Current Cancer Therapy Reviews - Volume 11, Issue 1, 2015

Human papilloma virus (HPV)-associated oropharyngeal carcinoma (HPV-OPC) is increasing in many countries. It has distinct microscopic and molecular features as well as clinical aspects. As for microscopic view, two subtypes, non-keratinizing squamous cell carcinoma (NKSCC) and hybrid SCC (HSCC), 3 variants of SCC, undifferentiated carcinoma (UC), basaloid carcinoma (BC), and papillary squamous cell carcinoma (PSCC), and 2 histological structures, abrupt keratinizarion and comedo-necrosis among non-maturing island are related with HPV-OPC. As for molecular aspects, HPV-OPC is more likely to have p53 degradation and Rb (retinoblastoma protein) inactivation with resulting p16 up-regulation compared to HPV-unassociated oropharyngeal carcinoma.

The basic anatomical and oncological properties of oropharyngeal cancer with appropriate radiological images are presented. The description is mainly divided into two categories; primary lesion and metastatic lymph nodes. Each of the categories is discussed in terms of the anatomy, oncology and current radiological imaging with emerging methods, such as FDG PET/CT and MRI diffusion imaging. Some interesting cases of lymphatic metastasis are also presented. A brief description on post-treatment observation of the disease is also given.

Due to the progressive decline in smoking and drinking, incidences of head and neck cancers have decreased markedly in the USA and European countries. However, incidences of oropharyngeal cancer (OPC) are rising worldwide in both nonsmokers and nondrinkers. Epidemiologic studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. While HPV-associated oropharyngeal carcinoma is characterized by locally advanced disease and poorly differentiated histology, HPV-associated OPC is identified with effective prognosis by reason of its positive response to chemotherapy and radiation. Nevertheless, clinicians need to be aware of the risk of OPC in young people in order to avoid unnecessary delays in diagnosis and treatment. Interviews with attention to obtaining information including the patient’s history of oral sex can aid in establishing a precise diagnoses in young patients with enlarged neck nodes and/or tonsillar masses.

In a recent years, oropharyngeal carcinoma has continued to gradually increase throughout the world due to the prevalence of Human papillomavirus(HPV)-associated oropharyngeal carcinoma.Traditionally, the standard form of treatment employed was an open surgical procedure combining mandibulectomy with a free flap graft. However, many reports indicate that this procedure can result in a high degree of postoperative morbidities and poor quality of life when compared with transoral surgery. Furthermore, transoral surgery is a minimally invasive technique which has demonstrated excellent oncologic, aesthetic and functional outcomes. In view of the fact that radiation therapy is regarded as being a relatively effective treatment for HPVassociated oropharyngeal carcinoma, it is a standard procedure for concurrent chemoradiotherapy to be employed in order to increase organ-preservation. However, radiation oncologists have reported severe complications such as dysphagia. At the present time, effective management of this disease has not been established and therefore remains controversial. In this chapter, we describe the present status of transoral resection, and advantages and disadvantages of transoral surgery when compared with available other surgical procedures and chemoradiotherapy.

Transoral Robotic Surgery (TORS) was reported as being one of the most minimally invasive surgery (MIS) procedures available by the University of Pennsylvania in 2005. TORS has increasingly been employed in the treatment of oropharyngeal carcinoma throughout the world on account of the various advantages including superior surgical manipulation of the oropharyngeal tissue, excellent visualization and accurate resection. We investigated 16 cases relating to TORS and oropharyngeal carcinoma from a total of 78 English academic documents. We analyzed data from 595 patients who were treated with TORS from 2005 to 2013. Patient numbers of T1, T2, T3 and T4 were 243, 296, 38 and 18, respectively. The number of N0, N1, N2 and N3 were 168, 98,307 and 22, respectively. The mean hospital stay time was 5.3 days. In regard to margin status, the margin free rate was 93.1%. The percutaneous gastrostomy (PEG) tube dependency rate was 3.8%. Loco-regional recurrences and distant metastasis were reported at 3.0% and 2.8%, respectively. The two year overall survival rate was 80.6-100%, and 2 year disease free survival rate was 92-100%. We conclude that TORS is a safe and advantageous procedure for treating oropharyngeal carcinoma.

In recent years, cases of HPV-positive oropharyngeal carcinomas (HPVOPCs) have continued to increase throughout world. In many cases, radiotherapy is conducted as HPVOPCs are considered to be more radiosensitive than HPV-negative tumors. However, smoking affects the radiosensitivity of HPVOPCs which typically results in a poorer prognosis than can be expected when treating HPVOPCs associated with non-smokers. Prior to radiotherapy, it is critical that patients HPV status, neck metastasis, and history of tobacco use are examined carefully. In regard to locoregionally advanced OPC (T3-4, N2-3, Mx), the optimal treatment is considered to be concurrent chemoradiotherapy. Multiple studies have reported that concurrent chemoradiotherapy improves locoregional control and overall survival in patients with locoregionally advanced head and neck cancer. However, significant acute and late toxicities of concurrent chemoradiotherapy have been recorded in up to 29% of survivors. Consequently, patients require gastrostomy tubes and there have been unexplained cases of late mortality. As a result, clinical trials examining deintensification treatment are currently investigating new strategies to improve patient prognosis associated with HPVOPC. However, regional relapses of advanced OPC were significantly poor prognosis. It is imperative that the indication of deintensification treatment for OPCs be carefully considered due to the current low salvage rate.

The controversial point of treatment for oropharyngeal cancer is the surgical approach and it is in transition, especially for resectable tumors. Transcervical oropharyngectomy with mandibulotomy is an oncologically valid surgical option for resectable T3–T4a oropharyngeal cancers and contraindications for transoral lateral oropharyngectomy. The approach without mandibulotomy allows for simple reconstruction and has a low complication rate. In particular, it spares the patients’ morbidity related to mandibulotomy. The transoral approach, especially with robotic surgical systems seem likely to offer an alternative approach and refinement of oropharuyngectomy in the future.

Glioblastoma is the most common adult malignant primary brain tumor, and carries a dismal prognosis. After initial standard radiation therapy and chemotherapy with temozolomide, few standard chemotherapy options are available. In the last two decades, a growing understanding of molecular pathogenesis of glioblastoma has turned our focus toward targeted therapy. This review will discuss our current understanding of gliomagenesis and highlight the clinical attempts to manipulate these vital pathways, describing past and current studies, and future directions.

Oncogenic transformation of growth factors, growth factor receptors, transcription factors as well as important cellular proteins and their association with the principal tumor suppressor p53 may provide essential insights toward integrated therapy in breast cancer. In this review we discuss growth factor HER-2/neu receptor tyrosine kinase; FAK, non-receptor tyrosine kinase; TGF-β, and their roles in tumorigenesis in breast cell with respect to p53. VEGF is a powerful angiogenic factor and its expression is also regulated by p53. E3 ligases like MDM2 and cullin 7 are considered as oncoproteins and they interact differently with p53 in breast cells. Aberrant expression of these ligases is associated with tumorigenesis. The transcription factor cyclin E is involved in cell cycle progression while its activity is subjected to p53 regulation through p21. The necrosis factor NF-κB regulates p53 expression by binding to its promoter and modulates expression of anti-apoptotic protein survivin in breast cancer cell. Apoptosis by Bcl-2 family of protein is largely dependent upon the balance of pro-apoptotic and anti-apoptotic protein expression regulated by p53. In essence, the complexities of p53 interactions with various types of oncogene products require close exploration towards an integrated therapy against breast cancer.