Objectives Papilloma is a common benign epithelial tumor of the respiratory tract in adults. Its histological structure and immune environment vary from site to site. This study investigated the disease characteristics and prognostic differences of papillomas at various primary locations. Methods Clinical data was collected from patients with adult glossal root and hypopharyngeal papilloma admitted to our tertiary referral center between January 2010 and December 2020, and compared with patients with laryngeal papilloma. Differences in age, sex, smoking, alcohol consumption, single or multiple lesions, surgical methods, immunohistochemical indexes, Ki-67 and p16, were analyzed in patients with different primary papilloma sites. Results A total of 84 cases of glossal root papilloma, 51 cases of hypopharyngeal papilloma, and 51 cases of laryngeal papilloma were included. Differential analysis between groups showed that there were statistically significant differences in age, sex, smoking, single and multiple lesions, and surgical methods in the different primary sites. Ki-67 expression in laryngeal papilloma was higher than that in glossal root and hypopharyngeal papilloma. There was no significant difference in p16 expression in the three groups. In terms of prognosis, laryngeal papilloma is more likely to relapse than glossal root or hypopharyngeal papilloma, and the recurrence time is shorter. Conclusions As the largest clinical study of papilloma in different primary locations, this study found that the clinical characteristics and postoperative recurrence of papilloma of the glossal root and hypopharynx differ from those of papilloma of the larynx. This finding supports the current clinical experience in treating papillomas in different locations and facilitates the development of clinical treatment plans.