Recent Progress in Therapeutic Treatments and Screening Strategies for the Prevention and Treatment of HPV-Associated Head and Neck Cancer

Abstract

The rise in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has elicited significant interest in the role of high-risk HPV in tumorigenesis. Because patients with HPV-positive HNSCC have better prognoses than do their HPV-negative counterparts, current therapeutic strategies for HPV+ HNSCC are increasingly considered to be overly aggressive, highlighting a need for customized treatment guidelines for this cohort. Additional issues include the unmet need for a reliable screening strategy for HNSCC, as well as the ongoing assessment of the efficacy of prophylactic vaccines for the prevention of HPV infections in the head and neck regions. This review also outlines a number of emerging prospects for therapeutic vaccines, as well as for targeted, molecular-based therapies for HPV-associated head and neck cancers. Overall, the future for developing novel and effective therapeutic agents for HPV-associated head and neck tumors is promising; continued progress is critical in order to meet the challenges posed by the growing epidemic.

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

“…They primary source (41% of cases) is the oral cavity, but they are also often found in the pharynx and larynx, (22 and 24% of cases, respectively) (2). The majority of patients with HNSCC are clinically identified prior to metastasis, and therefore are potentially able to be cured by an aggressive therapy regimen, comprising surgery, chemotherapy and/or radiotherapy (3). Nevertheless, despite recent improvements to utilized surgical techniques, chemotherapy and radiation delivery, and supportive care, which have improved the quality of life of patients, the HNSCC disease recurrence rate remains unacceptably high, occurring in up to 50% of patients within the first 2 years of diagnosis (4,5).…”

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer

“…In contrast to HPV-positive HNSCC patients, which have a more favorable prognosis (3,4), patients with HPV-negative HNSCC have a poor prognosis, with more than half of the patients developing recurrent or metastatic diseases (5). Recently, checkpoint inhibitors, such as mAbs against programmed death-1 receptor (PD-1) and its ligand (PD-L1), have shown promising therapeutic efficacy in both HPV-positive and -negative HNSCC (6)(7)(8).…”

An Update on Cellular MicroRNA Expression in Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma

“…HPV-associated tumours tend to occur in young (< 60 years age), male, Caucasian patients, typically with a higher level of education and income, as well as improved functional status [2,5,7,8]. This cohort of patients tends to present at an earlier T-stage, and a more advanced N-stage at diagnosis; and several large trials have demonstrated an improved responsiveness to chemotherapy and radiotherapy primarily, as well as an overall improved survival rate [5,7,8].…”

“…HPV are non-enveloped, double-stranded DNA viruses of the Papillomaviridae family, with a genome of approximately 8,000 bp [2,12]. The mucosal HPV genome encodes 6 early proteins (E1-2 and E4-7) and 2 late structural proteins (L1, L2), and a non-coding control region [11].…”

“…They are transmitted through mucosal and skin epithelium via small tears, which allow the virus access to the basal layer of the epithelium. HPV requires cell-cycle progression for completion of its lifecycle, and therefore takes advantage of the cell differentiation between basal and upper layers of epithelium [2,12]. HPVs are grouped into high-risk types (HPV-16, 18, 31, 33 etc), and low-risk types (HPV-6, 11 etc) based on their demonstrated oncogenic potential (particularly of E6 and E7 oncoproteins, which have effects on the p53 and pRB cellular pathways respectively) [11].…”