Head and Neck Cancer Diagnosis, Staging and Treatment

Head and neck cancer diagnosis rests on tissue: histology confirms the cancer, imaging stages it and a multidisciplinary team plans treatment. The pathway runs from examination and endoscopy to biopsy or fine needle aspiration cytology (FNAC), then imaging, TNM staging and a tumour board plan. Biomarkers such as p16, EBV and PD-L1 now shape that plan, and treatment combines surgery, radiotherapy, chemotherapy and immunotherapy according to stage and site.

Dr. Priyanka Raina, Senior Consultant (Head & Neck Surgery) - Surgical Oncology, Artemis Hospitals, Gurugram, India, walked through each step as her team practises it, from the tests ordered on every biopsy to the reasons two apparently identical tongue cancers can behave differently. This article covers what happens once a patient reaches a specialist centre. How to recognise and refer a suspected case is covered in the article on red flags and urgent referral, and the overview of the specialty is in the complete guide to head and neck oncology.

How head and neck cancer is diagnosed: the pathway

Dr. Raina described a five-step sequence:

1. Examination, including endoscopy or a structured oral examination.
2. Tissue diagnosis, by biopsy or FNAC.
3. Imaging to define the extent of disease.
4. Staging.
5. A multidisciplinary tumour board that agrees the treatment plan.

The order can change with the subsite and with the patient's clinical stability; a patient in airway distress is stabilised before anything else.

Better visualisation before biopsy

Nothing replaces histology: until tissue confirms the diagnosis, better visualisation alone settles nothing. It is still valuable for deciding what the clinician is looking at and where to sample. Dr. Raina's clinic uses:

• High-definition oral examination with flexible endoscopy.
• Zero-degree endoscope cameras for patients with grade 3 or grade 4 trismus (severely restricted mouth opening), where direct inspection of the oral cavity is difficult.
• Narrow band imaging, a filtered-light technique that highlights abnormal surface blood vessels, to pick the best biopsy site in diffuse leukoplakia (a white patch on the lining of the mouth) and other potentially malignant disorders.
• Autofluorescence and related techniques.

Biopsy and FNAC: confirming the diagnosis

Biopsy is the best method of diagnosis. In some sites, such as the thyroid, FNAC, in which cells are drawn through a fine needle, is enough to establish the diagnosis.

CT, MRI or PET-CT: choosing imaging for head and neck cancer

Dr. Raina's rule is to choose imaging for the clinical question, not by habit:

• Contrast-enhanced CT shows tumour extent, bone involvement and the cervical lymph node beds, and assesses the chest.
• MRI is best for soft tissue, the skull base and perineural invasion (spread along nerves). When perineural invasion is suspected, MRI is required.
• PET-CT is used for staging and for detecting recurrence.
• Endoscopy is central in the search for a primary tumour of unknown origin.

Investigations should match the site, the extent of disease, local availability and the specialist pathway, and should never delay a referral.

Nuclear imaging and precision staging

FDG PET-CT has changed practice. Where clinicians once performed repeated endoscopies and multiple punch biopsies to find and stage a tumour, PET-CT now guides diagnosis and staging far more directly, although histology still confirms the diagnosis. Dr. Raina's centre also uses targeted tracers for specific tumours:

• 18F-fluorocholine PET to localise abnormal parathyroid glands.
• Technetium-99m sestamibi scanning, also for the parathyroids.
• 68Ga-DOTANOC PET for medullary thyroid carcinoma and paragangliomas.

Biomarker testing: p16, EBV and PD-L1

Alongside routine histopathology, Dr. Raina's team runs a standing biomarker protocol:

• p16 immunohistochemistry on every oropharyngeal sample, as a marker of HPV-associated oropharyngeal cancer. HPV status matters because HPV-positive tumours generally carry a better prognosis and are the focus of treatment de-escalation strategies. De-escalation is still being evaluated in clinical trials and is not yet standard care outside them.
• EBV testing for nasopharyngeal cancer.
• PD-L1 expression with a combined positive score (CPS) for squamous cell carcinoma of the oral cavity, to guide the selection of immunotherapy.
• Molecular profiling and gene sequencing for some thyroid and salivary gland tumours, to direct targeted therapy.

A more detailed pathology report

Dr. Raina gave a pointed example of why biomarkers and detailed pathology matter. Two patients with tongue cancer, of the same age and with the same depth of invasion, may not respond the same way: one recurs and the other does not. To personalise treatment, her team's histopathology reports go beyond the traditional parameters to include features such as tumour budding and tumour-infiltrating lymphocytes. She sees these details as also informing decisions on immunotherapy with drugs such as pembrolizumab and nivolumab; in current guidelines, PD-L1 CPS, not these histological features, is the biomarker used to select patients for pembrolizumab.

