Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over

This guideline covers assessing and managing cancers of the upper aerodigestive tract in people aged 16 and over. These are cancers of the airways of the head and neck, including the mouth, throat, larynx (voicebox) and sinuses. It aims to reduce variation in practice and improve survival.

# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.
Stages of upper aerodigestive tract cancer
The stages of upper aerodigestive tract cancer referred to in this guideline are based on the TNM classification 7th Edition:
T0: this means there is no primary tumour, but there may be abnormal cells that are precancerous.
T1 to T4: this refers to the increasing size and/or extent of the primary tumour, with 1 being smallest and 4 largest.
N0: no lymph nodes contain cancer cells.
N1 and upwards: increasing involvement of lymph nodes by cancer cells.

# Information and support

## Information needs
For people with cancer of the upper aerodigestive tract and their carers:
provide consistent information and support at diagnosis
review their needs throughout the care pathway including at the end of treatment
tailor information and support to the person's needs (including the benefits and side effects of treatment, psychosocial and longterm functional issues). 
Give people contact details for their allocated key worker, in line with NICE's cancer service guidance on improving outcomes in head and neck cancer and recommendations of the National Peer Review Programme. 
Give people details of peer support services that can help them throughout their care pathway. 
Offer information about human papillomavirus (HPV) to people with HPVrelated cancer of the upper aerodigestive tract. 

## Smoking cessation
Inform patients and carers at the point of diagnosis about how continuing to smoke adversely affects outcomes such as:
treatmentrelated side effects
risk of recurrence
risk of second primary cancers. 
Offer help to people to stop smoking, in line with NICE's guideline on tobacco: preventing uptake, promoting quitting and treating dependence. 

# Investigation

## Assessment of neck lumps
Consider adding ultrasoundguidance to fineneedle aspiration cytology or core biopsy for people with a neck lump that is suspected of being cancer of the upper aerodigestive tract. 
Consider having a cytopathologist or biomedical scientist assess the cytology sample adequacy when the procedure is carried out. 

## Identifying the occult primary
Consider a fluorodeoxyglucose positron emission tomography (FDG PET)CT scan as the first investigation to detect the primary site in people with metastatic nodal squamous cell carcinoma of unknown origin that is thought to arise from the upper aerodigestive tract. 
Consider using narrowband imaging endoscopy to identify a possible primary site when it has not been possible to do so using FDG PETCT. 
Offer a biopsy to confirm a possible primary site. 
Offer surgical diagnostic assessment if FDG PETCT does not identify a possible primary site. This may include:
guided biopsies
tonsillectomy
tongue base mucosectomy. 
Consider an MRI or CT scan before diagnostic surgery to help with radiotherapy treatment planning. 

## Clinical staging  who and how?
Offer systemic staging (see recommendations 1.2.91.2.11) to all people with cancer of the upper aerodigestive tract except those with T1N0 or T2N0 disease. 
Offer FDG PETCT to people with T4 cancer of the hypopharynx or nasopharynx. 
Offer FDG PETCT to people with N3 cancer of the upper aerodigestive tract. 
Offer conventional imaging (for example, chest CT) to people with cancer of the upper aerodigestive tract who require systemic staging (see recommendation 1.2.8) but FDG PETCT is not indicated for them. 

# Treatment of early stage disease

## Squamous cell carcinoma of the larynx
Offer transoral laser microsurgery to people with newlydiagnosed T1a squamous cell carcinoma of the glottic larynx. 
Offer a choice of transoral laser microsurgery or radiotherapy to people with newlydiagnosed T1bT2 squamous cell carcinoma of the glottic larynx. 
Offer a choice of transoral surgery or radiotherapy to people with newlydiagnosed T1T2 squamous cell carcinoma of the supraglottic larynx. 

## Management of the N0 neck in T12 squamous cell carcinoma of the oral cavity
Offer surgical management of the neck to all people with early oral cavity cancer (T1T2, N0). 
Offer sentinel lymph node biopsy instead of elective neck dissection to people with early oral cavity cancer (T1T2, N0), unless they need cervical access at the same time (for example, freeflap reconstruction). 

## Squamous cell carcinoma of the oropharynx (T12, N0)
Offer people the choice of transoral surgical resection or primary radiotherapy for T12 N0 tumours of the oropharynx. 
Consider postoperative radiotherapy, with or without concomitant chemotherapy, for T12 N0 tumours of the oropharynx if pathologically adverse risk factors have been identified. 

