HPV infection has now been recognized as an important risk factor for a subset of HNSCC, particularly those arising from the oropharynx (base of tongue and tonsils). HPV-16 and HPV-18 represent the most prevalent viral types, and they show specific virus-tissue interactions in HNSCC. In addi- tion, patients with HPV-positive HNSCC seem to have a bet- ter overall and disease-specific survival, as compared with the HPV-negative group. On the other hand, EBV has critical viral transforming functions in epithelial cells that may lead to the development of NPC, as evidenced by the consistent expression of EBV viral genes and latent membrane proteins in NPC. The tumorigenic activities of HPV in HNSCC and EBV in NPC have been well studied and documented, but there is a glaring lack of evidence regarding the interaction of HPV or EBV with precancerous lesions.
Early diagnosis of virus-associated cancers is vital in combating the diseases, as it is much more effective when the tumors are treated at the early stage before metastatic spread. However, a positive detection of viral infection does not necessarily mean the development of cancer. In this regard, it is also important to develop new molecular bio- markers, in addition to viral DNA and proteins, for a more precise diagnosis of HPV- or EBV-associated HNSCC.
Prophylactic vaccines have the potential to prevent and treat virus-associated HNC. However, it is equally important to develop molecular targeted therapies for patients with the cancers so as to slow down the progression of transformed cells and improve the survival.
The mechanism of virus-associated tumorigenesis is complex, involving the aberrations of many signaling path- ways and the alteration in expression of numerous proteins leading to immune escape by malignant cells. Although clin- ical studies have shown strong association between HPV/
EBV and subsets of HNCs, the molecular mechanism regarding how these viruses facilitate the development of HNC remains largely unclear. Previous molecular studies on HPV-associated HNCs have focused on DNA and chromosomal
levels, but few on transcriptomic and proteomic profiles [29, 102]. An improved mechanistic understanding of the virologic basis for HNCs would require profound analysis of these tumors using high-content molecular analysis technol- ogies (e.g., proteomics). This would facilitate the develop- ment of targeted therapies for treatment of these cancers if immune escape can be reversed. Meanwhile, molecular clas- sification of tumors is likely to provide important transla- tional information that will allow a better estimate of prognosis and may well influence treatment decisions if future HPV- stratified clinical trials support this approach.
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J. Bernier (ed.), Head and Neck Cancer: Multimodality Management, 135
DOI 10.1007/978-1-4419-9464-6_8, © Springer Science+Business Media, LLC 2011
Abstract The prognosis of head and neck cancer embodies numerous dimensions of outcome governed by a large array of factors within the patient and the tumor. These can be influenced by external factors that include access to an ade- quate standard of treatment for these tumors. For many out- comes, especially the key end-points of organ preservation, loco-regional control, occurrence of distant metastases, and survival, anatomic extent of disease remains one of the most powerful prognostic factors. This is embodied in the tumor- node-metastasis (TNM) classification which has provided a very effective enabling tool to facilitate many elements of cancer control. Traditionally, its contribution has been a codified classification and language to describe anatomic stage of disease for use in the clinic, determining eligibility and stratification for clinical trials and treatment protocols, and for comparison and surveillance of treatment results among centers and jurisdictions. More recently, a focus on nonanatomic factors has become very important, partly because it is recognized that traditional extent of disease does not embrace all dimensions of prognosis. In particular, this relates to the quest to understand the biological dimensions of cancer that are needed to achieve more personalized and/
or biologically driven therapies. Increasingly, there is a need in head and neck cancer to exploit new biological discover- ies to permit modification of treatment and interventions in the clinic for this heterogeneous group of tumors. Because of this, the TNM has been criticized due to a perception that it has not been adapted sufficiently to modern needs despite its worldwide adoption. This may stem from the fact that there is no alternative uniform functional framework available to classify nonanatomical predictive and prognostic factors.
There seems to be a tendency to regard TNM as the optimal receptacle for these factors due to its uniform appeal and success. As the field evolves, both anatomic disease extent and other factors, especially those addressing biological
behavior of disease, need to be studied in their component domains as well as in combination using an agreed enabling taxonomy. An important strategy is to move toward construct- ing prognostic models, likely using prognostic nomograms, which will not only include the TNM staging information, but will also include other parameters of prognosis including comorbidities and biochemical or genetic markers. In addi- tion, experts in one area (e.g., translational science or clinical trials methodology perhaps) who may rely on TNM may not always consider that the classification provides very different needs for others (e.g., health services research or screening and cancer control initiatives, etc.) and vice versa. Ignoring or dismissing one dimension of prognosis compared to another will not be fruitful and the true contribution of each will remain unappreciated, and the goals of the prognostic factor effort in head and neck cancer may be left unfulfilled.
Keywords Head and neck cancer • Staging • Prognosis
• Prognostic models
Introduction
In oncology, “to stage” a patient implies two intentions. The first uses clinical examination and investigations to describe the extent of disease to permit a rational treatment strategy to be formulated. The second employs an agreed classification system to categorize the extent of disease within risk hier- archies that predict the outcome following conventional treatment strategies. For the latter, the foremost priority is given to the risk of death and is provided by the joint primary tumor-node-metastasis (TNM) classification of the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), a discussion about which will comprise much of this chapter. A challenge is to also consider new methods to enhance prognostic infor- mation and determine if these can be incorporated into or complement the traditional anatomically based classification.
A variety of candidate areas exist and include features relevant to the host (or patient), the environment of the patient’s
B. O’Sullivan (*)
Head and Neck Oncology Program, Department of Radiation Oncology, Princess Margaret Hospital,
610 University Avenue, Toronto, Ontario, M5G 2M9, Canada e-mail: [email protected]