Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal linings of the upper aerodigestive tract and are unexpectedly heterogeneous in nature. Classical risk factors are smoking and ...excessive alcohol consumption, and in recent years, the role of human papillomavirus (HPV) has emerged, particularly in oropharyngeal tumours. HPV-induced oropharyngeal tumours are considered a separate disease entity, which recently has manifested in an adapted prognostic staging system while the results of de-intensified treatment trials are awaited. Carcinogenesis caused by HPV in the mucosal linings of the upper aerodigestive tract remains an enigma, but with some recent observations, a model can be proposed. In 2015, The Cancer Genome Atlas (TCGA) consortium published a comprehensive molecular catalogue on HNSCC. Frequent mutations of novel druggable oncogenes were not demonstrated, but the existence of a subgroup of genetically distinct HPV-negative head and neck tumours with favourable prognoses was confirmed. Tumours can be further subclassified based on genomic profiling. However, the amount of molecular data is currently overwhelming and requires detailed biological interpretation. It also became apparent that HNSCC is a disease characterized by frequent mutations that create neoantigens, indicating that immunotherapies might be effective. In 2016, the first results of immunotherapy trials with immune checkpoint inhibitors were published, and these may be considered as a paradigm shift in head and neck oncology.
The molecular biology of head and neck cancer Leemans, C. René; Braakhuis, Boudewijn J. M; Brakenhoff, Ruud H
Nature reviews. Cancer,
01/2011, Letnik:
11, Številka:
1
Journal Article
Recenzirano
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.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
3.
Head and neck squamous cell carcinoma Johnson, Daniel E; Burtness, Barbara; Leemans, C René ...
Nature reviews. Disease primers,
11/2020, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and ...larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.
Summary Background Adenoid cystic carcinoma is a rare salivary gland malignancy with a poor disease free survival due to frequent distant metastases and late local recurrences. Previous single-center ...reports on outcome mostly encompass small series. In this report a relative large series of 105 cases is analyzed, all treated at the VU University Medical Center, Amsterdam, The Netherlands over a 30-year period in which treatment strategies remained unchanged. Methods All cases of ACC of the head and neck between 1979 and 2009 at our institution were analyzed through a medical chart review. Recurrence patterns and possible prognostic factors (T-stage, N-status, age, gender, type of salivary gland involved, histological grade, surgical margins, perineural invasion (PNI) and postoperative radiotherapy (RT)) were analyzed. Results One-hundred and five cases of ACC of the head and neck were identified. Five-, ten- and twenty-year survival rates for overall survival were 68%, 52% and 28%, respectively. T-stage, N-status, surgical margins, histological subtype and age were highly significant predictors for survival. PNI was not a negative prognosticator. Conclusions T-stage, N-status, surgical margins, histological grade and age are the main predictors of survival-outcome in ACC of the head and neck. Distant metastasis frequently develop, mainly in the first 5 years post treatment. Local recurrences often develop even later on, warranting long term follow up of patients treated for ACC. Grade III ACC should be considered a specific entity within the group of ACC due to its typical aggressive biological behavior and relatively poor outcome, implicating the need for an improved adjuvant treatment.
Head and neck squamous cell carcinoma (HNSCC) is typically regarded as a disease of elderly people. However, increasing numbers of patients worldwide with HNSCC at younger age (defined as <45 years ...old) have been reported in recent years.
To assess geographical variations and trends worldwide in incidence of oral and oropharyngeal cancer in young patients, a systematic review was conducted in PubMed and Google scholar databases from 1975 to June 2016. Seventy-eight studies were selected for further study.
Nineteen population-based studies on incidence rate were available from 13 countries, showing a prominent increase over time except for the Netherlands. A notable rise of oral (mobile) tongue cancer among white women and oropharyngeal cancer in white men was observed. Data suggest that cancer in young patients may be a distinct clinical entity and characterised by different aetiology and pathogenesis. Additionally, the relative proportion of oral and oropharyngeal cancer in young patients to total incidence revealed a significant difference between estimates from North America (5.5%) and both Africa (17.2%) and Middle East (14.5%).
It is concluded that (i) a rising trend in oral and oropharynx cancers is observed in young patients worldwide; (ii) incidence studies should properly define outcomes in age cohorts and use a consensus cut-off for young patients; (iii) more population-based studies should be performed in non-Western regions to get accurate global measures of incidence for these cancers in young subpopulations and (iv) there is an urge to identify new aetiological factors in these young patients.
