A wide range of human papillomavirus (HPV) genotypes have been detected in oral mucosa. Clinical infections with low-risk genotypes manifest as squamous papilloma, condyloma acuminatum, verruca vulgaris, or multifocal epithelial hyperplasia. Clinical infections with high-risk genotypes have been associated with malignant lesions. The most common genotype isolated from subclinical infection is HPV-16. A causal role for HPV in carcinogenesis of oral squamous carcinoma is minimal. Ongoing vaccination against HPV types 6, 11, 16, and 18 is expected to decrease the spread of infection and decrease the carcinogenic potential of HPV-16 in the oropharynx and oral cavity.