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Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.

Introduction Carcinoma of unknown primary site (CUP) refers to 1–5% of all head and neck neoplasms. Very often, the primary site remains difficult to determine. Squamous cell carcinoma is the most frequent histopathological type diagnosed in the head and neck region. According to statistics, a primary site is usually located in the oropharynx. Study objective The study presents diagnostic difficulties and the methods of diagnosing and the therapy of CUP and primary sites in patients treated in the region of Lower Silesia and Silesia. The aim of the study was to show a retrospective analysis of 233 CUP patients to assess how clinical features, diagnosis and treatment affect the survival of patients. Material and methods The diagnostics of patients included panendoscopy with specimen collection (nasoendoscopy, laryngoscopy, esophagoscopy, brochoscopy), computed tomography examination of the neck, chest, abdomen and pelvis minor, as well as positron emission tomography examination. Tonsilletomy was performed in 37 patients. Neck dissection was carried out in 109 subjects and 165 patients were treated bt radiotherapy, and 135 by chemotherapy. Conclusions Tonsillectomy is required in CUP patients with the negative results of biopsy and imaging tests. It gives a possibility of detecting the primary site and improves the results of treatment and survival of CUP patients.Combination therapy, including surgical treatment and chemoradiotherapy, gives the best therapeutic results in CUP patients. The general condition of patient and younger age have an impact on prognosis and survival.

Background: Given the important role of ERCC4 gene in multiple DNA repair systems, we hypothesized that genetic variations within this gene may be a cervical squamous cell carcinoma (CSCC) risk and disease modulatory factor. Methods: In population-based, case-control association study including 143 CSCC patients and 207 healthy women, two ERCC4 tagSNPs were studied. Results: A significant protective effect against CSCC was observed assuming a dominant model in case of ERCC4rs3136176 ([AA]+[AT]vs.[TT]: p=0.04,OR=0.43), and genotype [AA] strongly protects against poorly (G3) differentiated CSCC (p correced= 0.008,OR=0.15) and significantly increased the disease remission rate (p=0.05,OR=0.48). A statistically significant increase frequency of ERCC4rs1799798 [A] allele was seen in patients with well differentiated (G1) CSCC (p=0.02, OR=2.40). Contrary, an opposite trend was observed when G1 was compared with G2 (moderately differentiated) CSCC (p=0.06). Furthermore, ERCC4rs1799798 [A] allele tended to be increased in patients with carcinoma planoepitheliale keratodes (Cpk) (p=0.07). Haplotype ERCC4rs3136176[A]/ERCC4rs1799798[G] significantly decreased risk of G1 as well as G3 CSCC (p=0.02,OR=0.50, and p=0.017,OR=0.42, respectively) and only tended to decrease risk of CSCC (p=0.07,OR=0.758) as well as carcinoma planoepitheliale akeratodes (Cpa) (p=0.059,OR=0.71). In contrast haplotype AA significantly increased risk of G1 CSCC and risk of Cpk (p=0.01, OR=2.51, and p=0.049, OR=1.96, respectively), whereas haplotype TG increased risk of G3 CSCC (p=0.037, OR=2.17). The overall survival rates showed similar mean survival rates according to patients' genotypes at both studied SNPs. Conclusion: The above findings consistently suggested that genetic variants in ERCC4 gene may play significant role in CSCC pathophysiology.

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