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Article ; Online: Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011.

Braakhuis, Boudewijn J M / Leemans, C René / Visser, Otto

2014 Volume 50, Issue 7, Page(s) 670–675

Abstract: Background: Incidence and survival trends of head and neck squamous cell carcinoma (HNSCC) are essential knowledge for guiding policy making and research.: Methods: The total population of the Netherlands was studied covering 1989-2011. Two-and five- ... ...

Abstract	Background: Incidence and survival trends of head and neck squamous cell carcinoma (HNSCC) are essential knowledge for guiding policy making and research. Methods: The total population of the Netherlands was studied covering 1989-2011. Two-and five-year survival and age-standardized incidence rates of HNSCC were assessed in relation to site, gender and age (15 years-of-age categories). Results: We recorded a statistically significant increase of oral, oropharyngeal and hypopharyngeal carcinoma for males and females of all ages, varying from 0.6% (hypopharynx in males) to 2.7% (oropharynx in females) per year. The incidence of laryngeal carcinoma significantly decreased for males with 2.3% per year; for females the situation was stable. In young adults (below 45 years of age) the incidence figures were different: significant decreasing incidence trends were seen for both genders for carcinomas of the oropharynx, hypopharynx and larynx. Regarding oral carcinoma, no change was observed for the young patient group, but for subsites trends were divergent. Carcinoma of the floor or mouth decreased for both genders, but carcinoma of the tongue rose by a significant 2.8% per year for young males. Five-year survival trends for all ages showed no change for laryngeal carcinoma, a small improvement for oral and hypopharyngeal carcinoma, and a substantial and significant improvement of survival from 36% to 47% survival over the total period for oropharyngeal carcinoma. Conclusion: In the Netherlands for the last two decades, the incidence of oral, oropharyngeal and hypopharyngeal squamous cell carcinoma has increased and survival has improved. The incidence of laryngeal carcinoma has decreased in males, and remained unchanged in females; survival from laryngeal carcinoma has not changed.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Carcinoma, Squamous Cell/epidemiology ; Female ; Humans ; Hypopharyngeal Neoplasms/epidemiology ; Incidence ; Laryngeal Neoplasms/epidemiology ; Male ; Middle Aged ; Mouth Neoplasms/epidemiology ; Netherlands/epidemiology ; Oropharyngeal Neoplasms/epidemiology ; Sex Distribution ; Survival Rate/trends
Language	English
Publishing date	2014-04-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2014.03.008
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Electronic Cigarettes and Head and Neck Cancer Risk-Current State of Art.

Szukalska, Marta / Szyfter, Krzysztof / Florek, Ewa / Rodrigo, Juan P / Rinaldo, Alessandra / Mäkitie, Antti A / Strojan, Primož / Takes, Robert P / Suárez, Carlos / Saba, Nabil F / Braakhuis, Boudewijn J M / Ferlito, Alfio

Cancers

2020 Volume 12, Issue 11

Abstract: E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper ... ...

Abstract	E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.
Language	English
Publishing date	2020-11-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12113274
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Article ; Online: De-escalation studies in HPV-positive oropharyngeal cancer: How should we proceed?

Oral oncology

2021 Volume 123, Page(s) 105620

Abstract: Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma ( ... ...

Abstract	Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).
MeSH term(s)	Carcinoma, Squamous Cell/diagnosis ; Carcinoma, Squamous Cell/virology ; Head and Neck Neoplasms ; Humans ; Oropharyngeal Neoplasms/diagnosis ; Oropharyngeal Neoplasms/virology ; Papillomaviridae ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis ; Retrospective Studies
Language	English
Publishing date	2021-11-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2021.105620
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The molecular biology of head and neck cancer.

Leemans, C René / Braakhuis, Boudewijn J M / Brakenhoff, Ruud H

Nature reviews. Cancer

2010 Volume 11, Issue 1, Page(s) 9–22

Abstract: Head and neck squamous cell carcinomas (HNSCCs) are caused by tobacco and alcohol consumption and by infection with high-risk types of human papillomavirus (HPV). Tumours often develop within preneoplastic fields of genetically altered cells. The ... ...

