Overview of approach to long-term survivors of

head and neck cancer

Authors: Robert I Haddad, MD, Sewanti Limaye, MD
Section Editor: Larissa Nekhlyudov, MD, MPH
Deputy Editor: Melinda Yushak, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2024. | This topic last updated: Nov 29, 2022.

INTRODUCTION

The term "cancer survivor" has been used variably in the literature; in general, a
cancer survivor refers to any person who has been diagnosed with cancer until the
end of life. There are more than half a million survivors who have been rendered
cured of head and neck cancer in the United States [1]. The steady increase in the rate
of head and neck cancer survivors is likely due to advances in treatment, decrease in
smoking rates, and the improved prognosis associated with oropharyngeal
carcinomas associated with human papillomavirus (HPV) infection [2]. (See
"Epidemiology, staging, and clinical presentation of human papillomavirus associated
head and neck cancer".)

This topic will review the long-term issues of survivors of head and neck squamous
cell carcinoma (HNSCC), specifically discussing the group of survivors who are without
evidence of disease for at least five years [3,4]. Other topics that discuss
complications and quality of life in patients following a diagnosis of head and neck
cancer are covered separately.
● (See "Health-related quality of life in head and neck cancer".)
● (See "Management and prevention of complications during initial treatment of
head and neck cancer".)
● (See "Management of late complications of head and neck cancer and its
treatment".)
OVERVIEW OF HEAD AND NECK CANCER

Primary tumor sites — Survivors of head and neck cancer may have been treated for
disease arising from one of five anatomic regions of the head and neck. Further
details on these specific primary tumor sites are discussed separately (see "Overview
of the diagnosis and staging of head and neck cancer", section on 'Anatomic
subsites'):
● The oral cavity (lips, buccal mucosa, anterior tongue, floor of the mouth, hard
palate, and upper and lower gingiva)
● The pharynx (nasopharynx, oropharynx, and hypopharynx)
● The larynx (supraglottic, glottic, and subglottic regions)
● The nasal cavity and paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal)
● The salivary glands (parotid, submandibular, sublingual, and the minor glands)

Staging — The Tumor, Node, Metastasis (TNM) staging system of the American Joint
Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC) is
used to classify cancers of the head and neck. TNM staging, which is based on
primary tumor site, also impacts prognosis and follow-up in the long-term survivor of
head and neck cancer. Further details on the staging of head and neck cancer are
discussed separately. (See "Overview of treatment for head and neck cancer", section
on 'TNM staging system'.)

Treatment — The management of head and neck squamous cell carcinoma (HNSCC)
is based on whether the disease is early or advanced stage and the primary site of the
tumor. Treatment modalities include surgery, radiation therapy (RT), and systemic
therapies. Such treatment may impact prognosis, follow-up, and long-term
complications in the survivor of head and neck cancer. Specific discussions for the
management of early versus advanced disease by primary site are discussed
separately. (See "Overview of treatment for head and neck cancer".)

Prognosis — The prognosis of HNSCC depends on stage at presentation and the site
of involvement.
Five-year overall survival in patients with stage I or stage II disease is typically 70 to 90
percent. By contrast, the prognosis for patients who present with more advanced
(stage III or IV) disease is poorer. As an example, patients with locoregionally
advanced laryngeal carcinoma have an approximately 40 percent overall survival rate
at five years. However, in patients with tobacco- and alcohol-related cancers, a 20
percent rate of second malignancy might be expected over five years.

For patients with human papillomavirus (HPV) associated locoregionally advanced

disease, long-term survival rates are higher than those without HPV associated
disease. (See "Epidemiology, staging, and clinical presentation of human
papillomavirus associated head and neck cancer", section on 'Prognosis'.)

GUIDELINES FOR FOLLOW-UP, SURVEILLANCE, AND SECONDARY

PREVENTION IN THE LONG-TERM SURVIVOR

In general, the intensity of follow-up is greatest in the first two to four years following
diagnosis, since approximately 80 to 90 percent of all recurrences occur within this
timeframe. However, patients should continue to be followed beyond five years
because of the risk of late complications, as well as the risk of late recurrence or
second malignancies. This may be especially important for patients without human
papillomavirus (HPV) associated oropharyngeal cancers. (See "Posttreatment
surveillance of squamous cell carcinoma of the head and neck".)

There are no data to guide the continued follow-up of the long-term head and neck
squamous cell carcinoma (HNSCC) survivor. In general, these patients are seen for
visits with an oncologist on an annual basis, highlighting the importance of
coordinated care.

Components of follow-up — An overview of cancer survivorship for both primary

care and oncology clinicians is covered separately. While not specific to HNSCC
survivors, the issues discussed are relevant to this population as well. (See "Overview
of cancer survivorship care for primary care and oncology providers".)

