Persistent infection with high-risk human papillomavirus (HPV) genotypes is the leading cause of cervical cancer development. To this end several studies have focused on designing molecular assays for HPV genotyping, which are considered as the gold standard for the early diagnosis of HPV infection. Moreover, the tendency of HPV DNA to be integrated into the host chromosome is a determining event for cervical oncogenesis. Thus, the establishment of molecular techniques was promoted in order to investigate the physical status of the HPV DNA and the locus of viral insertion into the host chromosome. The molecular approaches that have been developed recently facilitate the collection of a wide spectrum of valuable information specific to each individual patient and therefore can significantly contribute to the establishment of a personalised prognosis, diagnosis and treatment of HPV-positive patients. The present review focuses on state of the art molecular assays for HPV detection and genotyping for intra-lesion analyses, it examines molecular approaches for the determination of HPV-DNA physical status and it discusses the criteria for selecting the most appropriate regions of viral DNA to be incorporated in HPV genotyping and in the determination of HPV-DNA physical status.

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.

Background/Objectives: Persistent infection with high-risk (HR) HPV genotypes is the main risk factor for the development of cervical cancer. The present analysis provides recent trends on HR-HPV infection rates and the distribution of HR-HPV genotypes among 3500 Greek women between 2021 and 2023. Methods: The detection of HR-HPVs and the specific identification of HPV16 and HPV18 were conducted using the Roche Cobas 4800 HPV assay. The genotyping of 12 other HR-HPV genotypes was performed through the Nested Multiplex PCR methodology (NMPCR). Results: The overall infection rate was 8.8% with the most prevalent HR-HPV genotype being HPV16 followed by HPV31, HPV66, HPV56, HPV51, HPV58, HPV45, HPV18, HPV68, HPV59, HPV52, HPV35, HPV39, and HPV33. Among HR-HPV-positive cases the prevalence of single, double, triple, and quadruple infections was 73.9%, 19.9%, 5.5%, and 0.7%, respectively. Age-specific analysis showed that the HR-HPV infection rate was higher in the age group of 31–35 years (25.5%) and it was estimated that multiple infections occur more often in younger women. Notably, the distribution of HR-HPV genotypes varies among different age groups. It is proposed that HPV16, HPV31, HPV56, and HPV66 may show an increased possibility of establishing long-term infections in Greek women over 36 years old. Conclusions: The high rates of specific HR-HPVs which are not included in the prophylactic vaccines underlines the significance of constant surveillance of circulating HPVs in the Greek population.

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.