Colposcopic findings to study cervical changes in reproductive age group women using various contraceptives.

BACKGROUND: Colposcopy has a key role to play in see-and-treat programs for premalignant cervical lesions. The aim of the study/was to observe cervical changes with a colposcope using the Swede scoring system in fertile age group women using various contraceptives: conventional methods (barrier methods, coitus interruptus), oral contraceptives (OCPs), copper-T and bilateral tubectomy. The aim of the study was to observe and evaluate the colposcopic findings using the Swede scoring system for the diagnosis of premalignant/malignant lesions in reproductive age group women using various contraceptives. METHODS: This was a prospective observational study, conducted among 200 women of reproductive age group using various contraceptives in a tertiary care institute in North India. PAP smear, direct visual examination, VIA (Visual Inspection with Acetic Acid) examination, colposcopic examination, and (biopsy if indicated) were done. The data were collected, and analysis was done using Microsoft Excel Office Software 2019 version 19.11 and epi info (CDC Atlanta) 7.23.1. Statistical analysis was done using percentages, mean, mode, median, standard deviation, Chi-square, Fisher's Test, and Anova Test. RESULTS: We found positive PAP (Papanicolaou test) smears in 61.50%, positive VIA examination in 9%, and positive findings in colposcopic examination in 28.50%, Swede score of 0-3 in 100% (0-91%, 1-2%, 2-6%, and 3-1%) and positive biopsy in 9% subjects. Malignant findings were observed in 1.00% of PAP smears. Colposcopic findings were CIN 1 (cervical intraepithelial neoplasia 1) in 8.5% and CIN 2 in 0.5% subjects. Swede score was zero in 91%, 1 in 2%, 2 in 6%, and 3 in 1% of subjects. HPE (histopathological examination) was chronic cervicitis in 8.50% and mild dysplasia/CIN 1 in 0.5%. No significant statistical associations between contraceptive choice and false-positive test results or disease prevalence was found in any group except Cu-T users p = 0.0184 (especially for CIN 2; p = 0.0109 and CIN 1 more in all groups than Cu-T users). Colposcopy had sensitivity 100%, specificity 91.46% (0/0 = 0%) PPV = 5.56%, NPV = 100%, Accuracy = 91.5% for detecting mild dysplasia/CIN-non-significant (p = 0.055). Our study had mainly low-grade lesions with 100% NPV. With increase in Swede Score, sensitivity increases but at the expense of specificity but it was statistically non-significant (p = 0.055). CONCLUSIONS: Our study may guide the rational use of colposcopy with Swede scoring for see-and-treat lesions, which is easy and with a low learning curve, as a tool for diagnosis but only in cases where indicated like unhealthy cervix because of the high rate of false-positive results. In low-grade lesions, it is highly useful to rule out the disease.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

Role of DNA methylation-based mitotic ageing indices in oral cancer development and recurrence.

OBJECTIVE: DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation-derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence-free survival (RFS). METHODS: DNA methylation-based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non-malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA-HNSCC). Differences in mitotic indices between non-malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs. RESULTS: In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non-malignant and premalignant oral tissues. HPV-positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24-5.48). CONCLUSIONS: DNA methylation-derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation-derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non-malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted.

Impact of hyperglycemia on the expression of GLUT1 during oral carcinogenesis in rats.