Abstract	Head and neck squamous cell carcinomas (HNSCCs) are caused by tobacco and alcohol consumption and by infection with high-risk types of human papillomavirus (HPV). Tumours often develop within preneoplastic fields of genetically altered cells. The persistence of these fields after treatment presents a major challenge, because it might lead to local recurrences and second primary tumours that are responsible for a large proportion of deaths. Aberrant signalling pathways have been identified in HNSCCs and inhibition of epidermal growth factor receptor (EGFR) has proved a successful therapeutic strategy. In this Review, we discuss the recent literature on tumour heterogeneity, field cancerization, molecular pathogenesis and the underlying causative cancer genes that can be exploited for novel and personalized treatments of patients with HNSCC.
MeSH term(s)	Animals ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Humans ; Molecular Biology
Language	English
Publishing date	2010-12-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc2982
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Gene expression profiling in head and neck squamous cell carcinoma.

Braakhuis, Boudewijn J M / Brakenhoff, Ruud H / Leemans, C René

Current opinion in otolaryngology & head and neck surgery

2010 Volume 18, Issue 2, Page(s) 67–71

Abstract: Purpose of review: Micro-array expression profiling has been proposed to have predictive and prognostic value for patients with head and neck squamous cell carcinoma. A critical update of recent publications on this topic is presented.: Recent ... ...

Abstract	Purpose of review: Micro-array expression profiling has been proposed to have predictive and prognostic value for patients with head and neck squamous cell carcinoma. A critical update of recent publications on this topic is presented. Recent findings: Thus far, some potentially interesting predictive gene profiles (consisting of 4-825 genes) have been described. The studies have focused on predicting survival, the development of lymph node metastases and the occurrence of distant metastases. The overlap of genes between studies was limited, probably related to differences in platforms, tumor subtypes and analytical methods. Validation of the profiles was suboptimal. Summary: Micro-array expression profiling has no clinical benefit for the head and neck cancer patient at this moment. Clinical implementation will depend on the outcome of studies that focus on the proper validation of the proposed profiles in large uniform patient groups and on the translation of the findings into a cost-effective and easy-to-use assay for everyday practice.
MeSH term(s)	Carcinoma, Squamous Cell/genetics ; Gene Expression Profiling/methods ; Glucose Transporter Type 3/genetics ; Head and Neck Neoplasms/genetics ; Humans ; Lymph Nodes/pathology ; Oligonucleotide Array Sequence Analysis/methods ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/genetics
Chemical Substances	Glucose Transporter Type 3 ; SALL2 protein, human ; SLC2A3 protein, human ; Transcription Factors
Language	English
Publishing date	2010-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1232518-1
ISSN	1531-6998 ; 1068-9508
ISSN (online)	1531-6998
ISSN	1068-9508
DOI	10.1097/MOO.0b013e32833693ce
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Article ; Online: Molecular and health effects in the upper respiratory tract associated with tobacco smoking other than cigarettes.

Szyfter, Krzysztof / Napierala, Marta / Florek, Ewa / Braakhuis, Boudewijn J M / Takes, Robert P / Rodrigo, Juan P / Rinaldo, Alessandra / Silver, Carl E / Ferlito, Alfio

International journal of cancer

2018 Volume 144, Issue 11, Page(s) 2635–2643

Abstract: The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. ... ...

Abstract	The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.
MeSH term(s)	Head and Neck Neoplasms/epidemiology ; Head and Neck Neoplasms/etiology ; Humans ; Incidence ; Respiratory System/drug effects ; Respiratory System/pathology ; Risk Factors ; Squamous Cell Carcinoma of Head and Neck/epidemiology ; Squamous Cell Carcinoma of Head and Neck/etiology ; Tobacco Products/adverse effects ; Tobacco Smoking/adverse effects ; Tobacco Smoking/trends
Language	English
Publishing date	2018-10-04
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.31846
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 576: Show issues

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Article ; Online: Oral and oropharyngeal cancer in The Netherlands between 1989 and 2006: Increasing incidence, but not in young adults.

