0;years) and compared with Group 3, an interval of &gt; 2&#xa0;years was significantly associated with a higher detection rate, including cases not curable by endoscopic resection (OR, 4.710; 95% CI, 1.806–12.282; <i>p</i> = 0.002). Examination time was not associated with the cancer detection rate (<i>p</i> = 0.944).</p> Conclusions <p>These findings support the significance of biennial endoscopy in detecting pharyngeal and esophageal cancer as well.</p>