Východisko a ciele: Zhubné nádory (ZN) hlavy a krku (skupina diagnóz C00–C14, podľa MKCH-10) tvoria heterogénnu skupinu ochorení s blízkou anatomickou lokalizáciou. Incidencia je 2–3-násobne vyššia u mužov ako u žien a celosvetovo narastá. Cieľom predkladanej analýzy je, pomocou vhodných štatistických analýz, odhadnúť časový vývoj incidencie a mortality spojených topografických lokalizácií ZN hlavy a krku a porovnať ho s časovým vývojom rovnakých ukazovateľov vo vybraných krajinách sveta. Ďalšími cieľmi bolo predikovať hodnoty incidencie a mortality prospektívne, analyzovať vekové ukazovatele ochorenia, podiely klinických štádií novodiagnostikovaných prípadov, ako aj odhadnúť bodovú prevalenciu ochorenia v Slovenskej republike (SR). Materiál a metódy: Podklady pre výpočty sa získali z národných databáz a výstupov Národného onkologického registra (NOR) SR (pričom sumárne údaje boli k dispozícii z národného epidemiologického portálu ZN, ktorý analyzoval dáta v r. 1984–2003 a bol dostupný do r. 2009, zvyšné pochádzali z výročných analýz NOR SR a z Národného centra zdravotníckych informácií (NCZI)), zo Štatistického úradu SR a z celosvetových databázových výstupov Medzinárodného úradu pre výskum rakoviny Svetovej zdravotníckej organizácie (IARC WHO) o incidencii, mortalite, prevalencii a prežívaní pacientov. Údaje o incidencii boli v SR k dispozícii do r. 2012 (vrátane) a o mortalite do r. 2020 (vrátane). Na analýzu vývoja časového trendu incidencie a mortality sa použil log-lineárny model joinpoint regresnej analýzy s využitím softvéru Joinpoint Regression Program. Pre dosiahnutie maximálneho spresnenia odhadovanej celkovej žijúcej populácie pacientov so ZN hlavy a krku sa vytvoril model na výpočet bodovej (celkovej) prevalencie, ktorý je založený na absolútnych číslach dlhodobo registrovaných národných počtoch novodiagnostikovaných pacientov, úmrtnosti na ochorenie, všeobecnej úmrtnosti a pravdepodobnosti prežívania. Zastúpenie klinických štádií ZN hlavy a krku na Slovensku sa spracovalo z dostupných národných dát (r. 2000–2012) a z predikcií, pričom vývoj nezohľadňuje zmeny v TNM klasifikáciách. Výsledky: Štandardizovaná incidencia a mortalita ZN hlavy a krku má u mužov na Slovensku signifikantne klesajúci trend od r. 1990, u žien sa však u oboch indikátorov dlhodobo zaznamenáva štatisticky významne nepriaznivo narastajúci trend, v prípade incidencie dokonca s prudkým zvýraznením vzostupu od r. 2004. Celková (štandardizovaná, ASR-W) incidencia aj mortalita ZN hlavy a krku na Slovensku boli v r. 2012 výrazne vyššie u mužov (ASR-W incidencia 22,6/100 000 a ASR-W mortalita 15,26/100 000) ako u žien (ASR-W incidencia 4,21/100 000 a ASR-W mortalita 1,52/100 000). K nepriaznivým trendom prežívania pacientov s týmto ochorením prispieva aj viac ako 75 % novodiagnostikovaných prípadov v lokálne pokročilých a metastatických klinických štádiách. Odhad absolútnej prevalencie tejto skupiny chorých v SR predstavuje k r. 2021 n = 9 395 pacientov. Záver: Aktuálne a validované epidemiologické výstupy pri ZN sú nevyhnutné pre plánovanie preventívnych a intervenčných programov v onkológii.