BACKGROUND: On the background of the epidemiological link between diabetes and oral cancer, the present study aimed to analyze the potential involvement of selected glucose transporters (GLUT1/GLUT3/GLUT4), if any, in such putative association. METHODS AND RESULTS: Oral carcinogenesis was induced by 4-nitroquinoline N-oxide in 10 non-diabetic and 10 diabetic rats; 8 non-diabetic and 7 diabetic rats served as controls. Expressions of selected GLUTs at mRNA and protein levels were analyzed in oral tissue (normal/lesion) by quantitative real-time PCR and immunohistochemistry respectively. Premalignant lesions (hyperplasia/dysplasia/carcinoma-in-situ) appeared on tongues of carcinogen-treated animals. Significant increase of GLUT1mRNA level was seen from normal to lesion tongues, along increasing lesion grades (from hyperplasia/mild dysplasia to moderate/severe dysplasia) and in lesions induced under hyperglycemic condition than that induced under normoglycemic one; a similar trend was found in transcript variant-1 of GLUT1, but not in variant-2. GLUT3 and GLUT4 mRNA levels were comparable among lesions irrespective of grades and glycemic status. Concordant to mRNA level, overall expression of GLUT1 protein was higher in tongue lesions in presence of hyperglycemia than in absence of such condition; non-lesion portions of tongues exposed to carcinogen showed a similar trend. Moreover in carcinogen-treated groups, non-lesion and lesion portions of tongues under hyperglycemic condition showed predominantly membranous expression for GLUT1 which was again significantly higher than equivalent portions of tongue under normoglycemic condition. CONCLUSION: Hyperglycemia seemed to favor GLUT1 over-expression and membrane localization of the protein during oral carcinogenesis. GLUT1 transcript variant-1 appeared to be more important than variant-2 in disease pathogenesis.

Premalignant Disorders of the Breast in Pregnancy and Lactation.

Papillomas, atypical hyperplasias, and lobular carcinoma in situ of the breast are not malignant tumors, but present serious management challenges when they are diagnosed in a breast biopsy . Upgrading after excision and increased possibility of future cancer are risks that accompany these lesions. While some features have been defined as high-risk for upgrading, many practitioners now recommend conservative non-surgical treatment and vacuum-assisted biopsy . However, the challenge gets worse when the patient is pregnant or breastfeeding because of the limitations in imaging and treatment in relation to the fetus. This chapter deals with these problems, although the best management strategy cannot be defined because of lack of evidence at present.

Vascular alterations after photodynamic therapy mediated by 5-aminolevulinic acid in oral leukoplakia.

Impairment of vascular functions after photodynamic therapy (PDT) is frequently associated with tumor remission and is considered one of the main antineoplastic PDT effects. Vascular alterations in oral leukoplakia (OL) treated with PDT have not yet been described. The aim of this study was to evaluate the effect of topical 5-ALA-mediated PDT on the vascular network of 4NQO-induced OL in rats. After applying 4NQO topically on the tongue during 16 weeks, there was induction of dysplastic lesions, which were treated with two PDT sessions (with an interval of 72 h between them), using topical application of 5-ALA and posterior irradiation with a laser (90 J/cm2 fluency). Histological sections of the tongues were obtained and analyzed concerning plasmatic exudation and microvessel density after immunolabeling with CD31 and CD34 vessel markers. There was intense plasmatic exudation after 6 h of the first PDT session; at 6 h of the second PDT session, there was a significant reduction in the density of CD31- and CD34-positive microvessels in comparison to controls (p < 0.05). In the PDT intervals, there was an increase in the density of CD31 and CD34 microvessels, suggesting angiogenesis. Topical application of 5-ALA-mediated PDT caused an immediate deleterious effect on the vascular network, increasing vessel permeability and reducing vessel density, mainly after two sessions of the treatment. However, secondary angiogenesis emerged in these lesions during intervals of the PDT session. This fact may be considered during the adoption of a PDT protocol, to avoid OL resistance and recurrence after the treatment.

Gene expression of miRNA-138 and cyclin D1 in oral lichen planus.

