Studies on the presence and influence of human papillomavirus (HPV) in head and neck tumors

Abstract: The aim of this thesis was to confirm the presence of human papillomavirus (HPV) in tonsillar cancer and the previous finding that presence of HPV in tonsillar cancer is prognostic favorable for patient survival. Furthermore, the physical state and viral load of HPV in tonsillar cancer, and the influence of HPV on chromosomal patterns and on the clinical outcome for tonsillar cancer patients were examined. In addition, the presence of HPV in tongue cancer and influence of HPV on clinical outcome for tongue cancer patients were studied. Finally, the presence of HPV, viral load and proliferation rate were determined in recurrent respiratory papillomatosis in response to Interferon-alpha treatment. It was shown that HPV was present in 62.2% of examined tonsillar cancer and HPV was shown to be a favorable prognostic factor. Furthermore, the viral genome was shown to be mainly episomal, hence integration of the viral genome was not a requisite for malignant transformation. Quantification of I-IPV16 was performed by real-time quantitative PCR. The viral load was shown to vary greatly and patients with a higher viral load in their tumors had a significantly better disease specific survival than patients with a lower viral load. The pattern of chromosomal aberrations in tonsillar cancer was examined by comparative genomic hybridization. Generally, more aberrations were seen in HPV negative tumors compared to HPV positive tumors. In addition, there were specific differences between HPV positive and HPV negative tonsillar cancers. Gain of chromosome 3q was statistically more common in the HPV positive versus negative tonsillar tumors, while gain of chromosome 7 was more common in HPV negative tumors. Survival could not be correlated to gain or loss of any specific chromosome since there were too few cases in each group, however, HPV was a prognostic favorable factor. HPV was found in 40% of examined base of tongue cancer patients and patients with HPV positive tumors had a significantly better disease specific survival compared to patients with HPV negative tumors. In contrast, only 2.4% of examined mobile tongue cancer patients were HPV positive and hence presence of HPV could not be correlated to prognosis. Finally, the presence of HPV, viral load and proliferation rate were determined in recurrent respiratory papiflomatosis (RRP) in response to Interferon-alpha (IFN-alpha) treatment. The majority of the patients that were subjected to IFN-alpha therapy responded to the treatment. The rate of proliferation was generally high, and remained unchanged during IFN-alpha treatment. The vital load varied between the biopsies and both patients with a low, as well as a high, viral load responded to IFNalpha treatment, indicating that the viral load is not a determinant for responsiveness.