Introduction
The tumor, node, metastasis (TNM) staging system allows clinicians to categorize tumors of the head and neck region in a specific mannerto assist with the assessment of disease status, prognosis, and management. All available clinical information may be used in staging: physical exam, radiographic, intraoperative, and pathologic findings, Other than histopathologic analysis, biomarkers and molecular studies are not yet included in the staging of head and neck cancers. Three categories comprise the system:
T- the characteristics of the tumor at the primary site
(this may be based on size, location, or both);
N- the degree of regional lymph node involvement; and
M- the absence or presence of distant metastases.
The specific TNM status of each patient is then tabulated to give a numerical status of Stage I, II, III, or IV. Specific subdivisions may exist for each stage and may be denoted with an a, b, or c status. In general, early-stage disease is denoted as Stage I or II disease, and advanced-stage disease as Stage III or IV disease. Of importance is that any positive metastatic disease to the neck will classify the disease as advanced, except in select nasopharynx and thyroid cancers.
A. Upper aerodigestive tract sites
The majority of tumors arising in the head and neck (other than nonmelanoma skin cancers) arise from the squamous mucosa that lines the upper aerodigestive tract (UADT) and are predominately squamous cell carcinomas. The UADT begins where the skin meets the mucosa at the nasal vestibule and the vermillion borders of the lips and continues to the junction of the cricoid cartilage and the cervical trachea and at the level of the cricoid where the hypopharynx meets the cervical esophagus. The UADT is organized into several major sites that are subdivided to several anatomic subsites. The major sites include (1) the oral cavity, (2) the oropharynx, (3) the hypopharynx, (4) the larynx, (5), the nasopharynx, (6) and the nose and paranasal sinuses.
1. Oral Cavity
The oral cavity is a common site for squamous cell cancers of the UADT, probably because it is the first entry point for many carcinogens. The anterior aspect of the oral cavity is the contact point of the skin with the vermilion of the lips extending posteriorly to the junction of the hard and soft palates, and with the anterior tonsillar pillars and the circumvallate papillae forming the posterior limits. The major subsites of the oral cavity are the lips, anterior tongue, floor of mouth, buccal mucosa, upper and lower alveolar ridges, hard palate, and retromolar trigone. The trigone consists of the mucosa overlying the anterior aspect of the ascending ramus of the mandible. Tumors of the oral cavity tend to spread regionally to lymph nodes of the submandibular region (Level I) and to the upper and middle jugular chain lymph nodes (Levels II and III). Because of accessibility and the risk of involvement of bony structures, treatment with radiotherapy can lead to radionecrosis of the mandible or maxilla. Moreover, oral cavity squamous cell carcinomas may be less sensitive to chemotherapy and radiation, relative to oropharyngeal or laryngeal cancers. Thus, primary treatment for most tumors is surgical. Positive surgical margins, multiple involved lymph nodes, and/or extracapsular tumor extension call for consideration of postoperative chemoradiotherapy, to improve local disease control.
2. Oropharynx
This structure begins where the oral cavity ends at the junction of the hard and soft palates superiorly and the circumvallate papillae inferiorly and extends from the level of the soft palate superiorly, which separates it from the nasopharynx and to the level of the hyoid bone inferiorly, where the hypopharynx begins. The subsites of the oropharynx are the tonsil, base of tongue, soft palate, and pharyngeal walls. Cancers of the oropharynx often metastasize to upper and middle jugular chain lymph nodes (Levels II and III), but can also spread to retropharyngeal lymph nodes, which distinguishes them from oral cavity tumors and must be considered when treating oropharyngeal cancers. Tumors in this site are generally treated with radiotherapy, as a single modality for T 1/2 or N 0/1 stages. Increasingly, some of these cancers are associated with human papilloma virus 16 infection, especially in nonsmokers. However, for patients with more advanced disease, T 3/4 or N 2 b/c/3 staging, chemoradiotherapy most often with a concomitant approach has become standard. Cisplatin, administered during weeks 1, 4, and 7 has most often been studied and may be considered a standard. Nonetheless, other regimens, carboplatin, taxanes, and drug combinations, such as cisplatin or carboplatin with fluorouracil, are also reported. Induction chemotherapy before radiotherapy (or chemoradiotherapy) remains an investigational strategy.
3. Hypopharynx
The hypopharynx has its superior limit at the hyoid bone, where it is contiguous with the oropharynx and it extends inferiorly to the cricopharyngeus muscle, where it meets the cervical esophagus. The major subsites of the hypopharynx are the pyriform sinuses, the postcricoid region, and the pharyngeal walls. Tumors often present here at advanced stages and can be difficult to cure, and because of their location can impact swallowing and speech function adversely. Spread to the upper,middle, and lower jugular lymph nodes (Levels II–IV) and the retropharyngeal nodes is common in these cancers. Two other hallmarks of hypopharyngeal cancers are submucosal spread and skip areas of spread. Surgery had been themainstay of primary treatment for hypopharyngeal cancers formany years, but increasingly radiotherapy and chemoradiotherapy are used to treat cancers in this location with success.