Background: Head-and-neck malignant neoplasms (diagnosis group C00-C14, according to ICD-10) form a heterogeneous group of diseases with close anatomical localization. The incidence is twice to three times higher in men than in women and is increasing worldwide. Objective: The aim of our analysis was to estimate changes of incidence and mortality rates of head-and-neck malignancies associated with anatomical topographic regions over the time as well as to compare these indicators in different selected countries of the world. Secondary endpoints included the assessment of patients’ age distribution, clinical stages of newly diagnosed cases, and point prevalence of the disease in the Slovak Republic (SR). Material and methods: The data base for the calculations was obtained from national databases and outputs of the National Cancer Registry (NCR) of the SR (with summary data available from the National Epidemiological Portal of Malignant Tumors, which analyzed data from 1984–2003 and was available until 2009, the remaining data were obtained from annual analyses of the NCR of the SR and the National Centre for Health Information (NCZI)), from the Statistical Office of the SR, and from the IARC WHO global database outputs on incidence, mortality, prevalence and survival of the patients. Incidence and mortality data in the SR were available up to 2012 (including) and up to 2021 (including), respectively. A log-linear joinpoint regression model was used to analyze the development of incidence and mortality rates over time by using Joinpoint Regression Program software. To achieve maximum precision in the estimated total surviving population of patients with head and neck malignant neoplasms, a model was developed to calculate the point (overall) prevalence based on absolute numbers of long-term registered national counts of newly diagnosed patients, mortality from the disease, overall mortality, and survival probability. The representation of clinical stages of head and neck carcinoma in the SR was compiled from available national data (2000–2012) and from predictions and does not consider changes in TNM classifications over the time. Results: The age-adjusted (to the world standard population, ASR-W) incidence rate and the age-adjusted (ASR-W) mortality rate of head-and-neck malignant tumors in the SR have shown a significantly decreasing tendency in men since 1990; however, in women both of these indicators have shown a significant increasing tendency, especially the significantly growing incidence since 2004. In 2012, the overall age-adjusted incidence and mortality rate of head-and-neck cancers in the SR were significantly higher in males (ASR-W incidence 22.6/100,000 and ASR-W mortality 15.26/100,000) compared to females (ASR-W incidence 4.21/100,000 and ASR-W mortality 1.52/100,000). More than 75% of newly diagnosed cases are already in advanced and metastatic clinical stages, which is the most unfavourable survival factor. The absolute prevalence of these patients in the SR was estimated to be N = 9,395 in the year 2021. Conclusion: It is necessary to get a current and well evaluated epidemiological overviews to be able to plan preventive and intervention programs in oncology.
- MeSH
- epidemiologické studie MeSH
- incidence MeSH
- lidé MeSH
- nádory hlavy a krku * epidemiologie mortalita MeSH
- prevalence MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Slovenská republika MeSH
Transfer-RNA-derived fragments (tRFs) are a class of small non-coding RNAs that are functionally different from their parental transfer RNAs (tRNAs). tRFs can regulate gene expression by several mechanisms, and are involved in a variety of pathological processes. Here, we aimed at understanding the composition and abundance of tRFs in squamous cell carcinoma of the head and neck (SCCHN), and evaluated the potential of tRFs as prognostic markers in this cancer type. We obtained tRF expression data from The Cancer Genome Atlas (TCGA) HNSC cohort (523 patients) using MINTbase v2.0, and correlated to available TCGA clinical data. RNA-binding proteins were predicted according to the calculated Position Weight Matrix (PWM) score from the RNA-Binding Protein DataBase (RBPDB). A total of 10,158 tRFs were retrieved and a high diversity in expression levels was seen. Fifteen tRFs were found to be significantly associated with overall survival (Kaplan-Meier survival analysis, log rank test p-value < 0.01). The top prognostic marker, tRF-20-S998LO9D (p < 0.001), was further measured in tumor and tumor-free samples from 16 patients with squamous cell carcinoma of the oral tongue and 12 healthy controls, and was significantly upregulated in tumor compared to matched tumor-free tongue (p < 0.001). Results suggest that tRFs are useful prognostic markers in SCCHN.
- MeSH
- databáze faktografické MeSH
- dlaždicobuněčné karcinomy hlavy a krku genetika mortalita MeSH
- Kaplanův-Meierův odhad MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory hlavy a krku genetika mortalita MeSH
- prognóza MeSH
- proteiny vázající RNA genetika MeSH
- RNA transferová genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. METHODS: p16/epidermal growth factor receptor (EGFR)/cluster of differentiation-44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. RESULTS: In the entire group and the p16 negative cohort, better 3-year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. CONCLUSION: Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.
- MeSH
- analýza přežití MeSH
- antigeny CD44 genetika MeSH
- dlaždicobuněčné karcinomy hlavy a krku * MeSH
- dospělí MeSH
- erbB receptory genetika MeSH
- geny p16 MeSH
- hodnocení rizik MeSH
- Kaplanův-Meierův odhad MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multivariační analýza MeSH
- nádory hlavy a krku * genetika mortalita radioterapie MeSH
- přežití bez známek nemoci MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- radioterapie s modulovanou intenzitou * metody MeSH
- regulace genové exprese u nádorů * MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
PURPOSE OF REVIEW: The role of HPV in oropharyngeal cancer is well recognized. HPV DNA is also found in a fraction of head and neck tumors outside of oropharynx but its clinical importance is unknown. The purpose of this review is to sum up the present knowledge about the prevalence and possible impact of HPV presence in head and neck tumors in nonoropharyngeal sites. RECENT FINDINGS: The data demonstrating prevalence of HPV presence in tumors outside of oropharynx are inconsistent. However, it can be stated that it is substantially lower than in oropharynx. Most articles report the HPV DNA presence only but very few prove also the transcriptionally active viral presence. The fraction of really HPV-induced tumors is probably very small. The majority of literature shows no impact of HPV on prognosis in nonoropharyngeal locations. Also the role of high-risk HPV in malignant transformation of lesions potentially linked to malignancy like inverted papillomas, recurrent respiratory papillomatosis or laryngeal dysplasia was up to date not demonstrated. SUMMARY: Despite of the unknown role of HPV and lack of evidence regarding any clinical use of HPV knowledge in other than oropharyngeal tumors, further research is warranted.