Braakhuis, Boudewijn J M / Visser, Otto / Leemans, C René

Oral oncology

2009 Volume 45, Issue 9, Page(s) e85–9

Abstract: To determine incidence trends of head and neck squamous cell carcinomas (HNSCC), we analyzed site-specific data collected by The Netherlands Cancer Registry by 15years-of-age categories from 1989-2006. The age-standardized annual incidence trends of all ... ...

Abstract	To determine incidence trends of head and neck squamous cell carcinomas (HNSCC), we analyzed site-specific data collected by The Netherlands Cancer Registry by 15years-of-age categories from 1989-2006. The age-standardized annual incidence trends of all sites taken together showed a significant decrease of 0.6% for males and a significant increase of 1.8% for females. The trend for oropharyngeal carcinoma was most remarkable, with a significant increase of 2.5% and 3.0% per year for males and females, respectively. The incidence of oral carcinoma also significantly increased with a more pronounced effect for females than for males (2.0% vs. 0.5% per year). As for hypopharyngeal cancer, a significant annual increase for females (2.5%) and a stable situation for males was observed. Cancer of the larynx was the only site that showed a significant decline for males (2.4% per year), whereas it remained stable for females. In young (<45years) adults incidences decreased for all sites with 0.1-4.7%. In conclusion, recent incidence trends of HNSCC in The Netherlands vary between sites with a considerable increase of oropharyngeal cancer as the most remarkable finding. The reason for the decreasing annual incidence rate at all sites observed for Dutch young adults remains to be explained.
MeSH term(s)	Adult ; Aged ; Carcinoma, Squamous Cell/epidemiology ; Female ; Head and Neck Neoplasms/epidemiology ; Humans ; Hypopharyngeal Neoplasms/epidemiology ; Incidence ; Laryngeal Neoplasms/epidemiology ; Male ; Middle Aged ; Mouth Neoplasms/epidemiology ; Netherlands/epidemiology ; Oropharyngeal Neoplasms/epidemiology ; Registries ; Sex Distribution ; Young Adult
Language	English
Publishing date	2009-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2009.03.010
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck.

de Boer, D Vicky / Martens-de Kemp, Sanne R / Buijze, Marijke / Stigter-van Walsum, Marijke / Bloemena, Elisabeth / Dietrich, Ralf / Leemans, C René / van Beusechem, Victor W / Braakhuis, Boudewijn J M / Brakenhoff, Ruud H

Oncotarget

2017 Volume 8, Issue 58, Page(s) 97928–97940

Abstract: Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently ... ...

Abstract	Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified
Language	English
Publishing date	2017-05-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.17880
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Article ; Online: Molecular analysis of surgical margins in head and neck cancer: more than a marginal issue.

Braakhuis, Boudewijn J M / Bloemena, Elisabeth / Leemans, C René / Brakenhoff, Ruud H

Oral oncology

2010 Volume 46, Issue 7, Page(s) 485–491

Abstract: The relatively modest survival of patients surgically treated for advanced HNSCC can partly be explained by the development of local relapse. It is important that surgeons are able to predict which patients are at high risk to develop local relapse, ... ...

