Background: Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. Methods: The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. Results: Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. Conclusions: It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. Practical Implications: Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry.