Prognostic indicators in head and neck oncology including the new 7th edition of the AJCC staging system.

Head and neck squamous cell carcinoma (HNSCC) represents a number of different diseases each with unique clinical “niche” issues. Clinicopathologic or molecular studies based upon small numbers of patients which group together different anatomic sites and stages are not optimized to address these niche issues and are usually destined to have limited clinical impact. An underlying consideration for any investigation is, “Will this biomarker/indicator add prognostic value beyond known clinical confounders?” Will it retain prognostic significance after model building, which should include confounders such as site, stage, gender, age, and treatment, as well as other factors such as the continuation of smoking, race, Human Papillomavirus (HPV) status, and resection margin status? Only biomarkers/indicators that remain significantly associated with outcome after regression analysis have the potential for clinical usefulness. The number of confounders requiring consideration will impact the required cohort size to study any biomarker. It is startling how rarely this issue of sample size is mentioned in publications, and often omitted is the acknowledgment that the lack of statistical significance in small studies does not negate the possibility of a significant association. The goal of this manuscript is to review the recent changes in the 7th edition of the AJCC staging criteria for HNSCC and to focus on some of the validated prognostic indicators for HNSCC. The following focused questions currently facing clinicians will be discussed: Which patients with stage I oral SCC will require elective neck dissection? Which patients with stage I/II oral/oropharyngeal SCC will fail primary surgical therapy? What impact does resection margin status have on outcome? Which oropharyngeal carcinomas are HPV+ driven cancers, and thus may be overtreated by current regimens? The 7th AJCC Staging Criteria: General Issues The recently published 7th AJCC staging criteria [1] contain the following major modifications for head and neck cancers: (1) Staging components for nasopharyngeal carcinoma have shifted (2) Thyroid T1 neoplasia are now subdivided into T1a and T1b, and (3) New staging criteria have been added for mucosal melanoma. A common minor change is the addition of the descriptors “moderately advanced” and “very advanced” to T4a and T4b tumors, respectively, for lip, oral cavity, oropharynx, nasal cavity, laryngeal, major salivary carcinomas and thyroid carcinomas. However, the actual anatomic landmarks defining T4a and T4b for each of these anatomic sites remain the same. Additionally, reporting prognostic factors (“site-specific factors”) is recommended for oral and pharyngeal cancers, although not required for staging. These site-specific factors are related to the primary site, i.e. tumor thickness and HPV status, as well as nodal disease, i.e. node size, location/level, and extracapsular spread. Tumor thickness is germaine to only small T1 SCC, and expressed in millimeters. It is measured perpendicularly from the surface of the invasive SCC to the deepest area of involvement. This indicator measures both the exophytic and invasive tumor components. In distinction, the indicator of tumor depth of invasion is measured from the level of the mucosal surface to the deepest part of the tumor. Depth of invasion is also germaine to only small T1 SCC. With respect to HPV status as a site-specific factor, there are no recommendations as to the specific method for HPV detection. Extracapsular spread has long been recognized as being associated with poorer prognosis, and can be recognized clinically by the presence of a “matted” lymph node mass, fixation to overlying skin, carotid sheath structures, soft tissues, or cranial nerve involvement. Pathologically, extracapsular spread should be classified as either gross (Eg), characterized by tumor apparent to the naked eye beyond the confines of the lymph node capsule, or microsopic (Em), defined as metastatic tumor beyond the lymph node capsule, associated with desmoplasia. No extracapsular spread should be designated as En. The reporting of the following features is also recommended: (1) Histological grade, (although subjectivity is acknowledged), (2) Vascular invasion and (3) Perineural invasion. Changes in Staging for Nasopharyngeal Carcinoma The staging criteria for nasopharyngeal carcinoma (NPC) has become more consolidated. Tumors previously classified as T2a (extension to oropharynx and nasal cavity without parapharyngeal extension) are now classified as T1; consequently, Stage IIA NPC is now Stage I. Tumors previously classified as T2b (parapharyngeal extension—beyond pharyngobailar fascia) are now classified as T2 and Stage IIB NPC is now Stage II. Lastly, bilateral retropharyngeal lymph node metastases, previously classified as N2, are now classified as N1 (Table 1). Histologically, NPC is classified according to the latest WHO criteria (keratinizing, nonkeratinizing, and basaloid). This replaces the previous terminology of WHO I (keratinizing carcinoma), WHO II (transitional cell carcinoma) and WHO III (undifferentiated or lymphoepithelial carcinoma). Table 1 AJCC staging criteria for nasopharyngeal carcinoma Changes in Staging for Thyroid Carcinoma For thyroid neoplasia, T1 tumors are now staged as either T1a (≤1 cm) or T1b (>1–2 cm), but the TNM staging groups are not affected. The most significant staging modifier for well-differentiated thyroid cancer (papillary and follicular carcinomas) remains patient age. Patients under 45 with well-differentiated thyroid cancer, any T, any N, and M0 have Stage I disease; while those patients with distant metastases (M1) are classified as Stage II. Patients 45 years of age or older are classified either as Stage I, II, III, or IV by other grouping definitions. Finally, descriptors of solitary (s) versus multifocal (m) tumor have been added to the pathologic staging.