Human Papillomaviruses As Therapeutic Targets in Human Cancer

Abstract

A B S T R A C TCervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. HPV oncoproteins contribute to cancer initiation and progression and their expression is necessary for the maintenance of the transformed state. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression, is common to almost all cervical cancers offers unique opportunities for prevention, early detection, and therapy. The potential for prevention has been realized by introduction of prophylactic vaccines that are to prevent transmission of specific high-risk HPVs. Given, however, that these vaccines have no therapeutic efficacy and HPVassociated cervical cancers arise years if not decades after the initial infection, it has been estimated that there will be no measurable decline of HPV-associated tumors before 2040. Cervical cancer alone will be diagnosed in more than 375,000 US women between now and 2040. Other HPV-associated anogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this time period. Hence, therapeutic efforts to combat high-risk HPV-associated disease remain of critical importance.

Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion

“…Moreover, two prophylactic vaccines based on HPV L1 VLPs have recently been licensed [5,6]. Yet, these vaccines have no therapeutic efficacy and it has been estimated that there will be no measurable decline of HPVassociated tumors before 2040 [7].…”

“…Consequently, most studies aiming to investigate interactions between virus and host cells have used virus-like particles (VLPs), which result from HPV L1 major capsid protein self-assembly and which are morphologically and immunologically [5,6]. Yet, these vaccines have no therapeutic efficacy and it has been estimated that there will be no measurable decline of HPVassociated tumors before 2040 [7].…”

“…Consequently, most studies aiming to investigate interactions between virus and host cells have used virus-like particles (VLPs), which result from HPV L1 major capsid protein self-assembly and which are morphologically and immunologically [5,6]. Yet, these vaccines have no therapeutic efficacy and it has been estimated that there will be no measurable decline of HPVassociated tumors before 2040 [7].HPV infection can be controlled by the host immune response and the vast majority of HPV-infected women clear the virus within two years [8]. Moreover, the prevalence of HPV-induced tumors is higher in immunodeficient patients [9].…”

Chemotherapeutic alteration of β-catenin and c-kit expression by imatinib in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in vitro

“…For the establishment and maintenance of the malignant phenotype the expression of viral oncogenes E6 and E7 are pivotal in human carcinogenesis and in DNA synthesis induction, cell death modulation, cellular life span extension, genomic instability, cytoskeleton changes, alteration of the cellular polarity, as well as induction of pro-angiogenic factors and of the EMT, a process which is important in invasion and metastasis (70,71).…”

Future of Surgery and Shrinking Surgeon

“…Fundamental conceptual changes especially in the biological behaviour of the cancer cells have made drastic changes in oncological care. Cancer vaccines have become the highlight of the day like in cervical cancer [5].…”