Head and neck cancer survivors should have a detailed cancer-specific follow-up every
one to three months for the first year, every two to six months in the second year,
every four to eight months during years 3 to 5, and annually beginning five years
after the primary treatment. This should include [3-6]:
● History, including screening for any symptoms that might suggest a local
recurrence (eg, new swelling, cough, dysphagia) or metastatic disease (eg,
shortness of breath). Other than post-treatment baseline imaging of the primary
and the neck if treated, there is no role of routine serial imaging in long-term
survivors of head and neck cancer unless otherwise indicated by new signs or
symptoms. However, patients with over 20 or more pack-years of smoking history
would be candidates for annual low-dose helical computed tomography (CT) scan
of the lung. Surveillance for recurrences is based on detailed clinical examination
and fiberoptic visualization by the multidisciplinary treatment team. Utilization of
imaging for follow-up should be done on a case-by-case basis for high-risk
features or clinical indications. (See "Screening for lung cancer".)
● The history should also include any interval changes in the social environment
(including partner status, life events, living arrangements, and occupational
issues), lifestyle factors (eg, smoking and alcohol consumption), and an
evaluation of sexual health and body image issues.
● Physical exam, including thorough inspection of the head and neck region, and
periodic fiberoptic visualization and dental evaluation. (See "Posttreatment
surveillance of squamous cell carcinoma of the head and neck".)
● Patients with history of radiation therapy to the neck should have serum thyroid-
stimulating hormone (TSH) levels every 6 to 12 months due to the risk of
hypothyroidism.
● Encouragement of a healthy lifestyle, including assessment of diet and
encouragement to remain (or become more) physically active. (See "The roles of
diet, physical activity, and body weight in cancer survivors".)
● Encouragement and education about cessation of smoking and the limiting of
alcohol consumption for any survivor who continues to partake in either or both.
(See 'Smoking and alcohol cessation' below and "Management of late
complications of head and neck cancer and its treatment", section on 'Smoking
 cessation' and "Overview of cancer survivorship care for primary care and
oncology providers", section on 'Limitation in alcohol consumption'.)
● A speech, hearing, and swallowing evaluation and rehabilitation where clinically
indicated should be performed.
● Age-appropriate screening for other malignancies.

Smoking and alcohol cessation — It is critical to encourage and educate head and
neck cancer survivors about smoking cessation and limiting alcohol consumption
[6,7]. Higher rates of secondary cancers are seen in survivors who continue to smoke
or consume alcohol [8,9]. In addition, due to the synergistic effects of alcohol and
smoking, survivors exposed to both together are at higher risk for recurrence and
death. (See "Overview of cancer survivorship care for primary care and oncology
providers", section on 'Risk of subsequent primary cancer'.)

Even light alcohol consumption of less than one drink per day has been shown to be
associated with oral cavity, oropharyngeal, and esophageal cancers in a meta-analysis
[10]. A study of 165 survivors showed a persistent smoking and alcohol dependence
in males, with young age and single status making a special case for referral to formal
cessation programs for such patients [11]. Aggressive counseling for lifestyle
modification including smoking and alcohol cessation should be provided at each
follow-up visit. A combination of behavioral support and pharmacologic therapy may
be needed. (See "Overview of smoking cessation management in adults" and "Alcohol
use disorder: Psychosocial management".)

Diet and exercise — Lifestyle changes including diet and exercise have a significant
impact on quality of life and secondary prevention in survivors. Pretreatment dietary
counseling may help in improving long-term outcomes for survivors and could involve
simple phone-based counseling for patients starting therapy [12]. In a meta-analysis
of cancer survivors, the highest adherence score to a Mediterranean diet was
significantly associated with a lower risk of all-cause cancer mortality (relative risk [RR]
0.87, 95% CI 0.81-0.93), also seen in head and neck cancer (RR 0.40, 95% CI 0.24-0.66)
[13].

Exercise and physical activity in head and neck cancer survivors has been associated
with improved quality of life and should be encouraged and incorporated in their
counseling process [14,15]. (See "The roles of diet, physical activity, and body weight
in cancer survivors".)

LATE AND LONG-TERM COMPLICATIONS

Much of our understanding of the issues in head and neck squamous cell carcinoma
(HNSCC) survivors comes from evaluations of patients followed for two to three years
after treatment, although there are several landmark papers describing issues of
long-term survivors [16-21]. As a result, there are little data to inform the issues
experienced in long-term HNSCC survivors who are without evidence of disease for
five years or more. However, they are at an increased mortality due to cancer and
other causes, which persists for up to 10 years after diagnosis. As an example, one
study evaluated almost 36,000 HNSCC survivors followed for a median of 7.7 years
after initial diagnosis (range, 3 to 17.9 years) [22]. The rates of death at 5 and 10 years
were 15.4 and 41 percent, respectively. Causes of death during follow-up consisted of:
● HNSCC (29 percent)
● Second primary malignancy (23 percent) with the most common malignancies
being primaries of the lung (53 percent), esophagus (10 percent), and colorectal
origin (5 percent)
● Cardiovascular disease (21 percent)
● Lung disease such as chronic obstructive pulmonary disease, pneumonia, and
influenza (23 percent)

These data highlight the importance of follow-up, which should be coordinated

between oncology and primary care. (See 'Coordination of care and specialist referral'
below.)

