High-risk types of human papillomavirus (HPV) may cause various tumors. The causative link between high-risk HPV and cervical cancer has been well elucidated. Recent studies have shown that HPV DNA is detectable in head and neck squamous cell carcinoma (HNSCC), esophageal carcinoma, as well as breast cancer. The mechanisms underlying HPV infection in HNSCC may be similar but not identical to that in cervical cancer. Understanding the mechanisms underlying HPV-associated carcinogenesis will be important for the HPV-associated tumor therapy.