The DNAs of human papillomavirus (HPV) types 4, 16 and 18 have been detected in biopsies of normal and malignant human oral mucosa by Southern blot hybridization and the polymerase chain reaction (PCR). By the former technique, HPV-4, HPV-16 and HPV-18 DNAs were detected in three separate carcinomas but were found in adjacent dysplastic and normal tissue by the PCR only. The PCR technique also allowed detection of HPV-16 and HPV-18 DNA in additional carcinomas and normal samples. The oral HPV-4 DNA was molecularly cloned and extensive restriction analysis and nucleotide sequencing showed identity with the prototype HPV-4 DNA. The HPV-18 DNA detected by Southern blot hybridization showed an altered restriction pattern in the E1 region of the viral genome; however direct nucleotide sequencing of PCR products from the E6 open reading frame showed no sequence alterations in either normal or malignant samples.


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