Oral Head and Neck Oncology and Reconstructive Surgery is provide readers with a system for managing adult head and neck cancers based
The term head and neck cancer is generally used to describe the range of malignant neoplasms of soft tissue origin that develop in the oral cavity including the lips, nasal cavity, paranasal sinuses, pharynx, larynx, and salivary glands. The skin is included in many descriptions, but not usually ocular and intracranial neoplasms, nor those of endocrine or lymphatic origin—thus excluding thyroid and parathyroid cancers, lymphomas, and sarcomas.
Approximately 90% of head and neck cancers are squamous cell carcinomas (SCCs), which originate from the epithelium of the mucosal lining of the upper aerodigestive tract (UADT), and adenocarcinomas from associated secretory glands. Head and neck squamous cell carcinoma (HNSCC) is strongly associated with environmental and lifestyle risk factors, particularly tobacco use, both smoked and “smokeless”; the chewing of areca nut (i.e., betel nut); regular alcohol consumption, diets poor in antioxidant vitamins and minerals; ultraviolet (UV) light from the sun; indoor and outdoor air pollution; occupational exposures to radiation or chemical carcinogens; and, increasingly, certain viruses, perhaps sexually transmitted – notably “high-risk” genotypes of the human papillomavirus (HPV) family (particularly HPV16 and HPV18, especially when originating in the tonsil, base of tongue, and elsewhere in the oropharynx), and some human herpesviruses (HHVs; Epstein-Barr virus [EBV] with nasopharyngeal carcinoma). There is a modest inherited susceptibility. Chronic trauma and chronic inflammation are reemerging as significant cofactors. Around the world, with the exception of HPV-related cancers, HNSCC is predominantly a disease of the poor; inequalities and contributing factors have been analyzed by Johnson and colleagues.1
HNSCC is known for its capricious biologic behavior and is characterized by local tissue destruction, early and frequent metastasis to the cervical lymph nodes, and a relatively high rate of distant metastases. A large proportion of patients have recurrence of the primary lesion and/or develop a second primary neoplasm, even after effective local therapy. Respiratory and cardiovascular comorbidities are common, usually resulting from tobacco and alcohol abuse and/or poor nutrition.
HPV-associated HNSCC is a distinct clinical and biologic entity that responds much better than HPV-negative carcinomas to conventional therapies. However, HPV-related disease is much less frequent in oral cavity and larynx cancers (<5%) than it is in cancers of the oropharynx (40–80%).2 The prevalence of HPV in oropharyngeal cancers significantly increased in recent years, and the annual number of HPV-positive oropharyngeal cancers will be likely higher than the number of cervical cancers by the year 2020.3,4 Whereas the incidence and survival rates of oropharyngeal cancer are greatly increased because of HPV infection, the majority of patients with oral cavity and laryngeal cancer develop locoregional relapse (56%), and as many as a third (34%) will also develop distant metastases despite technologic improvements in local therapies.5 Indeed, only two biotherapies have been approved by the U.S. Food and Drug Administration (FDA) for HNSCC in the past 10 years: monoclonal antibodies directed at blocking the family of epidermal growth factor receptors (cetuximab) on the surface of malignant keratinocytes, in neoplasms with overexpression of these molecules; and, more recently, an immunotherapy targeting programmed cell death receptor 1 (PD-1), pembrolizumab. New therapeutic strategies for recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC) are thus urgently needed, particularly in the HPV-negative patient.