BACKGROUND We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

e22518Background: Cancer patients in developing and low income countries have limited access to target therapies. Many patients with gastrointestinal stromal tumors (GIST) have had to wait for exte...

Introduction: Skin melanoma has been one of the most researched malignant melanoma of today. Its "popularity" among the researchers and clinicians arises from variety of forms and biological behaviour, it's characteristic appearance, genetic and immunologic certainty and its prognostic uncertainty. Patients and methods: We analyzed 62 patients with a primary skin melanoma diagnosed in the period from January 2001, to June 2010 (patients were divided in two groups; Group A: patients with melanoma development based on pre-existed nevi and Group B: de novo melanomas). The clinicopathological parameters determined for each tumour were histological type, Breslow thickness, Clark level, and pathological disease stage. The results were correlated with expression of estrogen receptor beta (Ers) and Bcl2. Results: Comparing individual groups according to the intensity of positivity in relation to the stage of Clark, we recognize differences in the distribution of patients with pre-existent nevi (group A), but not in de novo melanoma (group B). Significant differences between individual groups for Ers and Bcl2 expression in terms of intensity of positivity in relation to Clark level (III/IV) showed differences in distribution in patients with pre-existing nevi (Group A). After adjusting for age and sex, we found that Ers and Bcl2 expression was significantly higher in patient with pre-existing nevi in higher melanoma tissue compared with thin melanoma tissue. Conclusion: Expression of ER in Clark level III and IV is higher in melanoma arising from pre-existing nevi, giving better chance of survival to our patients in comparison to de novo melanoma.

Introduction   Pap smear, the main tool of cervical cancer screening is not always available, but some patients are in urgent need for proper diagnostic. Aim of this article was to investigate accuracy of colposcopy for detection of squamous intraepithelial lesions of low or high grade (LGSIL, HGSIL) and to promote colposcopy as useful tool for detection of patients in need for immediate further diagnostics.  Methods Prospective multicentric study performed in BH 95% CI = 42.024 to 5713.304).  HGSIL was confirmed in 27 (87%) cases by histology (CIN II /CIN III). There were no statistically significant differences between colposcopic finding and histology results (Yates-corrected χ2 = 0.33 P = .5637) Conclusions This study showed high level of correlation between colposcopy and PAP results    (63-64%) and to histology for HGSIL (87%). In absence of PAP test colposcopy could be used to select patients in need for biopsy.

AIM To investigate the ovarian cancer incidence for the period 1996-2010 in the Federation Bosnia and Herzegovina (FBandH) emphasizing that there is no official cancer database for that period. METHODS This retrospective study analyzed ovarian cancer incidence in the period 1996-2000 and an estimation of incidence for the period 2000-2010 based on this data, as well as on 2007 -2010 incidence according to the Federal Public Health Institute. RESULTS The incidence of ovarian cancer in the period 1996-2000 was 3.68-6.38/100.000. The estimate of incidence for the period 2000-2010 resulted with the rate of 14.6 at the end of the analyzed period. According to the Federal Public Health Institute, incidence for the period 2007-2010 was 11.4-12.4/100.000. CONCLUSION According to different sources incidence of ovarian cancer in the Federation BH varies from 11.4-12.4/100.000, which is lower than the incidence for Southern Europe and neighboring countries. Incidence published by the International Agency for Research on Cancer (2008) for BH (both entities) was 10.1/100.000. An increasing trend of incidence is evident too. However, in FBiH a cancer database does not exist, while the system of cancer registration does not function or operate without proper coordination. A further main task for health authorities is to establish a functional system of cancer registration and a database, which would enable a follow-up and work on prevention and early detection of ovarian cancer.

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16INK4a expression.

We present a review of the current implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 central and eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and The Former Yugoslav Republic of Macedonia. At least one current HPV prophylactic vaccine is registered in all central and eastern European countries except Montenegro. Six counties-Bulgaria, the Czech Republic, Latvia, Romania, Slovenia, and Former Yugoslav Republic of Macedonia-have integrated the HPV vaccination into their national immunization program and currently provide routine vaccination free of charge to the primary target population. Ten countries have not integrated HPV vaccination into the national immunization program. The key reasons for lack of implementation of HPV vaccination into the national immunization program are the high vaccine cost and negative public perception. Vaccination of males is not recommended in any country in the region.