Head and neck cancer staging: TNM and why it changes management

Staging follows the TNM system:

• T (tumour): the size and extent of the primary tumour and its anatomical subsite.
• N (nodes): the nodal burden, whether nodes are on one or both sides, and extranodal extension (cancer breaking through the node capsule).
• M (metastasis): whether the cancer has spread to distant organs.

Stage alone does not decide treatment. In Dr. Raina's formulation, stage plus pathology plus the patient's fitness, function and preferences determine the plan.

Head and neck cancer treatment by stage

Treatment is always stage-specific and site-specific:

• Early-stage oral cavity cancer is usually resectable; adjuvant treatment may or may not be needed.
• Early-stage laryngeal cancer can often be treated with a voice-preservation approach.
• Locally advanced oral cavity disease is treated with surgery followed by risk-adapted adjuvant treatment; at sites such as the larynx and oropharynx, chemoradiotherapy is often an alternative to primary surgery.
• Recurrent and metastatic disease receives individualised systemic therapy, radiotherapy, surgery in selected cases, clinical trial options and symptom-directed care.

The principles of head and neck cancer surgery

Surgery has three components in Dr. Raina's practice.

Resection of the primary tumour. Oncologic clearance comes first. Function and appearance are planned at the outset, not as an afterthought.

Management of the neck. Addressing the neck is mandatory in her protocol. Guidelines recommend elective treatment of the neck wherever the risk of hidden nodal spread is significant, as in most oral cavity cancers, but not, for example, in early glottic cancer (cancer of the vocal cords). Dr. Raina cited the trial by D'Cruz and colleagues, published in 2015, which compared elective neck dissection with a wait-and-watch approach followed by therapeutic dissection in early oral cancer and found that elective dissection improved overall survival.

Reconstruction. She regards reconstruction as the most important part: the surgeon's skill lies not only in resecting the tumour well but in rebuilding so the patient can swallow and speak and looks as normal as possible. Advanced reconstruction techniques are, in her view, the patient's right.

Rehabilitation before and after the operation

For tongue cancer, her protocol sends every patient to a speech and swallowing therapist both before and after surgery. Training and strengthening the tongue muscles before the operation improves function afterwards.

Minimally invasive options for early disease

Early-stage cancers can often be treated with minimal-access surgery, such as transoral endoscopic laser surgery or transoral robotic surgery. The principle does not change with the technique: oncologic clearance first, then function and appearance.

Frozen section as standard

Dr. Raina's team sends every resected tumour for frozen section, an intraoperative pathology check, to confirm clear margins. This is especially important in difficult tumours where repeated biopsies have come back negative and no diagnosis exists before surgery.

Radiotherapy, chemotherapy and immunotherapy for head and neck cancer

Radiotherapy and chemotherapy are major partners to surgery. Modern radiotherapy techniques, including image-guided radiotherapy (IGRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), aim to deliver the best tumour control with the fewest side effects. Cost guidance for these treatments is on the radiation therapy cost page and the chemotherapy cost page.

Over the last decade, Dr. Raina noted, new chemotherapy regimens and the arrival of immunotherapy and targeted therapy have markedly improved both quality of life and outcomes. PD-L1 testing with CPS is routine in her practice, and she regards immunotherapy, given in the neoadjuvant setting (before surgery) or the adjuvant setting (after it), as genuinely helpful in advanced disease. The phase 3 KEYNOTE-689 trial found that adding pembrolizumab before and after surgery improved event-free survival in resectable, locally advanced head and neck squamous cell carcinoma.

A case of neoadjuvant immunotherapy

Dr. Raina presented a man in his fifties with a large tongue cancer extending to the mandible. PD-L1 and CPS were measured on the biopsy sample. With the aim of preserving the organ, he received three cycles of neoadjuvant chemotherapy combined with immunotherapy. The tumour responded strikingly. At surgery, pathology showed no residual primary tumour (T0), although nodal disease (N2b) remained. She described such responses as the "magic" immunotherapy sometimes delivers. Neoadjuvant chemotherapy combined with immunotherapy is not yet a guideline standard; the approved perioperative regimen, from KEYNOTE-689, gives pembrolizumab alone before surgery. Cost guidance is on the immunotherapy cost page.

Why personalised treatment matters

The thread running through Dr. Raina's approach is personalisation: identical-looking tumours behave differently, and the extra information from biomarkers, detailed pathology and functional assessment is what allows the team to choose between upfront surgery, neoadjuvant therapy and radiotherapy. Survival and quality of life are weighed alongside tumour control at every step. The surgical techniques and reconstruction that make function-preserving treatment possible are described in the article on surgical advances and voice rehabilitation.

Questions from doctors on imaging without PET-CT and on screening are answered on the Live Discussion page, and Dr. Raina's training is listed on her profile.