Head and neck toxicity

Dental complications and oral health — Oro-dental care and follow-up are very
important, especially after radiation therapy (RT) to the head and neck area. Poor oral
health has been linked with inferior survival and worse outcomes [23,24]. Worsening
of dental health after treatment is common and could lead to significant compromise
in quality of life of long-term head and neck cancer survivors. Deterioration of dental
and oral health is thought to be secondary to xerostomia, change in salivary pH to
acidic, demineralization, and decreased vascularity associated with radiation [16,25].
Gradual dental decline, xerostomia and difficulties with ill-fitting dentures, coupled
with the financial limitations including the lack of proper dental insurance coverage,
can add to the burden of long-term survivors. In addition, inadequate dental
rehabilitation results in a compromised ability to eat and has been directly linked to
poor quality of life due to compromised eating and chronic pain [16].

Although data on the late effects of mucositis are limited, the patient’s dental status
at one year post-treatment appears to be a strong predictor of quality of life of
survivors five years from completion of therapy [17]. The incidence of dental caries
increases 50-fold after RT and is seen at a rate of 2.5 per month [25,26]. They are
often highly destructive and lead to extractions and osteoradionecrosis in up to 15
percent of irradiated head and neck cancer patients [27,28]. Dental status was found
to have a direct impact on eating in public, chewing, swallowing, and normalcy of diet
[16].

Patients undergoing RT for head and neck cancers may develop mucosal atrophy and
telangiectasias, and may experience chronic mucosal pain and sensitivity [29].
Patients often describe the mucosal pain as a burning or a scalded sensation that
may represent neuropathy. Hot and/or spicy and acidic foods and dry air reportedly
exacerbate symptoms. Mucosal sensitivity may permanently alter food choices in this
population.

Management emphasizes attention to the risk factors of hyposalivation, mucosal

infection, and the neuropathic components of pain associated with mucositis [29].
Timely dental rehabilitation including dental restoration and dental prosthesis
development and fitting may help improve quality of life of survivors. Our approach is
consistent with the guidelines from the Department of Veterans Affairs and the
National Comprehensive Cancer Network (NCCN) [3,30]. Further discussion on the
oral complications and treatment guidelines for cancer survivors is covered
separately. (See "Oral health in cancer survivors", section on 'Approach to the cancer
patient'.)
 Xerostomia — Xerostomia or dry mouth is common in most head and neck
cancer survivors who have undergone radiation as a part of their treatment. It
remains one of the main late complications of RT and a leading cause of compromise
of quality of life of head and neck cancer survivors. There can be gradual recovery of
some salivary secretion over time, with maximum recovery one to two years post-
therapy [31-37], but this depends on the total radiation dose to the gland tissue.
Xerostomia is a long-lasting and frequently permanent problem that adversely
impacts quality of life, even years after diagnosis.

In long-term survivors (more than five years following treatment), symptoms of

xerostomia can include dry mouth, sticky saliva, persistent need to drink water or
fluids while eating, swallowing and speaking, difficulty eating and speaking, early
dental decline, and poor oral health [18,19]. In one study, xerostomia was present in
64 percent of long-term survivors at a mean follow-up of 9.6 years following RT [20].
There is decreased rate of xerostomia with intensity-modulated radiation therapy
(IMRT). In a study of long-term quality of life of head and neck survivors at five years
after IMRT, nearly 84 percent of survivors reported saliva "of normal consistency" or
"less saliva than normal but enough," and only 16 percent reported "too little saliva"
[38]. (See "Overview of the treatment of locoregionally advanced head and neck
cancer: The oropharynx", section on 'Radiation schedule and technique'.)

The management of xerostomia is discussed separately. (See "Management of late

complications of head and neck cancer and its treatment", section on 'Salivary gland
damage and xerostomia'.)

Osteoradionecrosis — Osteoradionecrosis can be seen in patients needing

dental restorations or extractions in previously radiated areas [39,40]. The incidence
of osteoradionecrosis with conventional RT or IMRT is in the range of 5 to 7 percent.
(See "Management of late complications of head and neck cancer and its treatment",
section on 'Osteoradionecrosis and soft tissue necrosis' and "Oral health in cancer
survivors", section on 'Osteonecrosis'.)

Trismus — Trismus or lockjaw could occur in up to 35 percent of head and neck

cancer patients following RT and in patients treated with surgery [41,42]. However,
these estimates appear to be lower for patients treated with IMRT (5 to 15 percent)
[41,43]. More commonly seen after oral cavity, oropharyngeal, and nasopharyngeal
cancer therapy, trismus is caused by inflammation and fibrosis of the pterygoid and
masseter muscles. It has an important repercussion on quality of life and could lead
to poor dental hygiene, worsening xerostomia, and dental complications [41].

Active and passive exercise should be initiated as soon as post-treatment fibrosis

becomes evident because if left untreated, it may impact the range of jaw movement.
Unfortunately, once there is restriction clinically evident it is difficult to reverse.
Pentoxifylline and botulinum toxin have been used to treat established trismus in
long-term survivors with some evidence of a symptomatic benefit, although no
objective improvement of trismus was seen [44,45]. (See "Oral health in cancer
survivors", section on 'Trismus' and "Management of late complications of head and
neck cancer and its treatment", section on 'Trismus' and "Physical rehabilitation for
cancer survivors", section on 'Trismus'.)

