Head and neck cancers are primarily squamous cell carcinomas that arise from the mucosal epithelial cells of the head and neck. They include tumors of the paranasal sinuses, nasopharynx, oropharynx, hy-popharynx, larynx and the oral cavity. A variety of immunological abnormalities occur in tumors and may be important prognostically. Both cell-mediated and humoral immunity is altered in cancers, although attention has been more focused on the humoral immune system in mucosal tumors of the head and neck.
The annual number of new cases diagnosed in the US is approximately 40,000, accounting for about 5% of the malignancies in the adult population . There are geographic variations in the location of head and neck cancers. In the Far East and Mediterranean countries, nasopharyngeal carcinomas are more common, whereas oral, oropharyngeal and laryngeal carcinomas comprise most of the head and neck cancers in Europe and North Americas. Alcohol and tobacco are the most common and significant carcinogens associated with head and neck cancer and the combination of the two carcinogens poses the most potent risk. Other implicated etiological factors include nickel refining, textile fibers, wood working and possibly dietary factors such as lack of fiber and increased consumption of salted fish. A viral etiology has been extensively studied and seems to be important in nasopharyngeal, laryngeal and perhaps tonsillar carcinomas. High levels of the Epstein-Barr Virus antibodies are seen in nasopharyngeal carcinomas in the Mediterranean countries and Far East, and EB V DNA is present in tissue samples of both premalignant lesions and malignant nasopharyngeal carcinomas. Human papilloma virus (HPV) DNA has also been detected in tissue samples of laryngeal and tonsillar cancers.
High IgA levels have been reported in many malignancies and have been studied as potential diagnostic and prognostic markers. The earliest reports of abnormalities in the concentration of IgA associated with head and neck cancer were in 1975 . In the ensuing 6 years, multiple studies reported increases in IgA with head and neck cancer (Table 1). Brown et al.  initially reported increased IgA levels in the saliva and serum of patients with oral and laryngeal cancer and the association of the IgA level with the progression of the disease. They also noted that the serum IgA levels persisted after 'cure' but that salivary levels returned to normal. The salivary IgA levels spiked again on recurrence of the cancer.
Henle et al. [48, 49] found that 93% of sera from patients with nasopharyngeal carcinoma were positive for IgA antibodies to EBV viral capsid antigen (VCA) and 73% to D component of the Early Antigen (EA) complex. Veltri et al.  also studied the cellular and humoral immune status of patients with head and neck cancer and found that total complement, a-1 acid glycoprotein (AGP), circulating immune complexes (CIC) and IgA levels were significantly elevated, pre-treatment, in these patients. The AGP and CIC declined to nearly normal levels after treatment, but the IgA levels remained elevated. They also studied cell-mediated immunity (CMI) in these patients using both polyclonal activators and specific antigens and found significant depression of CMI both pre- and post-treatment. Similarly, Hollyfield et al.  studied salivary IgA levels in alcoholics and head and neck cancer patients and found significantly higher levels of IgA in the cancer patients.
Vinzenz et al.  measured the serum IgG, IgM, IgA and IgE levels in 226 patients with head and neck cancer before therapy. The IgA and IgE levels were significantly elevated in these patients compared to controls, whereas the IgG and IgM levels were not significantly different. On follow-up of more than 6 months the patients with recurrence of the disease had significantly higher IgA and IgE levels than those without recurrence.
Susal et al.  studied the association of serum IgA-anti-Fab antibody levels with disease stage in 101 patients with squamous cell cancer of the head and neck and 8 patients with adenoid cystic carcinoma. They found significantly higher levels of these autoantibodies in the cancer patients compared to controls. Circulating immune complexes have also been studied in relation to cancer and seem to correlate with tumor burden and overall poor prognosis [54-56], Das et al.  estimated circulating immune complexes (CIC) in 31 patients with head and neck cancer and 25 controls. All patients with cancer had high levels of CIC, which correlated with stage and survival. None of the controls were positive.
Baseler et al.  studied the immune complexed IgA in a heterogenous group of patients with head and neck cancer, nasopharyngeal, colon and lung cancer. They compared the levels to a group of healthy blood donors and a group of benign surgery patients.
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