•This systematic review assesses the global head and neck squamous cell carcinoma (HNSCC) incidence in young adults (<45 year).•In this group, a worldwide rising trend in HNSCC is observed.•Relative proportions of ‘young’ HNSCC versus total incidence vary between continents.•Data suggest that cancer in young patients may be a distinct clinical entity.•There is an urge to identify new aetiological factors in these young patients.
There is a great interest in developing biomarkers to enhance early detection and clinical management of tongue squamous cell carcinoma (TSCC). However, the developmental path towards a clinically ...valid biomarker remains extremely challenging. Ideally, the initial key step in moving a newly discovered biomarker towards clinical implementation is independent replication. Therefore, the focus of this review is on biomarkers that consistently showed clinical relevance in two or more publications.
We searched PubMed database for relevant papers across different TSCC sample sources, i.e., body fluids (saliva, serum/plasma) and tissues. No restriction regarding the date of publication was applied except for immunohistochemistry (IHC); only studies published between 2010 and June 2017 were included.
The search strategy identified 1429 abstracts, of which 96 papers, examining 150 biomarkers, were eventually included. Of these papers, 66% were exploratory studies evaluating single or a panel of biomarkers in one publication. Ultimately, based on studies that had undergone validation for their clinical relevance in at least two independent studies, we identified 10 promising candidates, consisting of different types of molecules (IL-6, IL-8, and Prolactin in liquid samples; HIF-1α, SOX2, E-cadherin, vimentin, MALAT1, TP53, and NOTCH1 in tissue biopsies) CONCLUSIONS: Although more exploratory research is needed with newer methods to identify biomarkers for TSCC, rigorous validation of biomarkers that have already shown unbiased assessment in at least two publications should be considered a high priority. Further research on these promising biomarkers or their combination in multi-institutional studies, could provide new possibilities to develop a specific panel for early diagnosis, prognosis, and individualized treatments.
The ∼15-kDa variable domains of camelid heavy-chain-only antibodies (called Nanobodies) can easily be formatted as multivalent or multispecific single-chain proteins.
Because of fast excretion, ...however, they are less suitable for therapy of cancer. In this study, we aimed for improved tumor
targeting of a bivalent anti–epidermal growth factor receptor (EGFR) Nanobody (αEGFR-αEGFR) by fusion to a Nanobody unit binding
to albumin (αAlb). Biodistributions of αEGFR-αEGFR, αEGFR-αEGFR-αAlb (∼50 kDa), αTNF-αTNF-αAlb (control, binding tumor necrosis
factor-α), and the ∼150-kDa anti-EGFR antibody cetuximab were compared in A431 xenograft-bearing mice. The proteins were radiolabeled
with 177 Lu to facilitate quantification. Tumor uptake of 177 Lu-αEGFR-αEGFR decreased from 5.0 ± 1.4 to 1.1 ± 0.1 %ID/g between 6 and 72 h after injection. Due to its rapid blood clearance,
tumor-to-blood ratios >80 were obtained within 6 h after injection. Blood clearance became dramatically slower and tumor uptake
became significantly higher by introduction of αAlb. Blood levels of αEGFR-αEGFR-αAlb were 21.2 ± 2.5, 11.9 ± 0.6, and 4.0
± 1.4 and tumor levels were 19.4 ± 5.5, 35.2 ± 7.5, and 28.0 ± 6.8 %ID/g at 6, 24, and 72 h after injection, respectively.
Tumor uptake was at least as high as for cetuximab (15.5 ± 3.9, 27.1 ± 7.9, and 25.6 ± 6.1 %ID/g) and significantly higher
than for αTNF-αTNF-αAlb. αEGFR-αEGFR-αAlb showed faster and deeper tumor penetration than cetuximab. These data show that
simple fusion of αEGFR and αAlb building blocks results in a bifunctional Nanobody format, which seems more favorable for
therapy as far as pharmacokinetics and tumor deposition are concerned. Mol Cancer Ther 2008;7(8):2288–97
Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a ...large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost.
Purpose
To understand why some patients respond to immunotherapy but many do not, a clear picture of the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is key. Here we ...review the current understanding on the immune composition per HNSCC subsite, the importance of the tumor’s etiology and the prognostic power of specific immune cells.
Recent Findings
Large cohort data are mostly based on deconvolution of transcriptional databases. Studies focusing on infiltrate localization often entail small cohorts, a mixture of HNSCC subsites, or focus on a single immune marker rather than the interaction between cells within the TME.
Summary
Conclusions on the prognostic impact of specific immune cells in HNSCC are hampered by the use of heterogeneous or small cohorts. To move forward, the field should focus on deciphering the immune composition per HNSCC subsite, in powered cohorts and considering the molecular diversity in this disease.
Summary 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.
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