4. Larynx
The larynx is the most complex of the mucosal lined structures of the UADT. Its important roles in speech, swallowing, and airway protection make the treatment considerations of cancers of this structure varied and controversial. The larynx is bordered by the oropharynx superiorly, the trachea inferiorly, and the hypopharynx laterally and posteriorly. The larynx is comprised of a cartilaginous framework, and is subdivided vertically by the vocal cords into the supraglottic, glottic, and subglottic subsites. The supraglottic larynx includes the epiglottis, which has both lingual and laryngeal surfaces, the false vocal cords, the arytenoids cartilages, and the aryepiglottic folds. Anterior to the supraglottis is the pre-epiglottic space. This is a complex space with a rich lymphatic network that contributes to the early and bilateral spread of tumors that arise from supraglottic structures to upper, middle, and lower jugular chain lymph nodes.
The glottic larynx describes the true vocal cords, and where they come together anteriorly at the anterior commissure, as well as where they meet the mobile laryngeal cartilages at the posterior commissure. The glottic larynx extends from the ventricle to 1 cm below the level of the true cords. The vocal cords are lined with stratified squamous epithelia, which contrasts with the pseudostratified ciliated respiratory mucosa lining the remainder of the larynx. Glottic laryngeal cancers tend to metastasize unilaterally and spread regionally less commonly than supraglottic tumors do. Between the thyroid cartilage and the vocal cord lies the paraglottic space, which is continuous with the pre-epiglottic space. This serves as a pathway for submucosal spread of tumors from the glottis to the supraglottis, or vice versa, which is known as transglottic spread. The subglottic larynx starts 1 cm below the vocal folds and continues to the inferior aspect of the cricoid cartilage.While it is rare for tumors to arise initially in the subglottis, tumors arising in the supraglottic or glottis larynx commonly spread in a “transglottic” fashion to involve the subglottic larynx. Subglottic tumors tend to metastasize to paratracheal (Level VI) as well as middle or lower jugular lymph (Levels III and IV) node groups.
Treatment of laryngeal cancers varies widely from center to center, and for early-stage lesions radiotherapy or transoral endoscopic excision are the most common treatment options. Both yield excellent tumor control, but proponents of each modality often disagree on the functional sequelae of the two types of treatment. However, good long-term functional data are lacking. Treatment of more advanced tumors can be even more controversial, but while total laryngectomy was long held as the gold standard for treating T3 and T4 larynx cancers, chemoradiotherapy has been shown to be quite effective in achieving local regional control, survival, and organ preservation. Concomitant chemoradiotherapy may be most appropriate for T3 primary lesions. Treatment of both sides of the neck must be taken into consideration when treating supra- and subglottic tumors, and unilateral neck treatment is considered for patients with advanced glottic tumors.
5. Nasopharynx
The nasopharynx is a cuboidal structure bounded anteriorly by the choanae at the back of the nose where pseudostratified ciliated columnar cells are found. The roof and posterior walls of the nasopharynx are made up of the sphenoid bone and the upper cervical vertebrae, covered with a stratified squamous epithelial lining. Inferiorly, at the level of the soft palate, the nasopharynx meets the superior oropharynx. The opening of the Eustachian tube is found at the posterior-superior aspect of either lateral nasopharyngeal wall; therefore, impingement of this opening by a nasopharyngeal tumor can lead to Eustachian dysfunction manifested by a middle-ear effusion and hearing loss. Thus, all adult patients with an unexplained unilateral middle-ear effusion, particularly in areas where nasopharyngeal carcinoma is endemic (such as southern China, northern Africa, and Greenland), should have their nasopharynx examined. The adenoids, consisting of mucosa-covered lymphoid tissue, are found posteriorly and superiorly in the nasopharynx and are more prominent in children than adults.
While minor salivary tumors can occur in the nasopharynx, most nasopharyngeal cancers are derived from the mucosal lining and fit into one of the three histologic subtypes described by the World Health Organization (WHO). WHO Type I nasopharyngeal carcinoma (NPC) is keratinizing squamous carcinoma, andWHO Type II is nonkeratinizing squamous cell carcinoma.WHO Type III is an undifferentiated tumor, also known as lymphoepithelioma. The Epstein- Barr virus is thought to play a pathogenic role in the development of Type II and III tumors. Nasopharyngeal carcinoma may also metastasize to retropharyngeal and parapharyngeal lymph nodes, as well as lymph nodes along the upper, lower, and middle jugular (Levels II–IV) chains and the posterior triangle of the neck (Level V). Earlystage
NPC is most often treated with radiotherapy alone, and in more advanced cases, T 3/4 N +/ concomitant chemotherapy is being increasingly utilized. Surgery is rarely used in salvage situations at the primary site or neck.