# Treatment of advanced disease

## Squamous cell carcinoma of the larynx
Offer people with T3 squamous cell carcinoma of the larynx a choice of:
radiotherapy with concomitant chemotherapy or
surgery with adjuvant radiotherapy, with or without concomitant chemotherapy. 
Discuss the following with people with T3 squamous cell carcinoma of the larynx and their carers, to inform their choice of treatment:
the potential advantages of laryngeal preservation
the risk of needing salvage laryngectomy (and its associated complications)
the benefits of primary surgery in people with existing compromised swallowing and airway function
likely voice and swallowing function after treatment (including the need for a longterm feeding tube). 
For people with T4a squamous cell carcinoma of the larynx consider surgery with adjuvant radiotherapy, with or without concomitant chemotherapy. 

## Squamous cell carcinoma of the hypopharynx
Offer larynxpreserving treatment to people with locallyadvanced squamous cell carcinoma of the hypopharynx if radiation and neoadjuvant and/or concomitant chemotherapy would be suitable for them and they do not have:
tumourrelated dysphagia needing a feeding tube
a compromised airway
recurrent aspiration pneumonias. 
Offer radiotherapy with neoadjuvant and/or concomitant chemotherapy if larynxpreserving treatment is suitable for the person. 
Offer primary surgery followed by adjuvant radiotherapy to people if chemotherapy is not a suitable treatment for them. 
Offer adjuvant radiotherapy to people having surgery as their primary treatment. Add concomitant chemotherapy if appropriate. 

## Palliation of breathing difficulties
Identify people at risk of airways obstruction for whom intervention is appropriate. Think about:
their performance status
treatment side effects and length of hospital stay
involving the palliative care team and other specialists when appropriate. 
Consider endoluminal debulking in preference to tracheostomy. 
Establish a management plan if surgical intervention is not appropriate, in conjunction with the person, carers and clinical staff. 
Assess and treat other causes of breathlessness in people with incurable upper aerodigestive tract cancer. 

## Genomic biomarker-based treatment
The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain. See the NICE topic page on genomic biomarker-based therapy.

# Response assessment after chemoradiotherapy
Offer FDG PET-CT to guide management for people treated with radical chemoradiotherapy who have:
an oropharyngeal primary cancer site and
-r more positive nodes in the neck, all of which are less than 6 cm across. The term 'radical chemoradiotherapy' refers to treatment aiming to cure cancer rather than to relieve symptoms (palliative treatment). It is used here to reflect the evidence that these recommendations are based on. 
Consider FDG PET-CT to guide management for people treated with radical chemoradiotherapy who have:
an oropharyngeal primary site with 1 positive node in the neck that is less than 6 cm across or
an oropharyngeal primary site with 1 or more positive nodes larger than 6 cm across in the neck or
a hypopharyngeal or laryngeal primary site with 1 or more positive nodes in the neck. 
For people having an FDG PET-CT scan after chemoradiotherapy, perform the scan 3 to 6 months after chemoradiotherapy has finished. 
Do not offer neck dissection to people with no abnormal FDG uptake or residual soft tissue mass on an FDG PET-CT scan. 
For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on response assessment after chemoradiotherapy .
Full details of the evidence and the committee's discussion are in evidence review A: evidence reviews for treatment of advanced disease
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# HPVrelated disease

## HPV testing
Test all squamous cell carcinomas of the oropharynx using p16 immunohistochemistry. Regard the p16 test result as positive only if there is strong nuclear and cytoplasmic staining in more than 70% of tumour cells. 
Consider highrisk HPV DNA or RNA insitu hybridisation in all p16positive cancers of the oropharynx to confirm HPV status. 

## Deintensification of treatment
Do not offer deintensification of curative treatment to people with HPVpositive cancer of the oropharynx, unless it is part of a clinical trial. 

# Less common upper aerodigestive tract cancers

## Carcinoma of the nasopharynx
Offer intensitymodulated radiation therapy with concomitant chemotherapy to people with locallyadvanced (stage II and above) nasopharyngeal cancer. 
Consider adjuvant or neoadjuvant chemotherapy for people with locallyadvanced (stage II and above) nasopharyngeal cancer. 

## Carcinoma of the paranasal sinuses
Offer surgery as the first treatment for carcinoma of the paranasal sinuses if complete resection is possible. 
Consider radiotherapy with or without concomitant chemotherapy before planned surgical resection of the paranasal sinuses if complete resection is not initially possible. 