- MeSH
- DNA virů izolace a purifikace MeSH
- infekce papilomavirem komplikace MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádorové biomarkery izolace a purifikace MeSH
- nádory hlavy a krku mortalita virologie MeSH
- Papillomaviridae izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: For some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors. METHODS: Nine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5-144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm3 (range 0.8-22.6 cm3), and the median margin dose was 12.5 Gy (range 10-18 Gy). Patients with neurofibromatosis were excluded from this study. RESULTS: The median follow-up was 51 months (range 6-266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm3 (p = 0.037) and non-dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5-38 months). Six patients underwent repeat SRS at a median of 64 months (range 44-134 months). Four patients underwent resection at a median of 14 months after SRS (range 8-30 months). CONCLUSIONS: Stereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.
- MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mikrochirurgie metody MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory hlavy a krku diagnostické zobrazování mortalita chirurgie MeSH
- následné studie MeSH
- neurilemom diagnostické zobrazování mortalita chirurgie MeSH
- radiochirurgie metody MeSH
- reoperace MeSH
- reziduální nádor mortalita chirurgie MeSH
- senioři MeSH
- tumor glomus jugulare diagnostické zobrazování mortalita chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Three-weekly high-dose cisplatin (100 mg/m2) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, due to unsatisfactory patient tolerance, various weekly low-dose schedules have been increasingly used in clinical practice. The aim of this meta-analysis was to compare the efficacy, safety, and compliance between these two approaches. MATERIALS AND METHODS: We systematically searched literature for prospective trials of patients with LA-SCCHN who received postoperative or definitive conventionally fractionated concurrent chemoradiation. Radiation doses were usually 60-66 gray (Gy) in the postoperative setting and 66-70 Gy in the definitive setting. Standard, three-weekly high-dose cisplatin (100 mg/m2, 3 doses) was compared with the weekly low-dose protocol (≤50 mg/m2, ≥6 doses). The primary endpoint was overall survival. Secondary outcomes comprised response rate, acute and late adverse events, and treatment compliance. RESULTS: Fifty-two studies with 4,209 patients were included in two separate meta-analyses according to the two clinical settings. There was no difference in treatment efficacy as measured by overall survival or response rate between the chemoradiation settings with low-dose weekly and high-dose three-weekly cisplatin regimens. In the definitive treatment setting, the weekly regimen was more compliant and significantly less toxic with respect to severe (grade 3-4) myelosuppression (leukopenia p = .0083; neutropenia p = .0024), severe nausea and/or vomiting (p < .0001), and severe nephrotoxicity (p = .0099). Although in the postoperative setting the two approaches were more equal in compliance and with clearly less differences in the cisplatin-induced toxicities, the weekly approach induced more grade 3-4 dysphagia (p = .0026) and weight loss (p < .0001). CONCLUSION: In LA-SCCHN, current evidence is insufficient to demonstrate a meaningful survival difference between the two dosing regimens. Prior to its adoption into routine clinical practice, the low-dose weekly approach needs to be prospectively compared with the standard three-weekly high-dose schedule. IMPLICATIONS FOR PRACTICE: Given concurrently with conventional radiotherapy in locally advanced head and neck cancer, high-dose three-weekly cisplatin has often been replaced with weekly low-dose infusions to increase compliance and decrease toxicity. The present meta-analysis suggests that both approaches might be equal in efficacy, both in the definitive and postoperative settings, but differ in toxicity. However, some toxicity data can be influenced by unbalanced representation, and the conclusions are not based on adequately sized prospective randomized studies. Therefore, low-dose weekly cisplatin should not be used outside clinical trials but first prospectively studied in adequately sized phase III trials versus the high-dose three-weekly approach.
