BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases.

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

PD-L1 and PD-1 expression in thyroid follicular epithelial dysplasia: Hashimoto thyroiditis related atypia and potential papillary carcinoma precursor.

Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.

Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile.

Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diagnosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. OBJECTIVES: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. METHOD: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. RESULTS: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5-5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8-1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9-10.8%) in benign, 29.2% (95% CI: 25.0-33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6-28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1-22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2-8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). CONCLUSIONS: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.

Follicular Epithelial Dysplasia as Hashimoto Thyroiditis-Related Atypia: a Series of 91 Specimens.

Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1-3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma.

The Role of Cell Blocks and Immunohistochemistry in Thyroid Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Bethesda Category.

INTRODUCTION: Thyroid cytology is a widely accepted tool in the clinical triaging of nodular lesions. Cell blocks (CBs) can help in the diagnosis of atypical lesions, namely, thyroid Bethesda category of Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). METHODS: In a series of 224 AUS/FLUS thyroid samples with CB, we studied CB cellularity and feasibility of 3 immunohistochemical markers (cytokeratin 19 [CK19], HBME-1, and galectin-3) apart and in combination. RESULTS: The CBs were non-diagnostic in 34 cases. Twenty-four CBs contained <10 cells, 45 CBs 10-50 cells, and 121 CBs >50 cells. Notably, more cellularity was found in CBs performed by plasma-thrombin and in-house techniques (p < 0.001). The diagnostic accuracy to detect malignancy was 65.1% for CK19, 72.1% for HBME-1, and 70.3% for galectin-3. CONCLUSION: In conclusion, CB cellularity is essential for successful immunohistochemistry application and further diagnostic workup of AUS/FLUS cases.

Multifunctional Roles of miR-34a in Cancer: A Review with the Emphasis on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer with Clinical Implications.

MiR-34a belongs to the class of small non-coding regulatory RNAs and functions as a tumor suppressor. Under physiological conditions, miR-34a has an inhibitory effect on all processes related to cell proliferation by targeting many proto-oncogenes and silencing them on the post-transcriptional level. However, deregulation of miR-34a was shown to play important roles in tumorigenesis and processes associated with cancer progression, such as tumor-associated epithelial-mesenchymal transition, invasion, and metastasis. Moreover, further understanding of miR-34a molecular mechanisms in cancer are indispensable for the development of effective diagnosis and treatments. In this review, we summarized the current knowledge on miR-34a functions in human disease with an emphasis on its regulation and dysregulation, its role in human cancer, specifically head and neck squamous carcinoma and thyroid cancer, and emerging role as a disease diagnostic and prognostic biomarker and the novel therapeutic target in oncology.

IgG4-positive plasma cells in Hashimoto thyroiditis: IgG4-related disease or inflammation-related IgG4-positivity?

Despite the interest of researchers in IgG4-related disease (IgG4-RD), many questions still remain unanswered regarding the thyroid gland. We aimed to clarify the relationship between IgG4-positive plasma cells and the histopathological pattern in the Hashimoto thyroiditis (HT) in a Finnish series. HT specimens (n = 280) were retrieved from the Department of Pathology, Fimlab Laboratories. After re-evaluation, 82 (29%) cases (72 females and 10 males, 52 ± 17 years) with significant fibrosis were selected. CD38, IgG and IgG4 positivity in plasma cells was evaluated by immunohistochemistry. Adjusted IgG4-positive plasma cells per HPF > 20 and IgG4- to IgG-positive plasma cell ratio > 30% were adopted as threshold criteria and related to other morphological features. IgG4-positive HT group included 13 cases (15% from fibrotic HT, 4.6% from all HT, 50 ± 15 years, 11 females) with adjusted HPF count 30 ± 5 (23-40) IgG4-positive cells. IgG4-positivity significantly correlated with the presence of lobulation, oncocytic metaplasia and certain type of fibrosis, fibrosis spread outside the gland, lymphocytes/plasma cells epithelial penetration, the predominance of microfollicles and follicular atrophy in the present study. Despite the persisting uncertainty whether HT is IgG4-RD, HT with IgG4-positive plasma cells is histopathologically distinct entity with some geographic variability.

The role of fine-needle aspiration biopsy (FNAB) in the diagnostic management of parotid gland masses with emphasis on potential pitfalls.