OBJECTIVES: This study aimed to evaluate microRNA-138 (miR-138) gene expression and its target cyclin D1 (CCND1) gene and protein expression in oral lichen planus (OLP) mucosa in an attempt to investigate their possible roles in OLP immunopathogenesis. METHODS: Sixty oral biopsy specimens were harvested from 30 healthy subjects and 30 OLP patients, subdivided into reticular, atrophic, and erosive groups (n = 10 each). Samples were subjected to quantitative real-time polymerase chain reaction analysis for quantification of miR-138 and CCND1 relative gene expression and immunohistochemical analysis to determine CCND1 protein expression. RESULTS: Samples from OLP patients had a significant underexpression of miR-138 gene and overexpression of CCND1 at both gene and protein levels compared to normal mucosa samples. The lowest levels of miR-138 expression were observed in atrophic and erosive OLP compared to reticular OLP, and the highest levels of CCND1 gene and protein expression were in atrophic OLP. An inverse correlation was demonstrated between the miR-138 expression and both CCND1 gene and protein expression in OLP patients. A significant positive correlation between CCND1 gene and protein expression was also observed. CONCLUSION: Downregulation of miR-138 increases the gene and protein expression of its potential target CCND1 in OLP mucosa which might have a pivotal role in the disease pathogenesis. CLINICAL RELEVANCE: This research implied that miR-138 may have a role in identification of symptomatic OLP lesions. MiR-138 might be considered as a potential tool in future OLP molecular therapy.

Icaritin Reduces Oral Squamous Cell Carcinoma Progression via the Inhibition of STAT3 Signaling.

Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.

Estimation of Expression of Oral Fluid Biomarkers in the Diagnosis of Pretumor Diseases of Oral Mucosa.

Complex clinical, dental, and morphological investigation, and ELISA of levels of MMP-2, 8, 9, and TIMP-1 and 2 in the saliva was performed during primary examination of patients with premalignant lesions of maxillofacial area and practically healthy volunteers. Levels of all study MMP in the saliva significantly differed (p≤0.05) in patients with premalignant lesions and the control. These patients were also characterized by a significant (0.1≤p≤0.05) changes in TIMP concentrations (toward pathological pattern) comparing to the control. Pattern of correlations between parameters of MMP-2 expression might be a marker for early diagnostics of a premalignant lesion independently on the dental health. Observed features of biomarker expression in patients with premalignant lesions might reflect the appearance of a cascade of biochemical reactions followed by the activation of production of proteinases and their inhibitors as a response to the exposure to etiological factors. Clinical and morphological diagnosis of a premalignant lesion in the maxillofacial area was confirmed by the immunological analysis of biomarker expression in the saliva, which can be used for monitoring and screening of population.

The performance of Dynamic Spectral Imaging colposcopy depends on indication for referrals.

OBJECTIVE. A previous study has shown that Dynamic Spectral Imaging (DSI) colposcopy increases the sensitivity of the colposcopic examination in women referred with abnormal cytology. In this study we have reanalyzed the performance of DSI and conventional colposcopy for new referral conditions and for low-grade cytology referrals versus high-grade cytology referrals. METHOD. Data from a previous validation trial was used to assess the performance of DSI in different cytology groups:Women referred with BMD (borderline and mild dyskaryosis) cytology and women referred with NBMD cytology either hrHPV positive or negative were separately analyzed. Furthermore, we tried to assess the clinical performance by appropriate filtering of patients to replicate two different referral strategies. RESULTS. The sensitivity of DSI and conventional colposcopy to detect CIN2+ lesions in women referred with BMD cytology is 82% and 44% respectively (p= 0.001) and in the NBMD group 77% and 64% respectively (p= 0.24). If the two techniques are combined the sensitivity is 85%.When the conditions of new screening strategies are applied DSI colposcopy has a higher sensitivity to detect CIN2+ than conventional colposcopy. Findings are similar when CIN3+ is used as a threshold. CONCLUSION. We found that in most cases DSI colposcopy has a higher sensitivity than conventional colposcopy, even when referral criteria are changed. Unlike conventional colposcopy, the sensitivity of colposcopy with DSI in low-grade cytology referrals was found similar to the sensitivity in high-grade cytology referrals. This suggests that a baseline colposcopy sensitivity may be possible with the adjunctive use of the DSI map, irrespective of referral cytology.