Abstract	The relatively modest survival of patients surgically treated for advanced HNSCC can partly be explained by the development of local relapse. It is important that surgeons are able to predict which patients are at high risk to develop local relapse, since clinical management can be tailored. Local relapse after resection of a primary HNSCC is easily explained, when tumour is detected in the surgical margins and thus residual tumour is likely to remain in the patient, but the pathobiology is more complex in cases where the margins are histologically tumour-free. Molecular studies indicate that there are two different mechanisms responsible in these cases. First, small clusters of residual tumour cells that are undetectable on routine histopathological examination (known as minimal residual cancer: MRC) proliferate and this forms the basis of recurring cancer. A second cause of relapse is a remaining field of preneoplastic cells that is struck by additional genetic hits leading to invasive cancer. It is likely that within this field, that can be over 7cm in diameter, the primary carcinoma has also emerged. Despite careful histopathological examination of the surgical margins of the primary carcinoma, it is at present not reliably possible to predict which patient will develop local relapse. Herein we focus on new developments regarding the analysis of margins, causes of local relapse, and how novel molecular techniques can be of help in a more accurate risk assessment. Critical analysis of the studies that have been published thus far shows that there is a list of promising markers, based on protein expression (immuno-histochemistry) and nucleic acid analysis. Further studies should be focused on validation and assessment of the clinical utility of these markers. Margin analysis should reveal whether one is dealing with residual cancer cells that might be treated by post-operative radiotherapy or with preneoplastic fields that remained behind. For this latter entity, there is no intervention available at present, except for a more intensive surveillance.
MeSH term(s)	Biomarkers, Tumor/genetics ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/surgery ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/surgery ; Humans ; Immunohistochemistry ; Neoplasm Recurrence, Local ; Neoplasm, Residual
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2010-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2010.01.019
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Anticancer activity and mechanism of action of retinoids in oral and pharyngeal cancer.

Klaassen, Ingeborg / Braakhuis, Boudewijn J M

Oral oncology

2002 Volume 38, Issue 6, Page(s) 532–542

Abstract: Retinoids are the natural and synthetic derivatives of vitamin A. Epidemiological studies indicate that a low intake of vitamin A is associated with an increased risk of squamous cancer. In vitro studies on cancer cells show that exposure to retinoids ... ...

Abstract	Retinoids are the natural and synthetic derivatives of vitamin A. Epidemiological studies indicate that a low intake of vitamin A is associated with an increased risk of squamous cancer. In vitro studies on cancer cells show that exposure to retinoids results in the inhibition of growth, by blocking the cell cycle or by inducing apoptosis. With respect to the clinical efficacy of retinoids some positive effects have been observed in early stage oral and oropharyngeal cancer. Administration of retinoids has been shown to elicit responses in leukoplakia, a premalignant lesion of the oral mucosa that frequently develops into invasive cancer. Furthermore, it has been possible with a retinoid, 13-cis-retinoic acid, to delay or inhibit the development of second primary tumors in patients who have been curatively treated for a first primary tumor in the oral cavity or oropharynx. Recent trials, however, failed to show protective effects on the development of second primary tumors. Because of the short duration of the response, the intrinsic resistance to retinoids and the toxic side effects, the treatment with this class of compounds has not become a standard therapy. Recent studies have shed light on how preneoplastic and neoplastic cells defend themselves against the growth inhibiting action of retinoids. An increased retinoid breakdown and an inactivation of nuclear retinoid receptor appear to be the cause of acquired or intrinsic resistance. This knowledge can be used to develop novel tumor-selective strategies. This review gives an update on the role of retinoids in oral and oropharyngeal cancer and their precursor lesions. The focus will be on the anticancer activity, the mechanism of action and future directions.
MeSH term(s)	Anticarcinogenic Agents/therapeutic use ; Humans ; Leukoplakia, Oral/drug therapy ; Mouth Neoplasms/prevention & control ; Neoplasms, Second Primary/prevention & control ; Pharyngeal Neoplasms/prevention & control ; Retinoids/therapeutic use
Chemical Substances	Anticarcinogenic Agents ; Retinoids
Language	English
Publishing date	2002-08-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1120465-5
ISSN	1879-0593 ; 1368-8375 ; 0964-1955
ISSN (online)	1879-0593
ISSN	1368-8375 ; 0964-1955
DOI	10.1016/s1368-8375(01)00118-x
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