Biological evidence that human papillomaviruses are etiologically involvedin a subgroup of head and neck squamous cell carcinomas

High-risk human papillomaviruses (HPVs) have been proposed to be associated with a subset of head and neck cancers (HNSCCs), However, clear biological evidence linking HPV-mediated oncogenesis to the development of HNSCC is h ardly available. An important biological mechanism underlying HPV-mediated carcinogenesis is the inactivation of p53 by the HPV E6 oncoprotein. In the present study we investigated this biological relationship between HPV and HNSCC, In total 84 HNSCC tumors were analyzed for the presence of high-ris k HPV nucleic acids by DNA polymerase chain reaction-enzyme immunoassay (PC R-EIA) and E6 reverse transcriptase (RT)-PCR as well as for the presence of mutations in the p53 gene. We found 20/84 HPV16 DNA-positive cases with on e or more DNA assays, 10 of which were consistently positive with all assay s. Only 9/20 cases showed E6 mRNA expression, indicative for viral activity . Only these nine E6 mRNA-positive cases all lacked a p53 mutation, whereas both the other HPV DNA-positive and HPV-DNA negative tumors showed p53 mut ations in 36% and 63% of the cases, respectively. Moreover, only in lymph n ode metastases of HPV E6 mRNA-positive tumors both viral DNA and E6 mRNA we re present. Our study provides strong biological evidence for a plausible e tiological role of high-risk HPV in a subgroup of HNSCC, Analysis of E6 mRN A expression by RT-PCR or alternatively, semiquantitative analyses of the v iral load, seem more reliable assays to assess HPV involvement in HNSCC tha n the very sensitive DNA PCR analyses used routinely. (C) 2001 Wiley-Liss, Inc.