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Differential survival trends for patients with tonsillar, base of tongue and tongue cancer in Sweden.

https://arctichealth.org/en/permalink/ahliterature134383
Source
Oral Oncol. 2011 Jul;47(7):636-41
Publication Type
Article
Date
Jul-2011
Author
Lalle Hammarstedt
Yunxia Lu
Linda Marklund
Tina Dalianis
Eva Munck-Wikland
Weimin Ye
Author Affiliation
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Sweden. lalle.hammarstedt@karolinska.se
Source
Oral Oncol. 2011 Jul;47(7):636-41
Date
Jul-2011
Language
English
Publication Type
Article
Keywords
Age Factors
Carcinoma, Squamous Cell - mortality - virology
Female
Humans
Male
Middle Aged
Papillomavirus Infections - mortality - virology
Prevalence
Prognosis
Risk factors
Survival Rate - trends
Sweden - epidemiology
Tongue Neoplasms - mortality - virology
Tonsillar Neoplasms - mortality - virology
Abstract
Tonsillar, base of tongue and tongue cancer have similar anatomical and histopathological appearances but present differences in prognosis. Human papillomavirus (HPV) is a known risk factor for tonsillar and base of tongue cancer, and a survival benefit has been shown for these tumors; however, HPV prevalence in tongue cancer is low. Tonsillar, base of tongue and tongue cancer patients registered in the Swedish Cancer Registry between 1960 and 2004 were followed from the date of cancer diagnosis until death, emigration out of Sweden, or the end of a follow-up (5 years since cancer diagnosis), whichever occurred first. The relative survival rate was computed as the ratio of the observed to the expected survival rate, in which the latter was inferred from the survival of the entire Swedish population in the same age, sex and calendar year stratum. The relative survival rate has improved significantly over time for patients with tonsillar and base of tongue cancer although delineated by different patterns. However, the relative survival rate in tongue cancer patients exhibited only a very modest improvement during the same time period. Contrary to the overall improved survival for patients with tonsillar and base of tongue cancer, the patients with tongue cancer show a very modest improvement in Sweden since 1960. Further studies are warranted to elucidate more effective treatment options for tongue cancer patients.
PubMed ID
21592846 View in PubMed
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Human papillomavirus and survival in patients with base of tongue cancer.

https://arctichealth.org/en/permalink/ahliterature99192
Source
Int J Cancer. 2010 Aug 19;
Publication Type
Article
Date
Aug-19-2010
Author
Per Attner
Juan Du
Anders Näsman
Lalle Hammarstedt
Torbjörn Ramqvist
Johan Lindholm
Linda Marklund
Tina Dalianis
Eva Munck-Wikland
Author Affiliation
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Source
Int J Cancer. 2010 Aug 19;
Date
Aug-19-2010
Language
English
Publication Type
Article
Abstract
The incidence of base of tongue cancer is increasing in Sweden and the proportion of human papillomavirus (HPV) positive cancer has increased in Stockholm, Sweden. Between 2006 and 2007, 84% of base of tongue cancer cases in Stockholm were HPV-positive. The objective of this study was to assess the impact of HPV status on prognosis for base of tongue cancer patients. One-hundred and nine patients were diagnosed with base of tongue cancer between 1998 and 2007 in Stockholm County and 95 paraffin-embedded diagnostic tumor biopsies were obtained and tested for HPV by PCR. Eighty-seven patients had available biopsies, were treated with intention to cure and could be included in the survival analysis. Age, sex, TNM-stage, stage, treatment and survival were recorded from patient charts. Kaplan-Meier curves were used to present survival data. In multivariable analyses, a Cox proportional hazards model was used to adjust for covariates. In total 68 (78%) tumor biopsies from the 87 included patients were HPV DNA positive. Kaplan-Meier estimates showed that the overall survival for patients with HPV-positive cancer was significantly better (p=0.0004), (log-rank test) than that of patients with HPV-negative cancer. Patients with HPV-positive tumors also had significantly better disease-free survival (p=0.0008), (log-rank test) than those with HPV-negative tumors. These results further strengthen the option to consider HPV-status when planning prospective studies on treatment for base of tongue cancer.
PubMed ID
20725995 View in PubMed
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Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden.

