The aim of this study was to investigate the role of human papillomaviruses (HPVs) and alterations of p16INK4A in different squamous cell carcinomas (SCCs) of the head and neck region by screening these carcinomas for alterations in exon 2 of p16INK4A and for HPV DNA. A total of 42 samples of different SCCs of the head and neck were collected by biopsy or surgical resection. After DNA isolation, exon 2 of p16 was amplified and sequenced. HPV DNA was detected by applying a broad-spectrum polymerase chain reaction system. Mutations were found in 4 of our 42 samples. A total of 27 biopsies showed the presence of HPV DNA. All of the biopsies showing a mutation in exon 2 of CDK4 were HPV-positive, except the first biopsy of an oropharyngeal carcinoma. It might be possible that HPV infection and mutations in the exon 2 of CDK4 play a causal role in malignant transformation in a small number of squamous carcinomas of the head and neck region.