6. Nasal Cavity and Paranasal Sinuses
The paranasal sinuses consist of the paired maxillary sinuses, the superior frontal sinuses, the bilateral ethmoid system, and the central spenoids. This region includes the lining of the nasal cavity (medial maxillary walls) as well as the nasal septum. The majority of sinonasal carcinomas arise in the maxillary sinuses and are most commonly squamous cell carcinomas, although adenocarcinomas are described, especially in woodworkers. Because of inherent bone involvement, initial treatment is usually surgical, with consideration for adjuvant radiation therapy based upon stage and pathologic findings. Reconstruction and rehabilitation, especially in cases with orbital involvement, may be prosthetic or tissue based. Sinonasal carcinomas of the anterior skull base include a variety of pathologies.
Standard treatment is multidisciplinary, including craniofacial surgical intervention with adjuvant radiation and chemotherapy. B. Radiation Therapy and Chemotherapy
External beam radiation therapy (RT) alone or in conjunction with chemotherapy has a well-established role in the treatment of head and neck cancer as definitive therapy or as adjuvant to primary surgical treatment. The last two decades have seen tremendous technological developments in targeting and delivery of RT in a complex treatment site such as the head and neck. Three-dimensional (3-D) conformal RT marked a significant improvement over the conventional two-dimensional 3-field setup in better delineation of tumor volume and nodal volume. This improvement allows limited dosing to normal tissue, while adequately treating the tumor. However, 3-D conformal planning does not always result in optimal shielding ofcritical normal tissues (e.g., salivary glands and visual apparatus), due to current beam constraints.
Intensity-modulated radiation therapy (IMRT) allows for better sparing of such critical normal tissues by modulating the radiation beam in multiple small beamlets, while at the same time adequately covering the tumor volume. With the advent of IMRT, it is also very important for the clinician to be acutely aware of radiologic anatomy (levels of nodal disease, pathways of loco-regional spread of tumor, and delineation of postoperative tumor bed), while utilizing computed tomography, scan magnetic resonance imaging, and positron emission tomography scan for treatment planning. Preoperative clinical and radiologic evaluation of disease is extremely important for postoperative radiotherapy planning, as tissue planes may be obscured after surgery. Such evaluation is also valuable in determining whether ipsilateral or bilateral neck disease needs to be addressed based on tumor location, extent, and size; initial nodal presentation; and likelihood of contralateral nodal involvement.
Certain primary tumor sites have a high risk of retropharyngeal nodal involvement (nasopharynx, piriform sinus, and tongue base), and these nodal groups should be covered in RT target volumes for these tumors. Approximately 20% of anterior tongue and floor of mouth cancers may have skip nodal metastasis to Level IV nodal region, and should be included in RT volumes.
Important considerations in RT planning following surgical resection include a thorough evaluation of the surgical pathology report with respect to resection margins, extension to soft tissue/bone, and perineural or lympho-vascular invasion at the primary site and size; extra-capsular extension (ECE); and the number and level of nodal involvement. Postoperative patients with ECE are at high risk for loco-regional recurrence. Careful adjuvant treatment planning includes consideration of radiation dose (60–66 Gy), addition of concurrent chemotherapy (RTOG 95-01), extension of the RT clinical target volume to include overlying skin, and elective irradiation of contralateral neck nodes. The clinical target volume in radiation therapy of a clinically or pathologically involved neck typically extends up to the skull base to treat the highest neck nodes. In the contralateral elective neck irradiation, the highest treated nodes are jugulodigastric nodes.
Adjuvant RT should ideally begin within 4–6 weeks following primary surgical resection and neck dissection, unless postoperative complications significantly delay wound healing. Delaying adjuvant therapy has been shown to significantly decrease loco-regional control.
 |
| American Joint committee on cancer (AJCC)-Tumour staging by site |
 |
| AJCC tumour staging-Nasopharynx and thyroid |
Hairy leukoplakia - This variety of leukoplakia was first recognized in HIV-infected patients but has been encountered in other immune deficiency states such as organ transplant patients who are intentionally immune suppressed. The lateral tongue is the most common location (Fig. 4). Lesions are of rough texture, adherent and asymptomatic. The diagnosis of hairy leukoplakia can be suspected on routine biopsy specimens, but confirmation requires demonstration of the presence of the causative virus, the Epstein-Barr herpesvirus. This is ordinarily achieved by DNA in situ hybridization. A word of caution: hairy leukoplakia may be confused with candidiasis. A patient who presents with a white lesion should be treated with antifungal therapy first. If it fails to heal, it most likely is hairy leukoplakia. 