## Unknown primary of presumed upper aerodigestive tract origin
Offer people with squamous cell carcinoma in the cervical lymph nodes with an unknown primary the choice of:
neck dissection and adjuvant radiation with or without chemotherapy or
primary radiation with or without chemotherapy, with surgery for persistent disease. 
Consider no further treatment as an option in people with pN1 disease without extracapsular spread after neck dissection. 
Consider including potential primary tumour sites when selecting the volume to be treated with radiotherapy. 

## Mucosal melanoma
Consider surgery and adjuvant radiotherapy for people with newlydiagnosed upper aerodigestive tract mucosal melanoma without systemic metastases. 

## Genomic biomarker-based treatment
The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain. See the NICE topic page on genomic biomarker-based therapy.

# Optimising rehabilitation and function

## Enteral nutrition support
Assess people's need for enteral nutrition at diagnosis, including prophylactic tube placement. The multidisciplinary team should take into account:
performance status and social factors
nutritional status (weight loss, high or low BMI, ability to meet estimated nutritional needs)
tumour stage
tumour site
preexisting dysphagia
impact of planned treatment (such as radiation treatment volume and dosefractionation, concomitant chemotherapy, and extent and site of surgery). 
Follow the recommendations in NICE's guideline on nutrition support for adults for people aged 18 years and over. 

## Speech and language therapy interventions
Consider swallowingexercise programmes for people having radiotherapy. 
Consider mouthopening exercises for people having radiotherapy who are at risk of reduced mouth opening. 
Consider voice therapy for people whose voice has changed because of their treatment. 

## Shoulder rehabilitation
Consider progressive resistance training for people with impaired shoulder function, as soon as possible after neck dissection. 

# Followup of people with cancer of the upper aerodigestive tract and management of osteoradionecrosis

## Followup
Ensure people with cancer of the upper aerodigestive tract and their carers have tailored information about the symptoms of recurrence and late effects of treatment at the end of curative therapy. 
Consider structured, riskadapted followup using locallyagreed protocols for people who have had curative treatment for cancer of the upper aerodigestive tract. Use the followup protocols to:
help improve quality of life, including discussing psychosocial issues
detect disease recurrence or second primary cancer, possibly including narrowband imaging to improve detection. 

## Management of osteoradionecrosis
Consider surgery to remove necrotic bone and to establish soft tissue coverage in people with osteoradionecrosis. 
Only consider hyperbaric oxygen therapy or medical management for treating osteoradionecrosis as part of a clinical trial. # Recommendations for research
The 2016 guideline committee made the following recommendations for research, marked . The guideline committee's full set of research recommendations is detailed in the full version of the guideline. As part of the 2018 update, the standing committee further research recommendations, marked . Full details of these can be found in evidence review A.

# Indeterminate FDG PET-CT after radical chemoradiotherapy: long-term outcomes
What are the long-term outcomes for people with an indeterminate fluorodeoxyglucose positron emission tomography (FDG PET)-CT scan result (a residual mass with no abnormal FDG uptake) after radical chemoradiotherapy?

## Why this is important
People with indeterminate FDG PET-CT results receive neck dissection surgery according to current practice in the UK. However, there is no standardised practice on long-term follow-up for people with negative disease and persistent nodes on FDG PET-CT scan. Research to investigate long-term outcomes could improve clinical outcomes and efficient use of resources. Randomised controlled trials or prospective cohort studies would be used to answer this research question. Outcomes of interest include recurrence rates, overall survival, quality of life, surgical complications, and adverse events. 

# Indeterminate FDG PET-CT after radical chemoradiotherapy: investigations
What are the most appropriate investigations for people with an indeterminate FDG PET-CT scan result (a residual mass with no abnormal FDG uptakes) after radical chemoradiotherapy?

## Why this is important
People with indeterminate FDG PET-CT results receive neck dissection surgery according to current practice in the UK. However, there is no standardised practice on long-term follow-up for people with negative disease and persistent nodes on FDG PET-CT scan. Research to investigate appropriate investigations could improve clinical outcomes and efficient use of resources. Randomised controlled trials or prospective cohort studies would be used to answer this research question. Investigations include interval FDG PET-CT, ultrasound with or without biopsy, multi-parametric MRI, and serial imaging. 

# Management of nodal metastasis in nasopharynx cancer after chemoradiotherapy
What is the optimal management strategy of nodal metastasis in nasopharynx cancer after chemoradiotherapy?

## Why this is important
There is evidence that FDG PET-CT is cost-saving, prevents unnecessary surgeries and reduces recurrence and overall mortality compared with neck dissection surgery in people who have received chemoradiotherapy. However, the evidence is only for people with oropharyngeal, laryngeal and hypopharyngeal cancer and there is no evidence on people with nasopharynx cancer. Natural history and response to treatment of cervical nodal metastases from nasopharynx primary sites are different, in terms of their impact on prognosis (TNM 7 cancer staging manual), and nasopharynx cancer is highly sensitive to radiotherapy and should not be treated by neck dissection (PET-NECK NIHR report). Research to investigate the optimal management of nodal metastasis in people with primary nasopharynx cancer after chemoradiotherapy could improve clinical outcomes and the use of resources. Outcomes of interest include recurrence rates, overall survival, quality of life, surgical complications, and adverse events. 

# Effectiveness of FDG PET-CT to guide follow-up
What is the effectiveness and cost-effectiveness of using FDG PET-CT to guide follow-up after treatment for people with head and neck cancer?

## Why this is important
There is evidence that FDG PET-CT is cost-saving, prevents unnecessary surgeries and has similar results for recurrence and overall mortality compared with neck dissection surgery in people with oropharyngeal, laryngeal and hypopharyngeal cancer who have received chemoradiotherapy. However, there is no evidence on FDG PET-CT for follow-up after other head and neck cancer treatments. Research to investigate the effectiveness of FDG PET-CT to guide follow-up could improve clinical outcomes and the use of resources. Outcomes of interest include recurrence rates, overall survival, and quality of life. 

# Systemic imaging  who and why?
What factors determine the risk of a person presenting with cancer of the upper aerodigestive tract having metastasis or a second primary cancer?

## Why this is important
Outcomes of interest include prevalence, predictive value and how the abnormalities identified influence patient management. The presence of metastasis or a synchronous second primary cancer at presentation is rare in patients with cancer of the upper aerodigestive tract. Subgroups of patients have been identified in whom the risk is clearly elevated. However, it is not clear at which level of risk detailed staging investigations are justified and the impact the results of these would have on decision making by the clinicians and the patient. Health economic modelling is needed to inform this process. 

# HPV testing
What is the comparative effectiveness of singlestep laboratory diagnostic tests to identify human papillomavirus (HPV) against current diagnostic test algorithms and reference standards in people with cancer of the oropharynx?

## Why this is important
Outcomes of interest are sensitivity, specificity and resource use. HPV testing is currently recommended in cancer of the oropharynx because it has significant prognostic implication. Current methods use a 2step procedure that is not widely available in all treatment centres. A singlestep test is likely to be more widely adopted and could have significant budgetary implications for the NHS. The study should also consider the prognostic value and the economic benefits of novel tests. 

# Unknown primary of presumed upper aerodigestive tract origin
In people with cancer of the upper aerodigestive tract of unknown primary, can radiotherapy target volumes be selected based on clinical and pathological factors?

## Why this is important
Outcomes of interest include local control, progressionfree survival, overall survival, and treatmentrelated morbidity and mortality. In a very small percentage of patients with squamous carcinoma involving a cervical lymph node the primary site remains occult despite intensive investigations. The optimum treatment for these patients is uncertain. Some clinical teams will treat the neck disease alone and others will treat some or all potential primary sites with the radiotherapy with or without chemotherapy. The latter strategy is associated with a high level of side effects that may have lifelong consequences, for example xerostomia. A better understanding of the clinicpathological factors associated with treatment outcomes would improve treatment selection with the potential to reduce these side effects. 

# Enteral nutrition support
What specific clinical and nonclinical factors allow risk stratification when selecting which people with cancer of the upper aerodigestive tract would benefit from short or longterm enteral nutrition?

## Why this is important
Outcomes of interest include resource use, morbidity of tube placement, duration of enteral feeding and nutritional status. There are no nationally agreed selection criteria for the type of feeding tube placed at diagnosis for people who need enteral nutrition support during curative treatment. Variation across the UK exists as a result of clinicianled practices and local policy. The systematic review by NICE in 2015 found some evidence but no specific list was identified because of limitations with study design, and inability to stratify clinical and nonclinical factors meaningfully. These factors included restricted populations for tumour staging, patient demographics, treatment plan and intent, definitions of malnutrition, timing and method of tube placement, and duration of enteral nutrition. 

# Followup
What is the optimal method, frequency and duration of followup for people who are diseasefree after treatment for cancer of the upper aerodigestive tract?