Dysphagia — Patients treated for HNSCC can experience dysphagia during

treatment and as both an acute and long-term complication. Speech and swallowing
impairment are seen in over 50 percent of head and neck cancer patients even before
the start of treatment [46]. In addition, impaired speech and swallow function are
common after oral or oropharyngeal surgery and in over 50 percent of patients
undergoing partial laryngectomy [47,48]. Subsequent malnutrition and unintended
weight loss can also exacerbate dysphagia due to a reduction in the will to eat and a
more global psychological toll on the patient.

Causes — A number of factors may result in or worsen dysphagia in long-term

survivors of head and neck cancer, including:
● Loss of normal anatomic structures and/or altered relationships between normal
structures (eg, loss of the hard palate or part of the larynx)
● Radiation-induced xerostomia and fibrosis
● Problems with dentition
● Trismus

Dysphagia may also result as a consequence of esophageal stenosis, which can occur
as a late complication of progressive RT-related fibrosis. The rate of long-term grade 3
esophageal strictures appears to be higher for patients treated with IMRT and is
thought to be due to a greater dose of radiation to pharyngeal constrictor muscles
[49,50]. As an example, the rates of a pharyngoesophageal stricture with IMRT and
conventional RT were 16.7 and 5.7 percent, respectively [50]. However, in another
study of patients with nasopharyngeal carcinoma, late toxicity was significantly less
severe with IMRT-based therapy rather than non-IMRT-based therapy, including
neuropathy, hearing loss, dysphagia, xerostomia, and neck fibrosis [51]. In
preliminary results from one phase III trial (DARS), dysphagia-optimized IMRT
improved patient-reported swallowing functions [52].

Clinical presentation — Patients who develop an esophageal stricture may

present with subtle or significant complaints, including dysphagia (eg, feeling
"something getting stuck in the throat/chest") or changing patterns of cough when
swallowing food, indicating possible episodes of aspiration. New symptoms or other
more subtle changes in a patient’s normal swallowing pattern should warrant a work-
up to rule out esophageal stenosis, especially if these symptoms are persistent. (See
"Approach to the evaluation of dysphagia in adults", section on 'Approach to
diagnostic testing'.)

Treatment approach — Even for patients who present with longstanding

dysphagia, we believe there is a role for cancer rehabilitation, including speech and
language therapists. Therapy consisting of swallowing exercises and maneuvers,
neuromuscular stimulation, and education regarding the importance of lifestyle
modification (eg, changing the food consistency to prevent aspiration) can help
prevent worsening (or more significant) morbidity. Speech and swallow rehabilitation
is an inherent part of the multidisciplinary team involved in treatment. The
rehabilitation services are freely available in the community as well. Dysphagia as a
late complication of HNSCC treatment and the role of rehabilitation is covered
separately. (See "Management of late complications of head and neck cancer and its
treatment", section on 'Dysphagia' and "Speech and swallowing rehabilitation of the
patient with head and neck cancer".)

Feeding tube utilization — Despite preventive measures employed prior to

and/or during treatment, 10 to 25 percent of HNSCC survivors become feeding tube-
dependent for life [19,53]. This is seen in survivors with compromised oral cavity
function due to treatment or those who have had multiple episodes of aspiration. The
psychosocial burden of clinically significant dysphagia should be recognized and
patients referred for counseling and support in order to prevent depression and
distress in survivors (and in their caregivers).

Neuromuscular toxicity — Several neuromuscular complications may occur in long-

term HNSCC survivors. These include: speech difficulties, chronic pain, ototoxicity,
and/or peripheral or autonomic neuropathies. These are discussed below.

Speech intelligibility — Speech and articulation could be significantly impaired after

treatment for oral cavity cancer, floor of the mouth or alveolar crest cancers, cancers
requiring mandibular resection, and with total or partial glossectomy [54-56]. Voice
and phonation issues affect patients with laryngeal cancer treated with
chemoradiation and patients who have had a laryngectomy [57]. (See "Speech and
swallowing rehabilitation of the patient with head and neck cancer".)

Due to complications of total laryngectomy — Although long-term survivors

are usually acclimated to the surgical outcomes, total laryngectomy continues to
impart a high impact on quality of life of survivors even years after surgery [58].
Despite a multidisciplinary follow-up, long-term rehabilitation with these prostheses
could be difficult and require guidance and support [59]. For patients who undergo
voice rehabilitation with tracheoesophageal voice prosthesis, leakage from the site
may add to long-term morbidity [60,61].

Lack of motivation, discouragement, depression, and continued need for lifestyle

modification could have a cumulative impact on long-term survivors. Providers should
be aware of the difficulty that can be experienced postlaryngectomy and provide
continued support, counseling, and specialized care wherever needed. (See
'Psychosocial issues of the caregivers' below.)

Due to recurrent laryngeal nerve palsy — Recurrent laryngeal nerve palsy

could occur as a rare late complication of head and neck radiation (mostly reported
with conventional RT) leading to delayed mobility of vocal cord(s) and hoarseness
[62,63]. It could lead to voice strain and speech unintelligibility in survivors several
years from completion of therapy that could be frustrating. Speech rehabilitation and
Botulinum injection in the vocal cords have limited benefit with temporary results,
and lifestyle modification may be the only option in some cases [64].

Speech therapy is required to improve speech intelligibility. Advances in

reconstructive surgical techniques with tissue transfer, mandibular plates, and palatal
prosthesis have been helpful [65-67]. Voice therapy is indicated in patients with
hoarseness and problems with phonation after chemoradiation for glottic cancer [68].
Speech rehabilitation after total laryngectomy could be challenging and requires
motivation and perseverance. It could involve an artificial larynx, transesophageal
puncture, or esophageal voice production [69,70].

Chronic pain — Chronic pain (including somatic, neuropathic, and neuralgic pain)
involving the head or neck after treatment can be debilitating and is reported in some
cancer survivors over five years post-treatment [71].

Chronic pain has been known to contribute to functional limitation and employment
in survivors. In one study, nearly 40 percent of unemployed long-term survivors
reported being in chronic pain [72,73]. In another observational study, chronic
systemic symptoms, were noted in nearly 50 percent of head and neck cancer
survivors at one year post-treatment completion, such as chronic widespread pain,
fatigue, sleep disturbance, mood disorders, neuropsychiatric symptoms, and
temperature dysregulation [74].

Although there are limited data beyond five years post-treatment, in one study, nearly
18 percent of head and neck survivors complained of chronic pain as a long-term
effect of prior cancer-related treatment [17]. In this study, chronic pain, type of diet,
and dental status at one year were strongly predictive of quality of life of these
survivors at the five-year post-treatment time point. However, in a different study, the
mean chronic pain scores (measured using the Head and Neck Cancer Inventory
social disruption scores) showed there was no difference in pain scores among those
who had received chemoradiation versus surgery followed by adjuvant radiation-
based therapy [18].

Among the more recognized pain syndromes, shoulder and neck pain are two
recognizable neuropathic conditions, particularly for those who underwent a neck
dissection. Efforts to understand other specific pain predilections in long-term
survivors are ongoing.

Interventions with drugs like gabapentin and carbamazepine, utilization of pain

management services for treatment with narcotics and behavioral therapy, and
incorporation of physical therapy may all be needed for appropriate pain control.
Acupuncture has been shown to reduce pain and shoulder dysfunction after neck
dissection [75]. Long-term opioid use and dependence is a well-described
phenomenon and was noted in approximately 7 percent of long-term head and neck
cancer survivors at one year post-treatment completion [76]. (See "Cancer pain
management: Role of adjuvant analgesics (coanalgesics)", section on 'Patients with
neuropathic pain' and "Physical rehabilitation for cancer survivors" and "Overview of
the clinical uses of acupuncture" and "Cancer pain management: General principles
and risk management for patients receiving opioids".)

Ototoxicity — Both cisplatin and radiation could lead to compromise in hearing.

Cisplatin-induced ototoxicity is well-recognized and is known occur as a result of
cisplatin-induced damage of the outer hair cells of cochlea. Radiation to the cochlea
has been known to induce sensory neural hearing loss. Cisplatin given concurrently
with radiation lowers the dose of radiation that can cause hearing loss. The incidence
ranges from 20 to 40 percent at one year post-treatment with IMRT to over 40 percent
at 5 years with conventional RT [77,78]. The interindividual variation in the degree of
cisplatin-induced toxicity endured is thought to be dependent on polymorphisms in
the glutathione-S-transferases and other genetic variations [79]. For such cases,
hearing augmentation may be required to improve quality of life and functioning.
(See "Management of late complications of head and neck cancer and its treatment".)

Peripheral neuropathy — Long-term survivors may have to deal with residual

peripheral neuropathy, both from cisplatin and taxanes. Peripheral neuropathy of
some degree could be seen in over 80 percent of patients who have received 300
mg/m2 of cumulative dose of cisplatin [80]. The neuropathy usually improves over
time, but complete resolution is rarely seen [81]. No preventative strategy has been of
benefit as per an analysis [82].
Autonomic dysfunction — Autonomic dysfunction usually presents as dizziness and
near syncope, and it has been reported in long-term survivors, especially for those
who received RT to the neck [83]. RT induces inflammation of the intimal layer, which
is thought to result in fibrosis of the arterial walls of the neck. This is thought to
contribute to the stiffening of the carotid sinus baroreceptors leading to decreased
baroreceptor sensitivity, which causes blood pressure lability, including the onset of
orthostasis-like phenomenon causing near syncope or syncope like events [84].

For patients with autonomic dysfunction, baroreceptor sensitivity may be improved

with exercise, particularly in older patients with a sedentary lifestyle [84].

Musculoskeletal complications — Lymphedema involving the neck may present as a

late complication, especially in patients who underwent a neck dissection or RT. In
addition, neck stiffness is a common complaint that is encountered in clinic.

Lymphedema — Lymphedema of the neck is common, although poorly recognized

and reported [85,86]. It could occur after surgery or RT to the head and neck area.
Although lymphedema generally resolves with time, chronic lymphedema, if severe,
could lead to permanent neck stiffness and disfigurement. Edema of the larynx and
the pharynx could also be severe and cause airway obstruction and dysphagia [85,87].

Although late-onset neck lymphedema is not well-studied, it is not uncommon for

long-term head and neck survivors to present with acute lymphedema. In one study
evaluating patients with neck lymphedema, the median time to onset of symptoms
measured from the time of treatment completion was 17 months. However, the
authors did not solely evaluate long-term survivors; they included patients who
presented with neck lymphedema between 3 and 156 months (13 years) of treatment
completion [85].

