The human papillomavirus (HPV) is involved in the development of different benign and malignant lesions that include in particular squamous tumours of the cervix, skin and the respiratory tracts. In particular, the ‘high risk’ HPV type 16 (HPV 16) causes genito-rectal epithelial cancers and is suspected of causing epithelial cancers of the head and neck. To determine the presence and genotypes of HPV was determined in saliva samples from 164 subjects recruited from the Department of Surgery and Odontostomatological Sciences (University of Cagliari). For this study a sensitive seminested polymerase chain reaction (PCR) method was used to detect HPV-DNA; moreover in all positive samples, HPV genotyping was based on sequencing of the HPV genome L1 region. The results obtained with these patients (who were ethnically homogeneous), showed an interesting percentage of positive samples for HPV-DNA (30 samples out of 164–18.3%). Only two HPV genotypes have been identified in these patients, HPV 16 and HPV 31 with 76.7% and 23.3% of the positive specimens, respectively, both correlating with high carcinogenic risk. This preliminary result leads us to reflect on the presence of HPV in saliva, in particular in young asymptomatic subjects (15.38%), and its prognostic value for the possible incidence in Sardinia of oral carcinoma.