## Why this is important
Outcomes of interest include quality of life, local control and overall survival. The optimal methods, frequency, and duration of followup in people who are clinically diseasefree and who have undergone treatment for squamous cell cancer of the upper aerodigestive tract with curative intent are not known. Considerable resources are expended throughout the country on the followup of people who have completed potentially curative treatment. Local followup protocols are based more on historical practice than evidence and are often disease rather than patientcentred. Research to investigate how and when followup should optimally be carried out could improve clinical outcomes and the use of resources. # Rationale and impact

# Response assessment after chemoradiotherapy
Recommendations 1.5.1 to 1.5.4

## Why the committee made the recommendations
Overall, the evidence showed that recurrence rates and overall mortality for fluorodeoxyglucose positron emission tomography (FDG PET)-CT-guided management after radical chemoradiotherapy were similar to those for neck dissection. In addition, the evidence showed that FDG PET-CT was cost-saving compared with neck dissection, and would prevent unnecessary surgeries, surgical complications, and adverse events.
The committee agreed to make recommendations only for people with oropharyngeal, laryngeal and hypopharyngeal primary sites, because these were the main focus of the evidence. Most of the people in the study had an oropharyngeal primary site and more than 1 positive node under 6 cm across in the neck, and the evidence was strongest for this population. Therefore, the committee agreed that they should be offered an FDG PET-CT scan.
The evidence was weaker for people with:
an oropharyngeal primary site and 'N2a' stage disease (only 1 positive node of more than 3 cm but no more than 6 cm across)
an oropharyngeal primary site and higher 'N' stage disease (1 or more positive node larger than 6 cm across in the neck)
laryngeal or hypopharyngeal primary sites.
To reflect this, FDG PET-CT scanning could be considered for these groups.
The evidence did not include people with an oropharyngeal primary site and 'N1' stage disease (only 1 positive node of less than 3 cm across). However, the committee agreed that it is particularly important that FDG PET-CT scans are considered for this population to avoid unnecessary surgery. These people are likely to be at a lower risk of recurrence and so the benefits of neck dissection are lower.
The committee noted that new classifications for head and neck cancer (TNM classification of malignant tumours, 8th edition) have been introduced, which are different from those used in the evidence. They decided to describe the stage of cancer for these recommendations in terms of the number and size of positive nodes to avoid confusion.
The timing of FDG PET-CT scans (3 to 6 months after completion of radical chemoradiotherapy) is in line with current Royal College of Radiologists guidelines on the use of PET-CT. Scans earlier than 3 months are more likely to give a false-positive result, due to the residual effects of treatment.
The committee decided to be specific that neck dissection should not be offered to people with no abnormal FDG uptake or residual soft tissue mass, to give clear advice about how to interpret a 'negative' FDG PET-CT result.
The committee noted several areas in which future research would be helpful, such as management for people with indeterminate test results (see research recommendations 1 and 2), the role of FDG PET-CT for people with nasopharyngeal cancer (see research recommendation 3) and the effectiveness of FDG PET-CT to guide follow-up (see research recommendation 4).

## How the recommendations might affect practice
There may an increase in the number of FDG PET-CT scans performed and a reduction in surgical procedures. However, the evidence showed that the amount of money saved from unnecessary surgery is likely to be considerably higher than the cost of the additional scans.
Full details of the evidence and the committee's discussion are in evidence review A: evidence reviews for treatment of advanced disease.# Context
Upper aerodigestive tract cancers are found at various sites in the airways of the head and neck: the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx and nasal sinuses. The majority are squamous cell cancers. The major risk factors for upper aerodigestive tract squamous cell cancer in the UK are tobacco smoking and alcohol consumption.
There is currently variation or uncertainty in the investigations used to assess neck lumps; who needs systemic staging, the most effective treatment for early stage and advanced disease, how to best identify HPVpositive disease, how to optimise function and rehabilitation, the most effective followup and the management of osteoradionecrosis of the jaw. This guideline aims to make recommendations that address these areas of variation or uncertainty.
This guideline will cover adults and young people (16 years and older):
referred from primary care with suspected cancer of the upper aerodigestive tract
with newlydiagnosed or recurrent cancer of the upper aerodigestive tract.
It will not cover:
adults and young people with cancers of the thyroid, orbit, middle ear, cutaneous lip, skull base or salivary gland
adults and young people with sarcoma or lymphoma
children and young people under 16 years.
Since publication, new evidence was identified on the use of fluorodeoxyglucose positron emission tomography (FDG PET)-CT scanning to inform decisions about surgery for nodal metastases after radical chemoradiotherapy. This less invasive approach to management has the potential to reduce unnecessary surgery for people with locally advanced head and neck cancer. In 2018 we reviewed this evidence and added new recommendations.