- MeSH
- adherence pacienta statistika a číselné údaje MeSH
- chemoradioterapie škodlivé účinky metody MeSH
- cisplatina aplikace a dávkování MeSH
- dávka záření MeSH
- frakcionace dávky záření MeSH
- klinické zkoušky jako téma MeSH
- leukopenie chemicky indukované epidemiologie MeSH
- lidé MeSH
- nádory hlavy a krku mortalita patologie terapie MeSH
- nauzea chemicky indukované epidemiologie MeSH
- neutropenie chemicky indukované epidemiologie MeSH
- rozvrh dávkování léků MeSH
- spinocelulární karcinom mortalita patologie terapie MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvracení chemicky indukované epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- srovnávací studie MeSH
BACKGROUND: c-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. METHODS: Immunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. RESULTS: All 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. CONCLUSIONS: The present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladý dospělý MeSH
- nádory hlavy a krku genetika metabolismus mortalita MeSH
- nádory jazyka genetika metabolismus mortalita MeSH
- protoonkogenní proteiny c-myc biosyntéza genetika MeSH
- regulace genové exprese u nádorů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom genetika metabolismus mortalita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- časové faktory MeSH
- cetuximab škodlivé účinky terapeutické užití MeSH
- dlaždicobuněčné karcinomy hlavy a krku farmakoterapie mortalita sekundární virologie MeSH
- infekce papilomavirem virologie MeSH
- klinické rozhodování MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory hlavy a krku farmakoterapie mortalita patologie virologie MeSH
- protinádorové látky imunologicky aktivní škodlivé účinky terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- rizikové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
V posledních letech dochází k nárůstu incidence nádorů hlavy a krku, které nejsou spojeny s anamnézou kouření a alkoholu. Tyto nádory jsou způsobeny infekcí vysoce rizikovými typy lidského papilomaviru (HPV) a postihují zejména tonzily a kořen jazyka. Od nádorů způsobených primárně abúzem tabáku se odlišují rozdílným biologickým chováním i výrazně lepší prognózou. HPV status je významným prognostickým faktorem, nicméně dosud není prediktivním faktorem pro výběr léčebné modality. V současnosti probíhá řada studií pro pouze HPV-pozitivní nebo HPV-negativní dlaždicobuněčné karcinomy orofaryngu.
In recent years, an increasing incidence of tumors of head and neck region that are not associated with a history of smoking and alcohol was captured. These tumors are almost regularly caused by an infection of high risk human papillomavirus (HPV) and affect mostly the tonsils and the base of the tongue. Compared to tobacco-related cancers they differ markedly in biologic behaviour and carry better prognosis. Although a strong prognostic factor, HPV status is still not a predictive factor for the selection of treatment modality, but there are many ongoing studies for either HPV-positive or HPV-negative oropharyngeal squamous cell carcinoma.
- MeSH
- infekce papilomavirem epidemiologie patofyziologie MeSH
- lidé MeSH
- nádory hlavy a krku * epidemiologie mortalita virologie MeSH
- nádory orofaryngu epidemiologie patologie prevence a kontrola virologie MeSH
- spinocelulární karcinom epidemiologie mortalita prevence a kontrola virologie MeSH
- tonzilární nádory epidemiologie mortalita prevence a kontrola virologie MeSH
- vakcíny proti papilomavirům terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Integration, which leads to the disruption of the circular HPV genome, is considered as a critical, albeit not obligatory, step in carcinogenic progression. Although cervical carcinomas with extrachromosomal HPV plasmid genomes have been described, the virus is integrated in 70% of HPV16-positive cervical tumours. Limited information is available about HPV integration in head and neck tumours (HNC). In this study, we have characterised the physical status of HPV in a set of tonsillar tumour samples using different methods--the mapping of E2 integration breakpoint at the mRNA level, the 3' RACE based Amplification of Papillomavirus Oncogene Transcripts (APOT) assay and Southern blot. Furthermore, the impact of HPV integration on patients' prognosis has been evaluated in a larger set of 186 patients with head and neck cancer. Based on the analysis of E2 mRNA, HPV was integrated in the host genome in 43% of the HPV-positive samples. Extrachromosomal or mixed form was present in 57%. In fresh frozen samples, the APOT and E2 mapping results were in agreement. The results were confirmed using Southern blotting. Furthermore, the type and exact site of integration were determined. The survival analysis of 186 patients revealed HPV positivity, tumour size and lymph node positivity as factors that influence disease specific survival. However, no statistically significant difference was found in disease specific survival between patients with HPV-positive integrated vs. extrachromosomal/mixed forms of the virus.
- MeSH
- infekce papilomavirem komplikace virologie MeSH
- integrace viru genetika MeSH
- lidé MeSH
- nádory hlavy a krku mortalita virologie MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- Southernův blotting MeSH
- spinocelulární karcinom virologie MeSH
- tonzilární nádory virologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH