# Background
Head and neck cancer includes a variety of tumours that originate in the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid, and salivary glands. Worldwide, it represents the 6th most common type of cancer and accounts for about 6% of all cancers. Smoking, alcohol, age and sex are some of the most common factors for the development of head and neck cancer 1 .
Head and neck cancers are considered among the most complex types of cancers where treatment decisions are made by a multidisciplinary team which includes both oncologists and allied health care professionals such as dietitians, dentists, and speech-language pathologists 2 . The initial evaluation of patient tumour is the most critical step for treating the cancer; it provides information that is essential to making decision on optimal treatment plans. The initial assessment includes indirect mirror and direct endoscopy however the advanced assessment is done by imaging and biopsies. Imaging tools (CT, MRI, PET or PET/CT) are important for determining the local infiltration, regional spread, distant metastases or second primary tumours.
The purpose of this guideline is to outline the diagnosis, and staging recommendations for patients with head and neck cancer in Alberta. 

# Search Strategy
The National Guideline Clearinghouse and individual cancer agencies' websites were searched for clinical practice guidelines related to Workup and staging for Head and Neck cancer. A systematic literature review was performed by using the Pubmed, EMBASE, and MEDLINE databases. The detailed literature search strategy is outlined in Appendix A, and the evidence tables are available upon request.

# Target Population
The recommendations outlined in this guideline are intended for adults over the age of 18 years with suspected malignancies arising in the mucosal surfaces of the upper aerodigestive tract, including the oral cavity, pharynx, larynx, and paranasal sinuses. Different principles may apply to pediatric patients or patients with thyroid/salivary gland pathology.

# Recommendations
The following recommendations should be applied in the context of the recommendations outlined in the Alberta Health Services guideline, ' 3. Inquire about HPV vaccination history.

# Physical Exam:
- Physical examination should include: inspection of the neck for lymph nodes, inspection of the facial and scalp skin; inspection of the oral cavity for ulceration of mucosa, swellings, and red or white patches and inspection of the anterior nasal cavities.

# Referral to Specialist:
- For ulcerative lesions or masses that are initially treated as potential infections, or bleeding nasal lesions that are treated with moisturizing ointments and humidification, establish time limit for followup to ensure early referral for specialty care (i.e. if lesion is not resolved or dramatically improved after 3 weeks of therapy, refer for urgent specialty review).

# II.
Workup at Cancer Centre General 6. Once biopsy proven head and neck cancer identified, newly diagnosed cases should be referred to an appropriate head and neck oncologist (with affiliations to a regional cancer centre) to develop an appropriate treatment plan as soon as possible.
- All patients should undergo tumour classification and staging prior to treatment. Staging of head and neck cancers are usually based on two classifications, namely cTNM and pTNM described in detail in the 8 th edition of the AJCC Cancer Staging Manual.
- A complete head and neck examination should be completed and documented (i.e. nose, postnasal space, oral cavity, oropharynx, larynx and hypopharynx, including palpation of neck, oral cavity and tongue base, using endoscopy as appropriate).
- When feasible, radiological investigations should be performed prior to biopsy to avoid the effect of upstaging from the edema caused by biopsy.
- When examination under general anesthesia including endoscopy and biopsy is indicated, that procedure should be performed by the surgeon who is responsible for any future procedures

# Imaging
CT Scan: 11. In all cases, CT of the neck with contrast is recommended for locoregional staging. If tumour extent is unclear on CT, and if clarification would alter management, then further evaluation with MRI is recommended.

# MRI Scan:
- MRI may be particularly helpful for assessing infiltration of surrounding soft tissues (e.g. extrinsic tongue muscles, parapharyngeal space, and masticator space), perineural spread, and intracranial/ intraorbital extension.

# FDG-PET Scan:
- If nodal status is unclear on CT (+/-MRI), and if clarification would alter management, then further evaluation with FDG-PET is recommended.
- In a patient with an unknown primary site of tumour after head and neck examination and CT (+/-MRI), FDG-PET should be performed prior to panendoscopy and biopsy so that sites of biopsy will not lead to a false-positive.
- Chest imaging is recommended for all newly diagnosed head and neck cancers to detect lung metastases and synchronous lung cancers. Both chest CT and PET-CT are superior to chest x-ray in detecting synchronous primary cancers and distant metastases 3 . In cases of N2-N3 disease, patients with a history of smoking and those otherwise at higher risk for second primary tumours and distant metastases (supraglottic and hypopharyngeal cancer), CT of the chest or PET-CT is strongly recommended 3,4 .
- In cases of stage III-IV disease, FDG-PET should be considered for screening for distant metastases and second primary cancers 3 . Interpretation should consider the relatively high false positive rate with PET-CT and the possible need for confirmatory diagnostic tests 5 .

# Diagnostic Biopsy
- It is essential that mucosal lesions of the oral cavity, oropharynx, nasopharynx, hypopharynx and larynx that are clinically suspicious for malignancy, primarily squamous cell carcinoma, be appropriately and adequately biopsied in an expedited manner. The approach and method of biopsy are dependent on the site and size of the lesion, the level of suspicion of malignancy, the resources available and experience of the clinician.
- Oral lesions over 2 cm in maximum dimension, highly suspicious oral lesions and ulcerated or clearly invasive oral lesions should be sampled with an incisional or punch biopsy. The biopsy site should not be in a necrotic or friable area. Generally, a biopsy near the edge of the tumour is ideal. A 4-mm dermatologic punch is a good choice, but scalpel blades or cupped biopsy forceps are acceptable. The biopsy needs to be adequately deep to allow determination of depth of invasion. Excisional biopsies of invasive cancers have a high incidence (62%) of leaving residual cancer requiring repeat excision 6 . This may complicate management but probably does not compromise overall disease control or survival if subsequently appropriately managed. It is suggested that excisional biopsies be reserved for small, superficial lesions that are thought to be benign 7 .
- Incisional biopsies of areas of oral leukoplakia risk false negative results of up to 24-73% in some series mostly due to sampling errors 8 . Small areas of leukoplakia without worrisome clinical features can be excised under local anesthesia. Excisional biopsies of larger or suspicious areas of leukoplakia should be performed under general anesthesia with adequate margins.
- All suspicious lesions of the pharynx and supraglottic larynx require biopsies with forceps. Accessible lesions of the soft palate and tonsils may be biopsied transorally without endoscopy. Suspicious lesions of the nasopharynx, oropharynx (base of tongue), hypopharynx and supraglottic larynx may be biopsied using topical anesthesia and endoscopic guidance (rigid or flexible). This requires the appropriate patient positioning, endoscopes, an experienced Otolaryngologist -Head and Neck Surgeon and often a skilled assistant 9 . When these conditions cannot be met then traditional biopsy under general anesthesia via rigid endoscopy is required.
- Suspected lesions of the tonsils are best sampled by way of an excision of the entire tonsil or tonsils under general anesthesia (diagnostic tonsillectomy). Blind biopsies of the tonsil have a very high false negative rate as cancers often arise deep in the tonsillar crypts and are missed unless they ulcerate through the surface 10 . These tonsillectomies are often done in conjunction with a panendoscopy in the setting of metastatic SCCA in a cervical node without an obvious mucosal lesion on office examination. Larger, ulcerated and clinically obvious cancers of the tonsil may be biopsied with forceps in the clinic.
- For biopsies of the glottis, in most cases, assessment and biopsy under general anesthesia using rigid laryngoscopes is required (suspension laryngoscopy). Larger lesions may be biopsied without magnification however early T1 cancers, leukoplakia, benign or indeterminate lesions of the glottis usually require adjuvant use of a microscope (suspension microlaryngoscopy). Larger or deeply invasive lesions are sampled with cupped laryngeal forceps. Superficial, benign and indeterminate lesions such as leukoplakia and erythroplasia may be suitable for excisional biopsy using either sharp "cold" instruments or a CO2 laser. Endoscopic biopsies of the glottis may sometimes be performed in clinic in selected patients by sub-specialist laryngologists in a highly specialized setting (regional voice clinic). Sensitivity and negative predictive values for in office biopsy techniques are reported from 60 -78% and 74 -87%, respectively.  . Lesions involving the anterior commissure of the glottis, bilateral vocal cords or vocal process of the vocal cord should not be excised without prior pathological confirmation and multidisciplinary consultation at a regional cancer centre with discussion of alternative non-surgical options. In performing excisional biopsies of suitable glottic lesions, care must be taken to not violate the vocal ligament or anterior commissure regardless of the instrument used.
- Panendoscopy as a diagnostic tool for the identification of synchronous tumours is inferior in comparison to CT or PET-CT in most cases  . Patients at low risk of a secondary lesion have a very low rate of synchronous tumours identified on routine pandendoscopy and esophagoscopy 14,15,17,18 Cancers of the hypopharynx may be an exception in that the incidence of esophageal second primaries is higher and esophagoscopy compares favourably to CT chest 4 .
- Panendoscopy is a useful tool in the workup of patients planned for surgery or potential transoral excision of a head and neck cancer to evaluate feasibility and anatomy.

# Occult Primary
- Fine Needle aspiration cytology of a neck mass or neck node should be performed for occult primaries. When the FNA is non-diagnostic an open biopsy may be required. Special stains including those for lymphoma, EBV and HPV testing should be ordered to help establish the primary tumour.
- PET-CT imaging is superior to panendoscopy in the identification of an occult primary and should be the initial investigation to establish the primary tumour. The PET-CT results may direct subsequent confirmatory biopsies. If PET-CT fails to detect a primary tumour, the patient should be sent for panendoscopy (EUA) for random directed biopsies of potential primary sites including tonsillectomy.
- The role of total mucosal resection for identification of unknown primaries is currently unclear.