Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6 : Q14H, H78Y, L83V, Ε7 : N29S, S63F, E2 : H35Q, P219S, T310K, E5 : I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

The causal relationship between HPV and cervical cancer in association with the high prevalence of high risk HPV genotypes led to the design of HPV vaccines based on the major capsid L1 protein. In recent years, capsid protein L2 has also become a focal point in the field of vaccine research. The present review focuses on the variability of HPV16 L1 and L2 genes, emphasizing the distribution of specific amino acid changes in the epitopes of capsid proteins. Moreover, a substantial bioinformatics analysis was conducted to describe the worldwide distribution of amino acid substitutions throughout HPV16 L1, L2 proteins. Five amino acid changes (T176N, N181T; EF loop), (T266A; FG loop), (T353P, T389S; HI loop) are frequently observed in the L1 hypervariable surface loops, while two amino acid substitutions (D43E, S122P) are adjacent to L2 specific epitopes. These changes have a high prevalence in certain geographic regions. The present review suggests that the extensive analysis of the amino acid substitutions in the HPV16 L1 immunodominant loops may provide insights concerning the ability of the virus in evading host immune response in certain populations. The genetic variability of the HPV16 L1 and L2 epitopes should be extensively analyzed in a given population.

Breast cancer is the most common type of cancer in females and is the leading cause of cancer‑associated death among women, worldwide. The present study aimed to measure the serum levels of fatty acid‑binding protein 4 (FABP4), retinol binding protein 4 (RBP4) and the MMP‑9/neutrophil gelatinase‑associated lipocalin (NGAL) complex in women diagnosed with breast cancer. Serum levels of the examined proteins were determined in the peripheral blood of patients via ELISA. Furthermore, whether the concentration of each protein was associated with breast cancer growth, molecular subtype, BMI, postmenopausal status, diabetes and the social background of patients was assessed. Women with invasive breast cancer demonstrated significantly higher levels of FABP4 (P=0.008). Additionally, considerably elevated FABP4 levels were demonstrated specifically in Luminal breast cancer cases (P<0.01). No significant association was recorded between RBP4 and breast cancer development. In addition, significantly lower levels of the MMP‑9/NGAL complex were recorded in triple negative/HER‑2 cases (P<0.05). BMI values appeared to influence the aforementioned associations, while significantly high serum levels of FABP4 and the MMP‑9/NGAL complex were found in postmenopausal patients with breast cancer and a BMI ≥25 kg/m² (P<0.05). In addition, high levels of FABP4 were significantly associated with breast cancer patients with diabetes (P=0.05). However, no association was identified between RBP4, the MMP‑9/NGAL complex and diabetes. In conclusion, FABP4 can be regarded as a biomarker of breast cancer growth, while both FABP4 and the MMP‑9/NGAL complex may provide considerable information regarding the development of specific breast cancer subtypes. FABP4 and the MMP‑9/NGAL complex may also be able to predict the development of breast cancer in postmenopausal patients with obesity.

Angiogenesis is a biological process that involves the formation of new blood vessels from the existing vasculature, and it plays a fundamental role in the development and progression of several types of cancer, including lung cancer. The angiopoietin/Tie2 ligand/receptor system orchestrates vascular integrity. In particular, Angiopoietin-1 activates the endothelial cell (EC)-specific receptor tyrosine kinase,Tie2,which is essential for preserving endothelial quiescence. On the other hand, Angiopoietin-2 acts as an inhibitor of the Angiopoietin-1/Tie2 signaling pathways, thus facilitating the destabilization of quiescent endothelium in cases of inflammation and cancer. Clinical studies have proven that high levels of Angiopoietin-2 indicate the development of non-small-cell lung carcinomas (NSCLC), while high levels of Angiopoietin-2 are strongly related to tumor angiogenesis, lymphangiogenesis, metastasis, and poor prognosis. Interestingly, the association of Angiopoietin-2 levels with the type of surgical approach makes Angiopoietin-2 a valuable factor in selecting the most suitable therapeutic strategy for lung cancer patients. The role of the Angiopoietin-1 and Angiopoietin-4 levels in NSCLC development requires further investigation. The present review focuses on the clinical impact of the Angiopoietin-1, Angiopoietin-2, and Angiopoietin-4 levels in patients diagnosed with NSCLC, emphasizing the interaction between them, and how they affect the development, progression, and metastasis of lung disease. Finally, it estimates the role of angiopoietins levels in the effective therapy of lung cancer patients.

Previous analyses have identified certain but limited evidence of recombination among HPV16 genomes, in accordance with a general perception that DNA viruses do not frequently recombine. In this evolutionary/bioinformatics study we have analyzed more than 3600 publicly available complete and partial HPV16 genomes. By studying the phylogenetic incongruence, similarity plots and the distribution patterns of lineage-specific SNPs, we identify several potential recombination events between the two major HPV16 evolutionary clades. These two clades comprise the (widely considered) phenotypically more benign (lower risk) lineage A and the (widely considered) phenotypically more aggressive (higher risk) non-European lineages B, C and D. We observe a frequency of potential recombinant sequences ranging between 0.3 and 1.2% which is low, but nevertheless considerable. Our findings have clinical implications and highlight that HPV16 genotyping and risk assessment based only on certain genomic regions and not the entire genome may provide a false genotype and, therefore, its associated risk estimate. Finally, based on this analysis, we have developed a bioinformatics tool that automates the entire process of HPV16 lineage genotyping, recombination detection and further identifies, within the submitted sequences, SNPs that have been reported in the literature to increase the risk of cancer.

Angiopoietin-2 (Ang-2) has been implicated in the development of several types of cancer, including lung malignancy. In the present study, we examined the impact of Ang-2 serum concentration on the development, dissemination, and 5-year overall survival of NSCLC and SCLC. A total of 99 patients with lung cancer were tested. The OS of NSCLC and SCLC patients was estimated using Kaplan–Meier curves and compared through log-rank test. The median serum level of Ang-2 at baseline in both NSCLC and SCLC patients was significantly higher than that of controls (p < 0.0001). The Ang-2 serum concentration was not related to metastasis, neither in NSCLC nor in SCLC cases. The OS was found to be significantly shorter for stage IIIβ NSCLC patients with a high baseline Ang-2 serum concentration (p = 0.012), while Cox regression analysis showed that Ang-2 is a significant independent factor for poor prognosis for stage IIIβ NSCLC (hazard ratio = 2.97, 95% CI: 1.05–8.40, p = 0.04). The concentration of Ang-2 has no impact on the prognosis of SCLC. Ang-2 could be considered as a significant molecular marker that enables the prediction of NSCLC and SCLC development, and is involved in the poor prognosis of stage IIIβ NSCLC.