| 1. |
- Bersani, Cinzia, et al.
(författare)
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MicroRNA-155,-185 and-193b as biomarkers in human papillomavirus positive and negative tonsillar and base of tongue squamous cell carcinoma
- 2018
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Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 82, s. 8-16
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Three-year disease-free survival (DFS) is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue cancer (TSCC/BOTSCC) treated with radiotherapy alone, and today's intensified therapy does not improve prognosis. More markers are therefore needed to more accurately identify patients with good prognosis or in need of alternative therapy. Here, microRNAs (miRs) 155, 185 and 193b were examined as potential prognostic markers in TSCC/BOTSCC.Material and methods: 168 TSCC/BOTSCC patients diagnosed 2000-2013, with known data on HPV-status, CD8(+) tumour infiltrating lymphocytes, tumour staging and survival were examined for expression of miR-155, -185 and -193b using Real-Time PCR. Associations between miR expression and patient and tumour characteristics were analysed using univariate testing and multivariate regression.Results: Tumours compared to normal tonsils showed decreased miR-155 and increased miR-193b expression. miR-155 expression was associated with HPV-positivity, low T-stage, high CD8(+) TIL counts and improved survival. miR-185 expression was associated with HPV-negativity and a tendency towards decreased survival, while miR-193b expression was associated with higher T-stage, male gender and lower CD8(+) TIL counts, but not with outcome. Upon Cox regression, miR-185 was the only miR significantly associated with survival. Combining miR-155 and miR-185 to predict outcome in HPV+ patients yielded an area under curve (AUC) of 71%.Conclusion: Increased miR-155 expression was found as a positive predictor of survival, with the effect mainly due to its association with high CD8(+) TIL numbers, while miR-185 independently associated with decreased survival. Addition of these miRs to previously validated prognostic biomarkers could improve patient stratification accuracy.
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| 2. |
- Dahlstrand, Hanna, et al.
(författare)
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Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer.
- 2008
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1133-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this review is to present the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. An increase in the incidence of tonsillar cancer has been reported and recent data suggest that this increase is due to an increased proportion of HPV in these tumours. Furthermore, patients with HPV positive cancer have been shown to have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. Tailoring individual treatment in tonsillar cancer may be of importance in order to reduce patient suffering as well as to increase patient survival. Finally, the fact that the presence of HPV-type 16 E6 and E7 mRNA has been ascertained in tonsillar cancer suggests that HPV-16 indeed is an aetiological factor associated with the disease and that preventive vaccination for this patient group should be discussed.
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| 3. |
- Du, Juan, et al.
(författare)
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Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden
- 2012
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:9, s. 1468-1471
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.
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| 4. |
- Lindquist, David, et al.
(författare)
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Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7.
- 2007
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Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 1:3, s. 350-5
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Tidskriftsartikel (refereegranskat)abstract
- From 1970 to 2002 in the Stockholm area, we revealed a parallel three-fold increase in the incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases, indicating a possible role of HPV infection in this disease. We have now examined whether HPV and viral load in pre-treatment tonsillar cancer biopsies correlates to disease prognosis, and whether the presence of HPV-16 E6 and E7 mRNA could be ascertained. The presence of HPV-16, but not viral load, in tonsillar cancer was shown to be a favourable prognostic factor for clinical outcome. Moreover, E6 and/or E7 were expressed in almost all assessable HPV-16 positive cases, supporting an oncogenic role of HPV-16 in tonsillar cancer.
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| 5. |
- Näsman, Anders, et al.
(författare)
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Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden : an epidemic of viral-induced carcinoma?
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 362-6
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Tidskriftsartikel (refereegranskat)abstract
- In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.
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| 6. |
- Romanitan, Mircea
(författare)
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Studies on human papillomaviruses in head and neck cancer
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The traditional risk factors for HNSCC are smoking and alcohol. However, recently IARC has also recognized human papillomaviruses (HPV) as an etiological factor for oropharyngeal cancer, a subset of head and neck cancers. Among oropharyngeal cancer, tonsillar and tongue base cancer dominate, both often associated with HPV. The aim of the present study was to examine the involvement of human papillomavirus (HPV) in two subtypes of HNSCC, tonsillar and hypopharyngeal cancer. For tonsillar cancer the purpose was to evaluate the prevalence of HPV over time and in relation to clinical outcome. In addition we wanted to evaluate if EGFR or phosphorylated EGFR were useful as markers, together with HPV, to predict response to treatment. For hypopharyngeal cancer, the aim was to analyze the prevalence of HPV and if HPV was a risk factor for this tumor type. In the first paper, we found a 7‐fold increase in the incidence of HPV positive tonsillar cancer, between 1970 and 2006, in the County of Stockholm, highlighting HPV as the causative factor for the increased incidence of this tumor type. In addition we found a decline in the incidence of HPV negative tonsillar cancer. In the second paper, we found a high 5‐year disease specific survival for HPV positive tonsillar cancer (81%), as compared to 36% for patients with HPV negative tonsillar cancer. HPV E6 and/or HPV E7 RNA were present in 94% of the samples analyzed, demonstrating the involvement of HPV in carcinogenesis. In the third paper, we analyzed the presence of HPV in HNSCC from Greece and found that HPV is common in tonsillar carcinoma also from this country. In the fourth paper, the presence of HPV and overexpression of p16 in hypopharyngeal cancer from patients in Stockholm, was evaluated. Only 6% were HPV positive, indicating that HPV is not an important risk factor for this disease. In the fifth paper, overexpression of EGFR and presence of phoshorylated EGFR in tonsillar cancer, were evaluated in relation to tumor HPV status and clinical outcome. We found a correlation between the presence of phosphorylated EGFR and HPV, but not between phosphorylated EGFR and clinical outcome, when HPV positive and negative tumors were evaluated separately. Our studies revealed HPV as a major factor behind the increased incidence of tonsillar cancer in the Stockholm area and an important prognostic factor for this disease, while HPV was not an important risk factor for hypopharyngeal cancer in this area.
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