RAS GENE-MUTATIONS AND HPV INFECTION ARE COMMON IN HUMAN LARYNGEAL CARCINOMA

To evaluate the role of ras activation and human papillomavirus (HPV) infection in laryngeal carcinoma, we analyzed tumor DNA from 43 cases, including 25 primary laryngeal tumors, 12 lymph-node and one skin metastases, and 5 recurrent laryngeal carcinomas. Thirteen normal laryngeal tissues and 7 benign laryngeal nodule biopsy specimens along with normal tissue surrounding laryngeal carcinoma in 2 cases were also included. The polymerase-chain-reaction technique was used to amplify DNA fragments containing codon 12 and 61 of H-, K- and N-ras, also HPV 16, 18 and 33 DNA, subsequently hybridized with sequence-specific oligonucleotides. DNA samples from 22 patients with laryngeal carcinoma revealed ras mutations (18 in N-ras codon 12, 6 in H-ras codon 61, and 3 in K-ras codon 61). Likewise, HPV DNA was found in 16 cases (HPV 16,18 and 33 in 3 cases, 14 cases and 1 case respectively). ras mutations were significantly higher in metastatic tumors (10 of 13 cases) than in primary (11 of 25 cases) and recurrent laryngeal carcinomas (1 of 5 cases). HPV DNA was detected in 60% of recurrent, 44% of primary and 15% of metastatic tumors. Only 2 of the 13 normal laryngeal tissues and 1 out of 7 laryngeal nodule specimens were found to contain HPV DNA. These results suggest that ras activation, especially in N-ras codon 12.1 (GGT --> AGT) and HPV infection are 2 important factors in (multistage) laryngeal carcinogenesis. The ras mutation may be associated with metastatic ability of the tumor.