The role for human papillomavirus (HPV) in head and neck tumors is not established. To evaluate the possible role of HPV in head and neck neoplasms, 22 cases of laryngeal squamous papilloma (LP), 32 cases of laryngeal squamous cell carcinoma (LSCC), 40 cases of nasal inverted papilloma (NIP), 14 cases of nasal squamous cell carcinoma (NSCC), and 40 cases of nasopharyngeal carcinoma (NPC) were evaluated for the presence of HPV DNA using the polymerase chain reaction (PCR) with two sets of primers in separate reactions: HPV-L1 consensus primers, HPV16 and HPV18 E7 primers for HPV nucleic acid detection. Restriction fragment length polymorphism of L1 PCR product was used for typing of HPV. Overall, HPV DNA was detected in 18 of 22 cases (81.8%) of LP, 3 of 32 cases (9.4%) of LSCC, 17 of 40 cases (42.5%) of NIP, 3 of 14 cases of NSCC (21.4%), and none of 40 cases of NPC. HPV6 was found more frequently in LP and HPV11 in NIP (P < 0.001). In the three HPV positive LSCCs, two cases had previous LP and were HPV6 and HPV11 positive, as were the prior papillomas. One other case was HPV18 positive. Only HPV16 was found in the NSCC patients. There was no significant difference in the index of HPV positivity between the NSCC cases associated with (16.7%) and without NIP (25.6%). Our results suggest that HPV plays a role in the development of both LP and NIP, and that similar viral types (i.e., HPV6 and HPV11) may exhibit relative differences in their tissue specificity. HPV appears to be of limited importance as a co-factor in LSCC and NPC lesions, indicating differences in the pathogenesis between papillomas and carcinomas in the upper respiratory tract.