Salivary and serum level of CYFRA 21-1 in oral precancer and oral squamous cell carcinoma.

BACKGROUND: CYFRA 21-1, a constituent of the intermediate filament proteins of epithelial cells, is known to be increased in many cancers. This study was designed to estimate the levels of salivary and serum CYFRA 21-1 in patients with oral precancer and oral squamous cell carcinoma (OSCC) and compare them with healthy controls. MATERIALS AND METHODS: Each group comprised of 100 subjects. Saliva and blood samples were collected from patients with OSCC, premalignant subjects, and normal healthy subjects. Serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. Appropriate statistical tests were employed to assess diagnostic potency of CYFRA 21-1. RESULTS: We found a significant increase in CYFRA 21-1 level in OSCC compared with PML and healthy subjects. Salivary CYFRA 21-1 levels in OSCC was threefold higher when compared to serum levels. PML group showed increased salivary CYFRA 21-1 when compared to control subjects, but it was significantly lower compared with OSCC. Receiver operator characteristic curve analysis showed salivary CYFRA 21-1 to have superior sensitivity in detecting OSCC compared with serum CYFRA 21-1. CONCLUSIONS: The outcome of this study suggests that salivary CYFRA 21-1 can be utilized as a biomarker in early detection of oral cancer.

Visceral abdominal fat measured by computed tomography is associated with an increased risk of colorectal adenoma.

We investigated whether visceral adipose tissue (VAT) measured by computed tomography (CT) is a risk factor for colorectal adenoma. For a total of 1,328 patients (857 without adenoma, 471 with colorectal adenoma) undergoing colonoscopy and CT, associations between colorectal adenoma and body mass index (BMI), VAT area and subcutaneous adipose tissue (SAT) were assessed using odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for age, sex, family history, smoking, alcohol intake, diabetes mellitus, aspirin use and nonsteroidal anti-inflammatory drug use. Multivariate analysis showed that colorectal adenoma was marginally associated (p=0.06) with BMI, but not with SAT, while it was significantly associated with VAT and the VAT to SAT ratio (VAT/SAT) for both categorical data and trend (p<0.05). When the obesity indices were considered simultaneously, colorectal adenoma remained significantly associated with VAT and VAT/SAT (p<0.05), but not BMI and SAT. In patients with colorectal adenoma, the adjusted OR for the highest quartiles of VAT and VAT/SAT was 1.90 (95% CI 1.16-3.13) and 2.25 (95% CI 1.49-3.41), respectively, compared to the lowest quartiles. Only VAT area was significantly associated with colorectal adenoma in both men and women (p<0.05). Proximal, multiple and advanced adenomas had significantly higher VAT areas (p<0.05) than distal, solitary and nonadvanced adenomas. Our findings implicate abdominal VAT in the development and progression of colorectal adenoma, and it was better obesity index for colorectal adenoma than BMI in both sexes.

Oral premalignant lesions: epidemiological and clinical analysis in the northern Polish population.

INTRODUCTION: Leukoplakia is the most common potentially malignant condition of the oral cavity. AIM: Epidemiological and clinical analysis of patients with oral leukoplakia (OL) diagnosed and treated in the Department of Maxillofacial and Oral Surgery, Medical University of Gdansk. MATERIAL AND METHODS: The study was retrospective and prospective. Among 55 911 patients diagnosed and treated in the Department in 1999-2009, 204 people with OL were selected. The material includes 104 women and 100 men with an average age of 58.1. Most of the patients were in the age group of 50-70 years, average age was 58.1. RESULTS: The most common concomitant disease was diabetes. More than 88% of the patients declared occurrence of OL predisposing development factors (50.49% - cigarette smoking). Three hundred and twenty foci of OL were found among patients. Homogeneous OL dominated (72.05%). Multifocal OL was diagnosed in 58.3% of patients. The most common location of lesions was buccal mucosa (52.2%). Cancers developed on the basis of OL in 7 patients (3.43%). The percentage of malignant transformation was 12.19% for untreated patients and 1.41% for treated patients. The floor of the oral cavity was proven to be the location of the highest risk of oral squamous cell carcinoma. Patients with diabetes may be more likely to develop OL. The risk of malignant transformation is relatively high. In our material it was equal to 3.43%. CONCLUSIONS: Cigarette smoking is the most important factor, which can influence the effectiveness of treatment.

Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions.

Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis on protein-coding transcripts. We reanalyzed a publicly available RNA-Seq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript and gene abundance were quantified using kallisto, while differential expression and transcript usage analysis was performed utilizing sleuth and RATs packages. Functional characterization involved overrepresentation analysis via clusterProfiler, weighted coexpression network analysis (WGCNA), and network analysis via Enrichr-KG. We detected 5906 differentially expressed transcripts and 4626 genes, exhibiting significant enrichment within pathways associated with oxidative phosphorylation and mitochondrial function. Remarkably, transcript-level WGCNA revealed a single module correlated with dysplasia status, notably enriched in cilium-related biological processes. Notable hub transcripts included RABL2B (ENST00000395590), DNAH1 (ENST00000420323), EFHC1 (ENST00000635996), and VWA3A (ENST00000563389) along with transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant bronchial lesion biology, including identification of potential biomarkers associated with early lung carcinogenesis.

Immune profiling of premalignant lesions in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development. OBJECTIVE: This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps. METHODS: Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes. RESULTS: Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid-derived suppressor cells (MDSCs). CONCLUSION: The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

Evaluation of silica spin­column and magnetic bead formats for rapid DNA methylation analysis in clinical and point­of­care settings.

Late-stage cancers lack effective treatment, underscoring the need for early diagnosis to improve prognosis and decrease mortality rates. Molecular markers, such as DNA methylation, offer promise in early cancer detection. The present study compared commercial kits for analyzing DNA from cervical liquid cytology samples in cancer screening. Rapid bisulfite conversion kits using silica spin-columns and magnetic beads were assessed against standard DNA extraction and bisulfite conversion methods for profiling DNA methylation using quantitative methylation-specific PCR. ß-actin amplification indicated the suitability of small sample volumes for methylation studies using either the pellet or supernatant (cell-free DNA) parts. Comparison of Bisulfite Conversion Kit-Whole Cell (Abcam), Methylamp Bisulfite Modification (Epigentek), EpiTect Fast LyseAll Bisulfite Kit (Qiagen GmbH) and EZ DNA Methylation-Direct Kit (Zymo Research Corp.) showed no significant differences in ß-actin cycle threshold values. EZ-96 DNA Methylation-Lightning MagPrep (Zymo Research Corp.), a hybrid kit in a 96-well plate format, exhibited swift turnaround time and similar amplification efficiency. Automation with magnetic bead kits increased throughput without compromising amplification efficiency in open PCR systems. Cost analysis favored direct kits over the gold standard manual protocol. This comparison aids in selecting cost-effective DNA methylation diagnostic tests. The present study confirmed comparable kit performance in methylation-based analysis, highlighting the adequacy of cytology samples and the potential of bodily fluids as alternatives for liquid biopsy.

Short telomere lengths in peripheral blood leukocytes are associated with an increased risk of oral premalignant lesion and oral squamous cell carcinoma.

