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The aim of this study was to identify recurrent respiratory papillomatosis patients who may benefit from interferon (IFN)-alpha treatment and to determine the means of IFN-alpha action. The presence of human papillomavirus (HPV) and viral load and proliferation rate in pre-, ongoing and post-treatment respiratory papillomatosis biopsies were examined retrospectively in 25 patients, 18 of whom were IFN-alpha treated and seven of whom were IFN-alpha non-treated. Using PCR, HPV was found to be present in 20/25 respiratory papillomatosis patients and HPV type was determined for 18/25 patients (12 HPV6 and six HPV11). Eighteen of the patients were treated with IFN-alpha, 14 of whom were HPV positive (eight HPV6, five HPV11 and one undefined HPV). Response to IFN-alpha therapy was observed in 12 patients (7/8 HPV6, 3/5 HPV11, 1/1 undefined HPV and 1/4 HPV negative), while six patients (1/8 HPV6, 2/5 HPV11 and 3/4 HPV negative) did not respond to therapy. Viral load, determined by quantitative real-time PCR (between 0.03 and 533 HPV copies per cell), and proliferation rate, determined as the percentage of Ki-67-positive cells (between 8 and 54 %), were similar in IFN-alpha-treated and non-treated patients and were generally unaffected by IFN-alpha treatment. In summary, most (12/18) IFN-alpha-treated patients responded to therapy. Moreover, there was a tendency for patients with HPV6-positive (7/8) respiratory papillomatosis to respond more frequently to IFN-alpha therapy than patients with HPV11 (3/5) or HPV-negative (1/4) respiratory papillomatosis. Finally, the presence of HPV and viral load and proliferation in respiratory papillomatosis biopsies was similar in patients treated or not with IFN-alpha and were in general unaffected by IFN-alpha treatment.

Human papillomavirus (HPV) has been associated with some types of human cancer. The aim of this study was to investigate if HPV could be associated with human primary malignant melanoma in non sun-exposed body areas like mucous membranes. Through the Swedish National Cancer Registry, in compliance with the rules of the Human Ethical Committee, histopathological specimens were collected from different pathological laboratories throughout Sweden. The histopathological diagnosis was reviewed, and from 45 primary melanomas, tumour tissue was micro-dissected and analysed further. A protocol for detection of HPV DNA using general HPV primers GP5 + /GP6+ or CPI/IIG, which together identify 36 different HPV subtypes, was developed. This protocol could detect presence of HPV DNA in less than 10 ng of DNA of a control cell that contained 1-2 copies of HPV type 16/cell. Before HPV testing the melanoma samples were examined for amplifiable DNA by a beta-microglobulin PCR and 39 were positive. Thirty-five of these could be evaluated for HPV DNA and no samples were positive according to all five defined criteria for HPV positivity although two were positive according to 4/5 criteria. In conclusion, HPV is rarely detected in primary malignant melanomas of non-sun exposed body areas.

The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer. The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GP5+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%). The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients. In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, and has a positive impact on disease-specific survival in patients with base of tongue cancer., ((c) 2004 Wiley-Liss, Inc.)

The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data demonstrate that approximately half of all tonsillar cancer is HPV positive. Moreover, patients with HPV positive cancer have a less risk of relapse and have a longer survival compared to patients with HPV negative tonsillar cancer. The longer survival is not dependent on that HPV positive tonsillar cancer is more sensitive to radiation therapy. However, in general HPV positive cancer exhibits less genetic instability in that it has a lesser degree of aneuploidy and fewer chromosomal aberrations when compared to HPV negative tonsillar cancer.

The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data in scientific reports and data from the Karolinska Hospital and Karolinska Institute, Sweden, demonstrate that approximately half of all tonsillar cancer is HPV-positive. Moreover, patients with HPV-positive cancer have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. The favourable outcome for patients harbouring HPV-positive tonsillar cancer cannot be attributed to increased radiosensitivity, since there is no significant difference in sensitivity to radiotherapy between HPV-positive and -negative tonsillar cancer. However, HPV-positive cancer exhibits less genetic instability i.e. shows a lower degree of aneuploidy and a tendency to have fewer chromosomal aberrations, when compared to HPV-negative tonsillar cancer.

Our aim was to map and compare genomic imbalances in human papillomavirus (HPV)-positive and -negative squamous cell carcinomas of the tonsil. Twenty-five primary carcinomas were analyzed by comparative genomic hybridization. Fifteen (60%) were found to be HPV-positive by PCR, and the majority were HPV-16. There were statistically significant differences in the distribution of DNA gains and losses between the HPV-positive and -negative samples. Eleven of 15 HPV-positive samples (73%) showed gain on chromosome 3q24-qter, while only 4/10 (40%) HPV-negative samples had the same gain (p = 0.049). Furthermore, 4/10 (40%) HPV-negative samples but no HPV-positive samples had gain on chromosome 7q11.2-q22 (p = 0.017). As expected, and similar to previous studies, patients with an HPV-positive tumor had a statistically significantly better disease-specific survival than patients with an HPV-negative tumor (p = 0.002). The most common changes, e.g., gain on 3q or 8q, loss on 11q or 13 and loss on chromosome 7q in HPV-negative tumors, did not have any influence on prognosis. However the number of cases in each subgroup was limited., (Copyright 2003 Wiley-Liss, Inc.)

The aim of our study was to investigate the physical state and the viral load of HPV-16 in tonsillar cancer and to correlate these findings with clinical outcome. To distinguish between integrated and episomal forms of HPV, 22 fresh-frozen tonsillar cancer samples were analysed by a method based on restriction enzyme cleavage, ligation and PCR (rliPCR). HPV-16 was detected in 11/22 and HPV-33 in 1/22 of the cancers, hence 12/22 (55%) of the tumours were HPV positive. Only extrachromosomal forms of HPV-16 were observed. Full-length episomal HPV was detected exclusively in 7/11 of the cancers, whereas both full-length and deleted forms of episomal HPV-16 were found in parallel in 2 other tumours. In 1 tumour only a deleted episomal form of HPV-16 was present. In the remaining HPV-16 positive tumour both full-length episomal as well as an 11 kbp PCR product were detected and if the 11 kbp product contained integrated HPV, or was off-size linearised episomal could not be determined. In 2 cervical cancer controls, HPV-16 was integrated and could be chromosome located. HPV-16 was quantified by real-time PCR and most tonsillar cancers contained between 10 to a few hundred copies of HPV per beta-actin. The 6 patients with tumour sections with > or =190 HPV-16 copies/beta-actin remained tumour free (p = 0.026) and had a better survival rate (p = 0.039) when compared to the 5 patients with tumours sections with < or =60 HPV-16 copies/beta-actin. In conclusion, HPV-16 is mainly episomal in tonsillar cancer. The viral load showed a wide distribution and the clinical outcome in our study was better when the HPV load was higher., (Copyright 2002 Wiley-Liss, Inc.)