PURPOSE: The treatment strategy of parotid gland tumours depends mainly on the histopathological type of the lesion. Fine-needle aspiration biopsy (FNAB) is recommended in preoperative diagnostics. The aim of the study was to evaluate the FNAB standing in the diagnostic algorithm of parotid gland lesions and to correlate FNAB results in relation to the definitive histopathological diagnosis. MATERIAL AND METHODS: The retrospective analyses of 651 examined and consequently surgically treated parotid gland lesions at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague between 2006 and 2016 were used. Preoperative cytological results were consequently evaluated in relation to the definitive histopathological diagnosis. RESULTS: The cohort consisted of 367 women and 284 men (average age 58 years). FNAB was diagnostic in 604 (92.8%) patients and non-diagnostic in 47 (7.2%) patients. The result of FNAB was positive (suspicious for malignant tumour) in 89 (14.7%) patients and negative (benign) in 515 (85.3%) patients. Sensitivity of the examination was 80.00%, specificity was 93.82%, PPV 62.92%, NPV 97.28%, and LR + and LR- were 12.95 and 0.21, respectively, with an accuracy of 92.22%. CONCLUSION: Our results confirm the significant role of FNAB in the diagnostic algorithm of parotid gland lesions.

Pretreatment Serum Levels of Soluble Cytokeratin Fragments (Cyfra 21-1, TPS, MonoTotal) in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay. PATIENTS AND METHODS: In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels. RESULTS: Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors. CONCLUSION: The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation.

Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. PATIENTS AND METHODS: A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. RESULTS: Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. CONCLUSION: The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection).

MicroRNA profile in site-specific head and neck squamous cell cancer.

BACKGROUND/AIM: MicroRNAs (miRs) are non-coding RNA molecules regulating diverse cellular processes essential in carcinogenesis. Little is known regarding miRs in head and neck squamous cell cancer (HNSCC). The aim of the present study was to investigate miRs in relation to the clinico pathological features of site-specific HNSCC. MATERIALS AND METHODS: The study comprised of 51 patients with HNSCC (23 oropharyngeal, 24 laryngeal and 4 hypopharyngeal carcinomas). Total RNA was extracted from tumor tissue and normal squamous epithelium using the miRNeasy FFPE Kit. A quantitative estimation of let-7a, miR-21, miR-200c, miR-34a, miR-375 was performed by a real-time polymerase chain reaction (PCR) method using the TagMan® MicroRNA assay. Additionally, p16 expression was detected by immuno histo chemistry. RESULTS: Significant differences of let-7a, miR-200c, miR-34a levels between oropharyngeal and laryngeal cancers were found (p<0.05). Compared to non-neoplastic tissues, miR-21, miR-200c, miR-34a were up-regulated and miR-375 was down-regulated in tumors of all sites. MiR-34a tumor levels significantly correlated with oropharyngeal origin (p=0.0284) and p16 positivity (p=0.0218). CONCLUSION: The microRNA profile seems to play a potential role in the pathobiology of oropharyngeal and laryngeal HNSCC. Up-regulation of miR34a in p16-positive oropharyngeal cancer has not been so far described and additional studies are warranted.

Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration.

OBJECTIVE: MicroRNAs (miRs) are noncoding, single-stranded regulatory RNA molecules involved in the posttranscriptional regulation of gene expression. They control the development and maintenance of the diverse cellular processes including proliferation, differentiation, motility and apoptosis. Expression of miRs is tissue-specific and each alteration of the tissue miR profile is associated with a distinct disease status. STUDY DESIGN: We reviewed the literature on the expression of miRs in thyroid tumors, focusing on methodology and diagnostic and prognostic output. Separately, we analyzed 11 studies on miR profiles in thyroid cytological material. RESULTS: Numerous studies have evaluated the miR profiles of thyroid tumors in an attempt to find a possible diagnostic and prognostic role. Both downregulation and upregulation of numerous miRs was found, but differences between the surgical pathology specimens and corresponding fine-needle aspirates in the expression of the same miRs were also reported. CONCLUSIONS: The results from surgically resected material cannot be extrapolated into preoperative use without validation. For diagnostic use, the strong overlap between follicular adenoma and follicular carcinoma miR profiles is challenging. In summary, miR-221 and miR-222 are consistently upregulated in different types of thyroid carcinomas and might be used as markers of malignancy.

Analysis of preoperative serum levels of MMP1, -2, and -9 in patients with site-specific head and neck squamous cell cancer.

BACKGROUND: Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing common etiological factors. Serum levels of MMP1, MMP2, and MMP9 were analyzed in patients with oropharyngeal, laryngeal, and hypopharyngeal carcinomas in an effort to elucidate the pathobiology and in order to find useful biomarkers of site-specific HNSCC. PATIENTS AND METHODS: The study group comprised of 46 patients with HNSCC (21 with oropharyngeal, 21 with laryngeal and 4 with hypopharyngeal cancer). Serum levels of MMP1, -2, and -9 were determined by the MAGPIX multiplex method. P16 protein was detected by immunohistochemistry. Serum levels of matrix metalloproteinases (MMPs) were correlated with clinicopathological features of carcinomas and were compared with respect to tumor site. RESULTS: Significant correlations were confirmed between p16 positivity and oropharyngeal cancer, MMP1 and p16 positivity, and recurrence and smoking. Statistically significant differences in serum levels of MMPs between cancer of different locations were not found. CONCLUSION: MMP1 expression is significantly affected by smoking habit and by p16 and might mediate etiopathogenetical process in cancerogenesis of HNSCC. Our pilot study did not establish any utility of MMP1, -2, or -9 in clinical practice as diagnostic/prognostic markers.