https://arctichealth.org/en/permalink/ahliterature272973
Source
Oral Oncol. 2015 Sep;51(9):857-61
Publication Type
Article
Date
Sep-2015
Author
Tina Dalianis
Nathalie Grün
Jana Koch
Andrea Vlastos
Nikolaos Tertipis
Cecilia Nordfors
Anders Näsman
Malin Wendt
Mircea Romanitan
Cinzia Bersani
Eva Munck-Wikland
Torbjörn Ramqvist
Source
Oral Oncol. 2015 Sep;51(9):857-61
Date
Sep-2015
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
DNA, Viral - metabolism
Female
Human papillomavirus 16 - metabolism
Humans
Hypopharyngeal Neoplasms - metabolism - mortality
Male
Middle Aged
Papillomavirus Infections - metabolism - mortality
Prognosis
Survival Analysis
Sweden - epidemiology
Abstract
Hypopharyngeal cancer is a subset of head neck squamous cell carcinoma (HNSCC) with particularly poor prognosis. Human papillomavirus (HPV) is a risk factor for some HNSCC, and its presence is of prognostic value for certain subsites. However, its influence on survival in hypopharyngeal cancer has not been thoroughly investigated. Here we examine HPV DNA and p16(INK4a) (p16) overexpression in relation to clinical outcome.
Hypopharyngeal tumour biopsies from 82 patients diagnosed 2008-2013 were examined for presence of HPV DNA by a bead-based multiplex assay and for p16 expression by immunohistochemistry, and the obtained data compared to that acquired previously from 109 patients diagnosed 2000-2007 at the same clinic. A survival analysis was then performed on 142 patients (from both studies) treated with curative intent and a 3-year follow-up time.
Of the tumour biopsies 3/82 (3.7%) were HPV16 DNA and p16 positive, while 12/82 (14.6%) were p16 positive, equivalent to that in the previous study. Overall 3-year survival was significantly more favourable for patients with HPV16 DNA and p16 positive tumours as compared to survival of the other patients (86% vs. 31%, p=0.0185). A similar but not statistically significant trend was found for disease specific survival.
HPV DNA and p16 positive hypopharyngeal cancer was rare and had not increased, but had a better clinical outcome as compared to other HPV-unrelated hypopharyngeal cancer. In addition, p16 overexpression was not a suitable surrogate marker for presence of HPV or for prediction of survival in this type of cancer.
PubMed ID
26120094 View in PubMed
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Human papillomavirus, viral load and proliferation rate in recurrent respiratory papillomatosis in response to alpha interferon treatment.

https://arctichealth.org/en/permalink/ahliterature16999
Source
J Gen Virol. 2005 Jun;86(Pt 6):1695-702
Publication Type
Article
Date
Jun-2005
Author
Michael Szeps
Liselotte Dahlgren
Leena-Maija Aaltonen
John Ohd
Lena Kanter-Lewenshon
Hanna Dahlstrand
Eva Munck-Wikland
Dan Grandér
Tina Dalianis
Author Affiliation
Department of Oncology-Pathology, CancerCenterKarolinska, R8:01, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Source
J Gen Virol. 2005 Jun;86(Pt 6):1695-702
Date
Jun-2005
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antiviral agents - therapeutic use
Biopsy
Child
Child, Preschool
Comparative Study
DNA, Viral - analysis
Female
Finland
Humans
Infant
Interferon-alpha - therapeutic use
Male
Middle Aged
Neoplasm Recurrence, Local - drug therapy - virology
Papillomavirus Infections - drug therapy - virology
Papillomavirus, Human - genetics - isolation & purification
Research Support, Non-U.S. Gov't
Respiratory Tract Neoplasms - drug therapy - virology
Retrospective Studies
Sweden
Viral Load
Abstract
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.
PubMed ID
15914847 View in PubMed
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Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome.

https://arctichealth.org/en/permalink/ahliterature17586
Source
Anticancer Res. 2004 May-Jun;24(3b):1829-35
Publication Type
Article
Author
Hanna Dahlstrand
Liselotte Dahlgren
David Lindquist
Eva Munck-Wikland
Tina Dalianis
Author Affiliation
Department of Oncology-Pathology, Karolinska Institutet, Karolinska Hospital, 171 76 Stockholm, Sweden.
Source
Anticancer Res. 2004 May-Jun;24(3b):1829-35
Language
English
Publication Type
Article
Keywords
Humans
Papillomavirus Infections - complications - genetics
Papillomavirus, Human
Prognosis
Research Support, Non-U.S. Gov't
Tonsillar Neoplasms - genetics - virology
Abstract
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.
PubMed ID
15274363 View in PubMed
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Prevalence of human papillomavirus and survival in oropharyngeal cancer other than tonsil or base of tongue cancer.

