Human papillomaviruses (HPV) are commonly found in benign neoplasms of a wide range of epithelial surfaces. Different HPV genotypes are associated with benign lesions, including common warts, anogenital warts, conjunctival squamous cell papillomas and laryngeal papillomas. HPVs are presented as putative etiological agents of various benign oral squamous cell lesions, including squamous cell papillomas, with HPV prevalence ranging from 0 to 100% in previous studies. The aim of the present study was to investigate the potential etiological role of HPV in oral papillomas, by determining the prevalence of HPV infections in a collection of 343 archival tissue specimens. The presence of HPV infection was determined in 58/343 (16.9%) tissue samples, using GP5+/6+/68 polymerase chain reaction (PCR) and Gamma-HPV PCR in combination with Sanger sequencing, HPV-204 real-time PCR (RT-PCR) and HPV-1/-63 RT-PCR. In our collection of samples, the most frequently detected HPV was HPV-6 (34/58; 58.6%), followed by HPV-1, -2, -10, -11, -13, -16, -27, -32, -44 (Subtype HPV-55) and -74 in sporadic cases of oral squamous cell papillomas. The combination of different HPV detection methods used, in situ hybridization results and viral load estimations, obtained in the present study, suggest that HPV-6 could be etiologically associated with the development of approximately 10% of oral squamous cell papillomas. Furthermore, the results suggest that oral squamous cell papillomas can be caused by HPV-11 or HPV-44 (Subtype HPV-55) infection in less than 1% of cases.