[Up-to-date experience with the international classification system Bethesda 2010 for thyroid fine-needle aspirate: a review]. / Prehled dosavadních zkuseností s mezinárodní klasifikací tenkojehlové aspiracní cytologie stítné zlázy Bethesda 2010.

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in thyroid fine needle aspiration cytology (FNAC) in 2010. A six-tier system is generally accepted. Bethesda categories include morphologic description, risk of malignancy and follow-up suggestions in each group. The system has its advantages and disadvantages, that are discussed. The most problematic are the categories of "Atypia of undetermined significance" or "Follicular lesion of undetermined significance" (AUS/FLUS). The group is heterogenous and overused thus far. The possibilities of its improvement are discussed. The Bethesda system does not include any prognostic and predictive markers. However, they represent the promising direction in the improved version of the BSRTC. Novel molecular methods and alternative techniques such as core needle biopsy are briefly discussed.

Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste garbage?

OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in thyroid cytology in 2007 and is now generally accepted. BSRTC categories include a morphologic description and risk of malignancy as well as follow-up suggestions in each group. However, the category entitled 'atypia of undetermined significance or follicular lesion of undetermined significance' (AUS/FLUS) is problematic. This category is heterogeneous and has been overused so far. STUDY DESIGN: Twenty-six studies were included in a meta-analysis. In addition to AUS/FLUS percentage, we analysed repeated AUS/FLUS percentage, cytological and histological correlations, and risk of malignancy and neoplasm for AUS/FLUS. Furthermore, stratification, inter- and intra-observer variability, and the possibility of a switch to another category and its clinical consequences were reviewed. RESULTS: Out of a total of 81,833 cases, AUS/FLUS accounted for 10.9%, with a 34% risk of malignancy. Persistent AUS/FLUS was found in 21.6% in repeated cytology. Cytohistological correlation was analysed from 16 studies (4,964 cases), revealing 10.4% as AUS/FLUS and a 21.5% risk of malignancy. CONCLUSIONS: An AUS/FLUS category seems to be currently reasonable with clearly defined cytomorphological criteria which do not correspond unequivocally with those of the other categories. An AUS/FLUS category is justified and possible means of its improvement with immunohistochemistry, molecular analysis and imaging are discussed.

The role of protein p16(INK4a) in glottic laryngeal squamous cell carcinoma.

Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing the common etiological factors. However some differences in pathogenesis and prognosis of HNSCC have been hitherto documented. Laryngeal squamous cell carcinoma (LSCC) is one the most common type of the head and neck cancer. The majority of laryngeal cancers are located in the glottic area. P16 was recently documented to be important prognostic marker in many tumors including HNSCC. The aim of our study was to assess the significance of p16 expression in glottic LSCC. Fifty eight patients after surgical treatment of the glottic LSCC were enrolled in the retrospective study. The p16 expression was immunohistochemically detected and semiquantitatively evaluated in tumor tissue. The results were statistically correlated with clinical and pathological parameters. Protein p16 was expressed in glottic LSCC of 15 patients (25.9 %). Statistically significant higher p16 overexpression was proven in non-smokers in comparison with smokers (75 % versus 18 %; p =0.003). Recurrent cancer was diagnosed in 8 patients (13.8 %), and all these tumors were p16 negative. Our study shows, that p16 expression in glottic LSCC especially in subgroup of non-smokers might be promising prognosticator of better clinical outcome in routine practice. The p16 status did not statistically correlate with cervical lymph node metastases or with grading and staging of cancers, respectively. The preliminary results suggest that p16 overexpression in glottic LSCC may identify patients at low risk of disease recurrence. However, the pathobiology of this tumor as well as predictive role of p16 expression in laryngeal cancer still remains to be better elucidated.

[Vitamin D in relation to head and neck cancer]. / Vitamin D ve vztahu ke karcinomu hlavy a krku.

Vitamin D was lately introduced as the important anti-cancer agent with therapeutic potential to be used in prevention and therapy of malignant tumors. Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Prognosis of this cancer is in most patients poor. In attempts to improve therapy of this cancer, contemporary research is focused on extension of the etiological and pathobiological aspects of cancerogenesis of HNSCC. This fact provoked us to summarize present scientific knowledge about etiopathological, chemopreventive and therapeutic role of vitamin D in head and neck squamous cancer and outline the direction of further research in this interesting and from clinical point of view important field. Key words: head and neck squamous cell carcinoma - anti-tumor effect - vitamin D.