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The purpose of this study was to determine prospectively both human papillomavirus (HPV) load and physical status in different types of head and neck squamous cell carcinoma (HNSCC).HPV DNA,E6/E7mRNA expression, viral load, and physical status of 184 patients with HNSCC were examined simultaneously by polymerase chain reaction (PCR)-based methods.The HPV genome was detected in 54 HNSCC samples (29.3%), particularly in tonsillar carcinomas (69.6%). Compared with nonoropharyngeal HNSCC, oropharyngeal carcinoma harbored a relatively higher viral load, especially in tonsillar carcinoma. Although integrated or mixed status was observed in 75.6% of HPV-16–positive samples,E6/E7mRNA transcripts were detected in only 27.5% of HPV DNA-positive cases. High HPV-16 load correlated significantly withE6/E7mRNA expression.E6/E7mRNA expression in patients with HNSCC with low viral load remains low even in cases of integration to the host genome. Tonsillar carcinomas were significantly associated with HPV among various types of HNSCC.