BACKGROUND: Oral premalignant lesions (OPLs) are precursors of oral squamous cell carcinoma (OSCC). Short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers. However, it is unclear whether short leukocyte telomere length (LTL) predisposes individuals to OPL and OSCC. METHODS: LTL was measured in PBLs from 266 patients who had a diagnosis of either OPL (N = 174) or OSCC (N = 92) and from 394 age-matched and sex-matched controls. The association between LTL and the risk of OPL or OSCC, as well as the interaction of telomere length, cigarette smoking, and alcohol drinking on the risk of OPL or OSCC, were analyzed. RESULTS: The age-adjusted relative LTL was shortest in the OSCC group (1.64 ± 0.29), intermediate in the OPL group (1.75 ± 0.43), and longest in the control group (1.82 ± 0.36; Ptrend < .001). When the analysis was dichotomized at the median value in controls, adjusting for age, sex, smoking status, and alcohol drinking status, the odds ratio for the risk of OPL and OSCC associated with short LTL was 2.03 (95% confidence interval, 1.29-3.21) and 3.47 (95% CI, 1.84-6.53), respectively, with significant dose-response effects for both associations. Among 174 patients with OPL, 23 progressed to OSCC, and the mean LTL was shorter in progressors than in nonprogressors (mean ± standard deviation: 1.66 ± 0.35 vs 1.77 ± 0.44, respectively), although the difference did not reach statistical significance (P = .258), probably because of the small number of progressors. An interaction analysis identified short LTL, smoking, and drinking alcohol as independent risk factors for OPL and OSCC. CONCLUSIONS: Short LTL was associated with increased risks of developing OPL and OSCC. The current results also indicated that short LTL likely predisposes patients to the malignant progression of OPL.

[Precursors of breast cancer]. / Prekurzory karcinomu prsu.

It has become apparent that estrogen receptor (ER) - positive and - negative breast lesions are completely distinct diseases. Precursors of low-grade breast cancer are low-grade premalignant lesions, usually ER and progesterone receptor (PR) positive and HER2 negative. On the other hand, precursors of high-grade breast cancer are high-grade premalignant lesions, usually ER and PR negative and HER2 positive. Lobular neoplasia (LN) and ductal carcinoma in situ (DCIS) are important from the clinical point of view. LN increases the risk of bilateral breast cancer. This is why the recommendation for the treatment of LN is very different -  from just following up up to bilateral mastectomy. The complete surgical excision of the lesion with negative margins is the usual treatment of DCIS. Several big randomized clinical trials showed the benefit of adjuvant radiotherapy (RT). Some of them suppose that there is a group of patients who do not need adjuvant treatment. The benefit of adjuvant tamoxifen is clear only for patients with ER positive disease. The UK/ ANZ study showed the benefit of tamoxifen only in patients without RT.

[Precancerous conditions in the ENT area]. / Prekancerózy v ORL oblasti.

An important part of tumor prevention is early detection, dia-gnosis, treatment and screening of precancerous conditions. Correct detection and screening of premalignant lesions leads to early dia-gnosis of a malignant process which provides a better chance to completely cure the patient and also predicts better quality of life. Precancerous conditions look like whitish, red or mixed mucose lesions (leukoplakia, erytroplakia, erytroleukoplakia) which are visible during clinical examination. Nevertheless, these mucose changes are not absolutely conclusive. Therefore, histological testing is necessary for dia-gnosis and determination of bio-logical potencial of precancerous lesions. Precancerous lesions as a term of histological terminology means dysplasia. The risk of progression of dysplasia into a carcinoma depends on a grade of dysplasia. The conservative or surgical treatment is chosen according to localisation and grade of dysplasia.

Crossroads: the role of biomarkers in the management of lumps in the breast.

Premalignant lesions in the breast pose a difficult decision-making problem, whether to treat proactively and accept the side effects or to engage in watchful waiting and possibly encounter a later diagnosis of invasive cancer. A biomarker or set of biomarkers to inform on the individual progression risk would be beneficial to the patient and cost-effective for the healthcare system. The gene products of tumor progression may be expressed in early non-cancerous ("premalignant") lesions, where they are associated with a high probability for full transformation in breast cancers. One such molecule is the OPN splice variant-c. OPN-c is also present in a fraction of the premalignant lesions, where it reflects an elevated risk for progression to cancer within 5 years, regardless of the lesion's subtype. This marker has the properties needed to facilitate decisions to treat at the premalignant stage.