Presence and activity of HPV in primary lung cancer.

PURPOSE: Evaluate the presence of human papillomavirus (HPV) in biopsies of Brazilian patients with lung cancer and also the expression of the E6 and E7 oncoproteins. HPV is widely known as an important condition for cervical cancer although evidence today shows it is associated with several other types of cancer and may also be involved in lung cancer development. However, there are some divergences regarding the presence and activity of HPV in lung carcinogenesis. METHODS: The detection of HPV was performed by PCR, followed by genotype and immunohistochemical evaluation of E6 and E7 HPV type specific, from 63 patients. RESULTS: HPV was found to be present in 33 of the 63 samples, and types 16 and 18 were detected with frequencies of 81% (27/33) and 19% (6/33), respectively. About the presence of the virus in different histological types of tumors, HPV was detected in squamous cell carcinoma (39.39%), followed by adenocarcinoma (33.33%) and small cell carcinoma (18.18%) and large cell carcinoma (9.1%). The presence of the E6 (antibody anti-HPV 16 and anti-HPV 18) and E7 (antibody anti-HPV 16 and anti-HPV 18) oncoproteins was detected by immunohistochemical stain technique in 28/33 samples and 25/33 samples, respectively. CONCLUSIONS: Our results suggest that the lung tumor patients have high prevalence of HPV and the virus is not only present but also active in tumor cells. Therefore, the HPV is probably playing a role in lung carcinogenesis.

Viral Modulation of TLRs and Cytokines and the Related Immunotherapies for HPV-Associated Cancers.

The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human papillomavirus- (HPV-) related cancers. This virus is able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. Both TLRs and cytokines play a central role in HPV recognition, cell maturation and differentiation as well as immune signalling. Therefore, the imbalance of this sensitive control of the immune response is a key factor for developing immunotherapies, which strengthen the host immune system to accomplish an efficient defence against HPV and HPV-infected cells. Based on this, the review is aimed at exposing the HPV immune evasion mechanisms involving TLRs and cytokines and at discussing existing and potential immunotherapeutic TLR- and cytokine-related tools.

hrHPV E5 oncoprotein: immune evasion and related immunotherapies.

The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

Expression Profile of MicroRNA-203 and its ΔNp63 Target in Cervical Carcinogenesis: Prospects for Cervical Cancer Screening.

BACKGROUND/AIM: Host molecules disturbed by human papillomavirus (HPV) oncoproteins have been shown to be potential biomarkers of cervical carcinogenesis and represent an alternative or supplementary aid to cytological testing and HPV detection. The miR-203 and one of its targets, ΔNp63, are known to be host molecules that interact with each other to control the proliferation and differentiation of keratinocytes; both have been found to be dysregulated in many cancers. As the role of p63 and miR-203 in cervical carcinogenesis is not yet well-understood, we have, thus, decided to evaluate the changes of expression of both in cervical carcinogenesis. MATERIALS AND METHODS: This study was carried out by obtaining quantitative polymerase chain reaction (qPCR) data from cervical biopsies. RESULTS: miR-203 and ΔNp63 displayed a similar expression pattern across cervical tissues and both targets showed statistically significant differences between low-grade squamous intraepithelial lesion (LSIL) x high-grade squamous intraepithelial lesion (HSIL); HSIL x Cancer. Additionally, we did not observe an inverse correlation between ΔNp63 mRNA and miR-203 levels as expected but, rather, a positive correlation between cervical tissues. CONCLUSION: Although preliminary, the expression levels of ΔNp63 mRNA and miR-203 seem to be promising for cervical cancer screening. In addition, positive correlation between miR-203 and ΔNp63 expression suggests the possible existence of some indirect pathways. However, further studies are needed to clarify the role of ΔNp63 and miR-203 in cervical carcinogenesis and, thus, determine how they can be applied in new strategies for diagnosis.