Early institution of complete decongestive therapy is indicated. In our experience, it

can provide quick relief of symptoms and prevent chronic complications [88]. (See
"Clinical staging and conservative management of peripheral lymphedema", section
on 'Complete decongestive therapy'.)

Neck stiffness — In our experience, neck stiffness is one of the more common
chronic complaints of patients in long-term follow-up. Neck stiffness is usually caused
by fibrosis of the neck muscles as a result of the longstanding effects of RT and/or
neck surgery, and it is most common in patients who received both these treatment
modalities [89-91].

Neck stiffness significantly impacts quality of life among head and neck cancer
survivors [92]. Unfortunately, there are limited clinical studies addressing the
treatment of neck stiffness. Physical therapy is the standard of care. Various regimens
have been proposed, but all have demonstrated limited clinical benefit:
● Physical therapy – For patients with neck stiffness, physical therapy is useful,
even for late symptoms. Physical therapy should be pursued with a therapist
experienced in the treatment of radiation fibrosis [93].
● Botulinum toxin – As with trismus, botulinum toxin has been utilized to reduce
symptoms from radiation-induced fibrosis in long-term survivors and may be
applicable to neck stiffness, spasms, discomfort, and pain [44].
● Pravastatin – In a single-arm phase II clinical trial of pravastatin (40 mg daily for
12 months), an at least 30 percent reduction of chronic radiation-induced fibrosis
was seen in 15 of 42 patients (36 percent) [94]. Patients reported improved quality
of life and minimal toxicities (myalgias and esophagitis).
● Other treatment options include hyperbaric oxygen and vitamin E with
pentoxifylline.

Additional information about radiation-induced fibrosis is presented separately. (See

"Clinical manifestations, prevention, and treatment of radiation-induced fibrosis",
section on 'Treatment'.)

Neurocognitive effects — RT and chemoradiotherapy as components of definitive

therapy for head and neck cancer have been postulated to have effects on the central
nervous system and result in neurocognitive deficits [95].

The risk of neurocognitive impairment was prospectively studied in a cohort of 80

patients undergoing definitive treatment for nonmetastatic squamous cell carcinoma
of the head and neck and in 40 controls without cancer [96]. All patients received RT,
86 percent received systemic therapy (most with a platinum-based regimen), and 76
percent had a primary oropharyngeal carcinoma. Neurocognitive function was
assessed at baseline, 6, 12, and 24 months using a cognitive battery assessing
multiple domains. Progressive impairment in global cognitive function was observed
in 22 of 58 patients (38 percent) at 24 months, but in 0 of 40 controls (0 percent).

Despite these studies, there are limited data confirming the degree of deficit and time
to recovery. In clinical settings, it is important to take into consideration reversible
causes for decline such as depression and to discriminate verbal decline due to lack of
appropriate orodental rehabilitation from neurocognitive decline. Brain-sparing IMRT
is now being used to help reduce the cognitive decline post-head and neck cancer
therapy.

Damage to the carotid arteries — Following treatment of HNSCC, patients have an

increased risk of stroke. However, there are no screening mechanisms in place for
head and neck cancer survivors. Therefore, the prevention and management of stroke
in long-term HNSCC survivors is similar to the approach to the general population and
is discussed separately. (See "Management of late complications of head and neck
cancer and its treatment", section on 'Carotid artery injury'.)

Nephrotoxicity — Some degree of nephrotoxicity is seen in up to 30 percent of

patients treated with cisplatin [97]. Cisplatin has been known to damage the proximal
and distal tubular epithelium and collecting ducts in animals and humans [98].
Elevated creatinine levels, hypomagnesemia, hypokalemia, hypocalcemia,
occasionally sodium wasting, proteinuria, and albuminuria could all be seen in
different combinations in long-term survivors [99,100]. Fortunately, long-term follow-
up of patients exposed to cisplatin indicates that renal function remains stable or
slightly improves over time. (See "Cisplatin nephrotoxicity".)

PSYCHOSOCIAL ISSUES

Sexual dysfunction — Long-term survivors may experience difficulty with sexual

function. This may have an anatomic basis (eg, chemotherapy-induced peripheral
neuropathy) or a more complex etiology related to intimacy issues and psychologic
distress. (See "Overview of sexual dysfunction in female cancer survivors" and
"Overview of sexual dysfunction in male cancer survivors".)
Short-term studies indicate that sexual dysfunction can be an important consequence
of treatment for head and neck cancer. In a study of 262 patients with oral squamous
cell carcinoma, 34 percent did not have sex at all in the six months following
diagnosis, compared with 10 percent in the six months prior to diagnosis [101]. This
change was present in all patients, regardless of whether they had human
papillomavirus (HPV) associated disease. A persistence of dissatisfaction with sexual
function was reported in another series at 12 months after treatment [102].
Unfortunately, there is a lack of data for longer-term survivors of head and neck
squamous cell carcinoma (HNSCC).

Although sexuality is a key issue with head and neck cancer survivors, minimal
attention has been given to it over time. Alterations in self-image, disfigurement,
change in oral sensation and odor, anxiety, and depression have been thought to
contribute. Chemotherapy could lead to altered sensation, arousal, and erectile
dysfunction in men. Issues related to transmission of HPV to a spouse or partner may
add a significant burden to a relationship. A clear understanding of the issues related
to HPV and its transmission is crucial [103].

Body image issues — Facial disfigurement, loss or change of organ function, fear of
recurrence, death, and revised self-image could all prove challenging to adjustment.
Body image reintegration and adjustment are thought to happen over time and
require compassion, patience, and encouragement from the family, friends, and the
treating clinician.

In a report from a larger study of body image among 280 HNSCC patients who
underwent surgery, and who were less than one month to more than five years from
diagnosis, over 50 percent of patients reported concerns regarding body image at the
time of assessment [104]. Major issues that can lead to social avoidance include
limitations with speech and swallowing and concerns regarding appearance and
disfigurement.

Poorer quality of life scores have been reported in the setting of body image
dysfunction [105]. In another study that evaluated the aesthetics in long-term
survivors, moderate to severe pain, minimal oral intake, and being edentulous at one
year from treatment were associated with significantly low aesthetics scores at five
years [17]. In a similar report by the same group, long-term survivors who had
received chemoradiation-based therapy had better aesthetics scores than the
surgically treated group at five years from treatment [18].

Depression, anxiety, and suicide risk — Anxiety and depression are common in
head and neck cancer patients before and after completion of therapy and have been
reported in nearly 30 percent of survivors at five years from completion of therapy
[17,106]. Clinicians should regularly assess for such mental health conditions in long-
term survivors to ensure that patients receive the support necessary [6]. (See
"Patients with cancer: Clinical features, assessment, and diagnosis of unipolar
depressive disorders".)

In one study of head and neck cancer survivors, factors that predicted depression
included the presence of a tracheostomy tube or laryngeal stoma, gastrostomy tube
dependence, and continued smoking at the time of follow-up [21]. Additional studies
have identified comorbid psychiatric illness, long-term toxicity of treatment, as well as
use of alcohol and/or drugs to cope with the diagnosis as risk factors for depression
and suicide [107,108].

While several psychosocial parameters may improve with the passage of time from
diagnosis, in one study, anxiety persisted and became more pronounced in survivors
greater than five years from diagnosis [109].

Survivors of head and neck cancer have an increased rate of suicide

[107,108,110,111]. One analysis using the Surveillance, Epidemiology, and End Results
(SEER) database reported a suicide rate in this population of 63 suicides per 100,000
person-years [108]. When compared with survivors of other cancers as a whole, head
and neck cancer survivors were approximately two times more likely to commit
suicide; only pancreatic cancer survivors had a higher suicide rate than this
population.

In a prospective study of 223 consecutive patients with newly diagnosed head and
neck cancer followed for one year, 16 percent were suicidal, 0.9 percent attempted
suicide, and 0.4 percent committed suicide [107].

These studies illustrate the severity of depression and suicide, which are two of the
most concerning long-term sequelae of head and neck cancer treatment.
Employment — Over 50 percent of head and neck survivors were reported as being
disabled from disease at the two-year post-treatment time point [72,112].
Unfortunately, data are limited in longer-term survivors.

Despite this, a number of reasons have been reported for the continued disability of
HNSCC survivors, including:
● Long-term oral dysfunction, loss of appetite, deterioration in social functions, and
high anxiety levels [113]
● More advanced stage at original presentation, alcohol use, and lower educational
levels [112]
● Fatigue [72]

Survivors may also face challenges related to facial disfigurement, limitations in

speech intelligibility, dietary limitation, and rarely even dependence on enteral tube
feeding. These issues could lead to low self-esteem, lack of initiative in socializing and
competing with peers, limitations in employment opportunities, and growth at work
place. In a study of 208 head and neck cancer survivors, socioeconomic factors and
comorbidities were found to be important predictors of quality of life [114].

Psychosocial issues of the caregivers — Psychosocial adjustments of survivors and

their caregivers are intimately linked [115,116]. Active counseling of the patient and
family members during and after treatment play an important role in minimizing the
psychosocial burden and help in rehabilitation. Long-term help and support should be
provided to caregivers and family in situations where survivors have multiple long-
term complications of treatment. The care of a head and neck cancer survivor could
still be very involved in cases with feeding tube, tracheotomy, and other disabilities
like compromised speech intelligibility.

SUBSEQUENT PRIMARY CANCERS

Subsequent primary cancers have been reported in up to 20 percent of head and neck
cancer survivors and are related to smoking and alcohol exposure. For those who
develop a subsequent primary cancer, prognosis is generally poor, with a median
overall survival typically around 12 months [117]. (See "Overview of cancer
survivorship care for primary care and oncology providers", section on 'Risk of
subsequent primary cancer'.)

During the last 20 years, a clear decrease in the incidence of subsequent cancers in
primary oropharyngeal tumors has been observed. This has been associated with an
increasing incidence of human papillomavirus (HPV) associated oropharyngeal
carcinomas [118]. With emerging data about difference in sexual practices of patients
with HPV associated tumors, longitudinal follow-up is warranted [118,119].