The burden of cervical cancer in central and eastern Europe is generally higher compared to western or northern Europe due to a history of mostly opportunistic cervical cancer screening practices and due to the strong influence of political and economic changes in post-communist transition. This article describes the current cervical cancer screening practices, organizational plans for the future, and main obstacles that need to be overcome in 16 countries in central and eastern Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and The former Yugoslav Republic of Macedonia. Unfortunately, only a few countries have managed to establish an organized and well-functioning cervical cancer screening program in recent years, whereas most countries in the region are still struggling with implementation-related issues of organized cervical cancer screening. Encouragingly, even in the countries where only opportunistic screening is performed, well-prepared plans and strategies have been established for switching to organized screening in the near future.

Angiogenesis is a critical event in the development, progression, and spread of various human cancers, including lung cancer. Molecular mechanisms that underlie the complex regulation of angiogenic processes are poorly understood. However, an increasing body of evidence indicates miRNAs as important regulators of tumor angiogenesis. Forceps biopsies were collected from tumor tissue, surrounding tissue, and non-tumor tissue from 50 NSCLC patients. Lung tissue samples from individuals with no clinical evidence of a cancerous disease served as controls. Immunohistochemical staining for Factor VIII was used to evaluate microvessel density (MVD). TaqMan® primer-probe sets were used in quantitative real-time RT-PCR reactions to determine expression levels of let-7b, miR-126, miR-9, and miR-19a. We demonstrated significantly higher MVD and decreased expression levels of let-7b and miR-126 in tumor tissue and surrounding tissue in comparison to corresponding non-tumor tissue or lung tissue from the control group. In addition, no differences in MVD and expression levels of both miRNAs between tumor tissue and surrounding tissue from NSCLC patients were observed. Low expression of both miRNAs correlated with high MVD and worse progression-free survival and overall survival. These observations strongly suggest similar molecular alternations within tumor tissue and surrounding tissue that comprise a specific microenvironment. Low expression of let-7b and miR-126 seems to have a possible anti-angiogenic role in lung tumor tissue and significantly correlates with worse survival outcomes for lung cancer patients. Moreover, the regulation of let-7b and miR-126 expression could have therapeutic potential because it could reduce tumor angiogenesis and therefore suppress tumor growth in lung cancer patients.

32 squamous lung carcinoma, 18 lung adenocarcinoma and 45 healthy individuals were included. let-7b and miR-126 expression were detected by real-time RT-PCR. 3 tissues of lung cancer patients (tumor, tumor surroundings and healthy lung tissue) were compared. Expression of anti-angiogenic let-7b and miR-126 were significantly lower in tumor tissue and surroundings compared to both healthy lung tissue of diseased patients and control. There was no difference between tumor and tumor surrounding tissue. High let-7b expression and miR-126 expression were highly associated with both better progression-free and overall survival. High micro-vascular density was negatively associated to let-7b and miR-126 expression and highly associated with poor overcome. Our results confirm a possible role of those two miRNas in lung cancer angiogenesis and suggest the potential new target angiogenic lung cancer therapy.

Primary rectal adenocarcinoma metastatic to the breast is an exceedingly rare event. Its management differs from that of primary breast cancer, as illustrated by this case. A 63-year-old woman presented with a breast lump 30 months after abdominoperineal resection for rectal adenocarcinoma, stage T₃N₁M₀ (stage III), followed by standard postoperative radiochemotherapy. The patient underwent a mammography and ultrasonography. A CT scan of the abdomen showed metastatic disease. An excisional biopsy of the breast lump was performed; morphological features were identical to the original rectal cancer. Immunohistochemical results were negative for estrogen and progesterone receptors and gross cystic disease fluid protein-15, and intensity positive for cytokeratin 20 and carcinoembryonic antigen. The patient died after treatment with palliative chemotherapy. Metastatic disease from rectal carcinoma to the breast is a marker for disseminated metastatic spread with poor prognosis.