Human papillomavirus prevalence, integration, and expression in head and neck cancers.

E.M. Smith a, KF Summersgillb, J.M. Ritchiec, J.R. Ansond, M.J. Lace d, H.T. Hoffmane, J.P. Klussmannf, H.P. Dienesg, T.H. Haugen d,h, L.P. Turek d,h

Departments of aEpidemiology, cBiostatistics, dVeterans Affairs Medical Center, eOtolaryngology, hPathology, University of Iowa, Iowa City; bDepartment of Oral Pathology, University of Pittsburgh; and Departments of Oto-Rhino-Laryngology, Head and Neck Surgery f and Pathology, University of Cologne, Germany.

AIM The objective of this study was to determine the role of HPV in association with other risk factors in 177 head and neck (H&N) cancers. METHODS Tumors were evaluated for HPV presence/type by PCR-amplification, 32P-hybridization, sequencing, and laser microdissection (LMD). HPV-16 tumors were evaluated for E6/E7 oncogene expression. Viral integration into the human genome was evaluated by examining disruption of the E2 gene and sequencing of human/viral hybrid mRNAs. RESULTS HPV was detected in 20.9% of patients. Oncogenic HPV types were in 34 tumors (19.2%): HPV-16 in 29, HPV-18 in one, and HPV-33 in four. The palatine tonsil (58.6%) was most likely to contain HPV. The oropharynx was more likely to harbor oncogenic HPV than the oral cavity (OR=6.0, 95% CI, 2.5-14.7). Poorly-differentiated squamous cell carcinoma (SCC) was more likely to contain HPV (40%) than well-differentiated/moderately-differentiated SCC (15.2%) (OR=6.5, 2.2-19.2). Tumors in clinical stage III/IV were more likely to contain HPV (25.5%) than stage 0/I/II (10.4%) (OR=4.1, 1.5-11.3). Tobacco usage was not an independent predictor of HPV risk for H&N cancer (adj. OR=0.99, 0.97-1.00). Three HPV-16 tumors demonstrated integration by disruption of the E2 DNA sequence. mRNA analysis demonstrated expression of HPV-16 E6 and E7 genes in two HPV-16 positive tumors examined. Both demonstrated viral integration into the human genome. mRNA transcripts also revealed splice junctions between viral and host sequences. LMD and other findings will be presented. CONCLUSION Infection with oncogenic HPV is frequent in oral cancers, especially the oropharynx. Viral oncogene expression and viral integration suggest an integral role for HPV in oral carcinogenesis.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 1.