https://arctichealth.org/en/permalink/ahliterature116993
Source
Cancer Med. 2012 Aug;1(1):82-8
Publication Type
Article
Date
Aug-2012
Author
Linda Marklund
Anders Näsman
Torbjörn Ramqvist
Tina Dalianis
Eva Munck-Wikland
Lalle Hammarstedt
Author Affiliation
Department of Clinical Science, Intervention and Technology, Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Karolinska Institutet Stockholm, Sweden. linda.marklund@karolinska.se
Source
Cancer Med. 2012 Aug;1(1):82-8
Date
Aug-2012
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Carcinoma, Squamous Cell - epidemiology - mortality - virology
Cyclin-Dependent Kinase Inhibitor p16 - genetics - metabolism
Female
Humans
Male
Middle Aged
Oropharyngeal Neoplasms - epidemiology - mortality - virology
Papillomavirus Infections - epidemiology - virology
Prevalence
Prognosis
Sweden - epidemiology
Tongue Neoplasms - virology
Tonsillar Neoplasms - virology
Abstract
Today, most oropharyngeal squamous cell carcinoma (OSCC) is human papillomavirus (HPV) positive and HPV alone or in combination with p16 is reported to be a favorable prognostic factor for OSCC. Patients with tumors at other OSCC sites (OOSCC) are often included in the same treatment and study protocols as patients with tonsillar- and base of tongue SCC, even though the prevalence and clinical significance of HPV infection in OOSCC is unknown. Since tonsillar and base of tongue SSC cover roughly 90% of all OSCC, there is an obvious risk that there may be a misinterpretation of the results for OOSCC. Herein, we therefore study the prevalence of HPV and p16 and their impact on survival in OOSCC. A total of 69 patients were included in the study, and 61 were included in the survival analysis. HPV and p16 were present in only 17% (12/69) and 25% (17/69) of the OOSCC cases, respectively, while the majority 69% (48/69) was both HPV and p16 negative. Neither HPV nor p16 had predictive value for clinical outcome in OOSCC in this study. In conclusion, the prevalence of HPV and/or p16 is much lower in OOSCC compared to earlier reports including all OSCC, or tonsillar- and base of tongue cancer alone and HPV and p16 had no impact on clinical outcome in OSCC in this study. Our data highlight the diversity of head neck cancer sub-sites and the importance of taking OSCC sub-sites in consideration in future clinical trials and treatment.
Notes
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PubMed ID
23342257 View in PubMed
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Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment.

https://arctichealth.org/en/permalink/ahliterature130058
Source
Int J Cancer. 2012 Sep 1;131(5):1124-30
Publication Type
Article
Date
Sep-1-2012
Author
Per Attner
Anders Näsman
Juan Du
Lalle Hammarstedt
Torbjörn Ramqvist
Johan Lindholm
Eva Munck-Wikland
Tina Dalianis
Linda Marklund
Author Affiliation
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden. per.attner@karolinska.se
Source
Int J Cancer. 2012 Sep 1;131(5):1124-30
Date
Sep-1-2012
Language
English
Publication Type
Article
Keywords
Carcinoma, Squamous Cell - mortality - therapy - virology
Chemoradiotherapy
DNA, Viral - genetics
Female
Humans
Incidence
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Papillomaviridae - genetics - isolation & purification
Papillomavirus Infections - epidemiology - mortality - virology
Polymerase Chain Reaction
Prognosis
Radiotherapy
Survival Rate
Sweden - epidemiology
Tonsillar Neoplasms - mortality - therapy - virology
Abstract
The incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and the former group could hypothetically benefit from reduced, less-toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease-specific survival after different oncological treatments in 153 patients with HPV DNA- and P16-positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease-free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV-positive tonsillar cancer treated with conventional- or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy).
Notes
Erratum In: Int J Cancer. 2012 Nov 1;131(9):E1183
PubMed ID
22038860 View in PubMed
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Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer.

https://arctichealth.org/en/permalink/ahliterature123418
Source
PLoS One. 2012;7(6):e38711
Publication Type
Article
Date
2012
Author
Anders Näsman
Mircea Romanitan
Cecilia Nordfors
Nathalie Grün
Hemming Johansson
Lalle Hammarstedt
Linda Marklund
Eva Munck-Wikland
Tina Dalianis
Torbjörn Ramqvist
Author Affiliation
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Source
PLoS One. 2012;7(6):e38711
Date
2012
Language
English
Publication Type
Article
Keywords
Alphapapillomavirus - metabolism
CD8-Positive T-Lymphocytes - immunology
Carcinoma, Squamous Cell - immunology - radiotherapy - virology
Female
Forkhead Transcription Factors - immunology
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Linear Models
Male
Middle Aged
Proportional Hazards Models
Sweden
Tonsillar Neoplasms - immunology - radiotherapy - virology
Treatment Outcome
Abstract
Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV(+)) TSCC have a better clinical outcome than those with HPV negative (HPV(-)) TSCC. However, since not all patients with HPV(+) TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome.
Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8(+)) and regulatory (Foxp3(+)) T-cells.
A high CD8(+) T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV(+) and HPV(-) TSCC patients. Similarly, a high CD8(+)/Foxp3(+) TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV(+) TSCC had in comparison to HPV(-) TSCC, higher numbers of infiltrating CD8(+) and Foxp3(+) T-cells.
In conclusion, a positive correlation between a high number of infiltrating CD8(+) cells and clinical outcome indicates that CD8(+) cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8(+)/Foxp3(+)cell ratio can potentially be used for the same purpose.
Notes
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PubMed ID
22701698 View in PubMed
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9 records – page 1 of 1.