Detection of Human Papillomaviruses in the Nasopharynx of Breastfed Infants: New Findings and Meta-Analysis.

Vertical transmission of human papillomaviruses (HPVs) from mother to infant is known to occur during labor, delivery or breastfeeding. Infection with mucosal HPV 6 and 11 may cause recurrent respiratory papillomatosis in children, which is a rare and severe respiratory disease. The cutaneous HPV genotypes have also been described to be transmitted from mother to newborn through skin-to-skin contacts and during breastfeeding.

Modeling the epithelial-mesenchymal transition process in a 3D organotypic cervical neoplasia.

Here, we proposed an innovative organotypic cervical tumor model able to investigate the bi-directional crosstalk between epithelium and stroma as well as the key disease features of the epithelial-mesenchymal transition (EMT) process in vitro. By using a modular tissue assembling approach, we developed 3D cervical stromal models composed of primary human cervical fibroblasts (HCFs) or cervical cancer-associated fibroblasts (CCAFs) embedded in their own ECM to produce 3D normal cervical-instructed stroma (NCIS) or 3D cervical cancer-instructed stroma (CCIS), respectively. Then, we demonstrate the role of the tumor microenvironment (TME) in potentiating the intrinsic invasive attitude of cervical cancer derived SiHa cells and increasing their early viral gene expression by comparing the SiHa behavior when cultured on NCIS or CCIS (SiHa-NCIS or SiHa-CCIS).

The Role of microRNAs, Long Non-coding RNAs, and Circular RNAs in Cervical Cancer.

Prolonged infection of uterine cervix epithelium with human papillomavirus (HPV) and constitutive expression of viral oncogenes have been recognized as the main cause of the complex molecular changes leading to transformation of cervical epithelial cells. Deregulated expression of microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA) is involved in the initiation and promotion processes of cervical cancer development. Expression profiling of small RNAs in cervical neoplasia revealed up-regulated "oncogenic" miRNAs, such as miR-10a, miR-21, miR-19, and miR-146a, and down regulated "tumor suppressive" miRNAs, including miR-29a, miR-372, miR-214, and miR-218, associated with cell growth, malignant transformation, cell migration, and invasion.

Prevalence of "unclassified" HPV genotypes among women with abnormal cytology.

Background: High risk human papillomaviruses (HPVs) have been unequivocally recognised as the necessary cause of squamous intraepithelial lesions (SIL) and invasive carcinoma of the cervix. The distribution and the role of unclassified risk HPV genotypes in cervical neoplasia has not been fully elucidated.

Methods: Liquid-based cytological samples were collected from 337 women referred for colposcopy following an abnormal cytological diagnosis.

Human Oncoviruses and p53 Tumor Suppressor Pathway Deregulation at the Origin of Human Cancers.

Viral oncogenesis is a multistep process largely depending on the complex interplay between viruses and host factors. The oncoviruses are capable of subverting the cell signaling machinery and metabolic pathways and exploit them for infection, replication, and persistence. Several viral oncoproteins are able to functionally inactivate the tumor suppressor p53, causing deregulated expression of many genes orchestrated by p53, such as those involved in apoptosis, DNA stability, and cell proliferation.

Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.

Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma.

Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies.

An Engineered Cell-Instructive Stroma for the Fabrication of a Novel Full Thickness Human Cervix Equivalent In Vitro.

There is a growing interest for developing organotypic cervical models by using primary cervical cells that are able to reproduce the physiological relevant stromal microenvironment and the distinctive histology of the native cervical epithelium. Here for the first time it is reported the production of an organotypic cervical model featured by a scaffold-free stromal tissue resembling the extracellular matrix (ECM) composition and organization of the native counterpart as well as a completely well-differentiated epithelium. To reach this aim, human cervical microtissue precursors have been produced, characterized, and used as functional building units to fabricate a cell-synthesized cervical stroma equivalent by means of a bottom-up approach.

Tumor specific mutations in TERT promoter and CTNNB1 gene in hepatitis B and hepatitis C related hepatocellular carcinoma.

Recurrent somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene and in the exon 3 of CTNNB1 gene have been recognized as common events in hepatocellular carcinoma (HCC) with variable frequencies depending on etiology and geographical region. We have analyzed TERT promoter and CTNNB1 gene mutations in 122 cases of hepatitis B (HBV) and hepatitis C (HCV) related HCCs, in 7 cases of cholangiocarcinoma (CC) and hepatocholangiocarcinoma (HCC-CC) as well as in autologous cirrhotic tissues. Overall, 50.

Detection of human papillomavirus DNA in peri-tumor tissues and pelvic lymph nodes as potential molecular marker of micrometastasis in cervical cancer.

Background: The association between high risk human papillomaviruses (HPV) and cervical cancer has been firmly established. HPV genome is present in nearly all cases of cervical cancer and detection of viral DNA could therefore be used as a surrogate marker of micrometastasis in peri-tumor tissues and lymph nodes.

Methods: We analyzed primary cervical carcinomas, peri-tumor biopsies and pelvic lymph nodes in 20 women with invasive cancer (FIGO stage I-II) who underwent radical pelvic surgery and lymphadenectomy.

Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation.

Background: The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions.

Methods: A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL).

Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients.

The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26.

Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies.

Tobacco use and alcohol consumption are the main risk factors associated with head and neck squamous cell carcinoma (SCC) development due to their cytotoxic and mutagenic effects on the exposed epithelia of the upper aerodigestive tract. Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs), both encoding viral oncoproteins able to interfere with cell cycle control, have been recognized as the etiological agents of nasopharynx carcinoma and a fraction of oropharyngeal carcinoma, respectively. Head and neck SCC is a deadly disease and despite innovative treatments represents a major challenge for patients.

TP53 and PIK3CA gene mutations in adenocarcinoma, squamous cell carcinoma and high-grade intraepithelial neoplasia of the cervix.

Background: Mutations in the tumor suppressor gene TP53 and proto-oncogene PIK3CA and alterations of p53 and PIK3CA AKT mTOR pathways are common events in several human cancers. We focused on the analysis of TP53 and PIK3CA gene variations in adenocarcinoma, squamous cell carcinoma as well as in intraepithelial neoplasia grade 3 of the cervix.

Methods: DNA samples from 28 cervical adenocarcinoma, 55 squamous cell carcinoma and 31 intraepithelial neoplasia grade 3 (CIN3), previously characterized in terms of human papillomavirus (HPV) prevalence and genotype distribution, were analyzed for TP53 and PIK3CA mutations in the exons 4-9 and exon 9, respectively.

Somatic mutations of STK11 gene in human papillomavirus positive and negative penile cancer.

Background: Human papillomavirus (HPV) infection accounts for about 40-50% of all cases of penile carcinoma suggesting that other factors, including host genetic status, are involved in neoplastic transformation. In this perspective, STK11 gene, which has been found frequently mutated in HPV-related cervical carcinoma, has been analyzed in HPV-positive and HPV-negative invasive penile cancers to establish its mutational status and the possible correlation of HPV infection with specific genetic alterations.

Methods: Genomic DNAs extracted from 26 cases of penile squamous cell carcinoma were analyzed for genetic alterations in the exons 1 to 9 of STK11 gene by quantitative real-time PCR.

Characterization of the human papillomavirus (HPV) integration sites into genital cancers.

Oncogenic HPVs have been found frequently integrated into human genome of invasive cancers and chromosomal localization has been extensively investigated in cervical carcinoma. Few studies have analyzed the HPV integration loci in other genital cancers. We have characterized the integration sites of HPV16 in invasive penile carcinoma by means of Alu-HPV-based PCR.