Lifestyle modification, smoking, and alcohol cessation intervention programs are

needed to help cancer survivors reduce their risks for a second primary [9]. Patients
should be counseled for smoking and alcohol cessation routinely and aggressively.
(See 'Smoking and alcohol cessation' above.)

COORDINATION OF CARE AND SPECIALIST REFERRAL

Care must be taken to communicate the plan of care and follow-up with the general
medical provider or primary care clinician. A detailed communication of the plan of
care with the primary dentist is also essential. In a study of oncologists and primary
care physicians, the lack of clarity of who provides specific aspects of psychosocial
care to cancer survivors brought to attention the need for better survivorship care
coordination with the multidisciplinary head and neck oncology team [120].

Head and neck cancer survivors have to engage in intensive self-management

protocols for oral care; skin care; complex drug schedules and delivery; complicated
instrument care (eg, tracheostomy care and feeding tube care); and intense
rehabilitation programs like oral-dental rehabilitation, speech and swallow
rehabilitation, and occupational therapy with lymphedema management and physical
therapy. Efforts have been made to better understand, categorize, and strategize the
intensive self-management protocols to improve quality of life of head and neck
cancer survivors [121].

Post-therapy survivor care plans should be formulated to organize adequate support

and rehabilitation to the head and neck cancer survivors. A prospective, randomized,
controlled trial of the H&N Cancer Survivor Self-management Care Plan (HNCP)
involving pre- and post-intervention assessments showed improved quality of life of
the survivors with unique needs by means of a tailored self-management care plan
developed upon completion of treatment, delivered by trained oncology nurses [122].

Communications and coordination of care between the oncology team, the primary
care clinician, the dentist, and any specialists involved in the management of the
patient is recommended throughout the treatment and in the post-treatment period.
Specific efforts should be made to include caregivers and spouses in the head and
neck survivorship plans [123].

Several support groups and support sites are available to help guide head and neck
cancer survivors and their treating clinicians in the management of late treatment-
related complications [124].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Head
and neck cancer".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)
 ● Basics topics (see "Patient education: Throat cancer (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Epidemiology – There are more than half a million survivors who have been
cured of head and neck cancer in the United States. The steady increase in the
rate of head and neck cancer survivors is likely due to advances in treatment,
decrease in smoking rates, and the improved prognosis of oropharyngeal
carcinomas associated with human papillomavirus (HPV) infection. (See
'Introduction' above.)
● Prognosis – The prognosis of HNSCC depends on stage at presentation and the
site of involvement. (See 'Prognosis' above.)

• Stage I or II disease – Five-year overall survival in patients with stage I or II

disease is approximately 70 to 90 percent.

• Stage III or IV disease – The prognosis is poorer for patients who present with
more advanced (stage III or IV) disease.

• HPV associated cancer – For patients with human papillomavirus (HPV)

associated locoregionally advanced disease, long-term survival rates are
higher than those without HPV associated disease. (See "Epidemiology,
staging, and clinical presentation of human papillomavirus associated head
and neck cancer", section on 'Prognosis'.)
● Surveillance – In general, the intensity of follow-up is greatest in the first two to
four years following diagnosis, since approximately 80 to 90 percent of all
recurrences occur within this timeframe. However, patients should continue to be
followed beyond five years because of the risk of late complications, as well as
the risk of late recurrence or second malignancies. This may be especially
important for patients without human papillomavirus (HPV) associated
oropharyngeal cancers. (See 'Guidelines for follow-up, surveillance, and
secondary prevention in the long-term survivor' above.)
● Prevention of subsequent primary cancers – Survivors should be routinely
counseled for smoking and alcohol cessation, as subsequent primary cancers
 related to smoking and alcohol exposure have been reported in up to 20 percent
of head and neck cancer survivors. (See 'Subsequent primary cancers' above.)
● Oral health and dental complications – Dental care and follow-up of oral health
are very important, especially after radiation therapy to the head and neck area.
Poor oral hygiene and dental health decline could lead to significant compromise
in quality of life of the long-term head and neck cancer survivors. (See 'Dental
complications and oral health' above.)

Worsening of dental health after treatment is common and is mostly as a result

of dry mouth or "xerostomia" from head and neck radiation. (See 'Xerostomia'
above.)

Other common complications include mucosal sensitivity, malocclusion of teeth

or dental prosthesis (dentures), osteoradionecrosis, and trismus. (See
'Osteoradionecrosis' above and 'Trismus' above.)
● Dysphagia – Patients treated for HNSCC can experience dysphagia during
treatment and as both an acute and long-term complication. Even for patients
who present with longstanding dysphagia, we believe there is a role for cancer
rehabilitation, including speech and language therapists. Despite preventive
measures employed prior to and/or during treatment, 10 to 25 percent of HNSCC
survivors become feeding tube-dependent for life. (See 'Dysphagia' above.)
● Neuromuscular toxicity – Several neuromuscular complications may occur in
long-term HNSCC survivors. (See 'Neuromuscular toxicity' above.)

• Specific toxicities – These include speech difficulties, chronic pain, ototoxicity,

and/or peripheral or autonomic neuropathies.

• Management – For many of these concerns, rehabilitation that involves

speech and physical therapists is an important part of management.
● Musculoskeletal complications – Lymphedema involving the neck may present
as a late complication, especially in patients who underwent a neck dissection or
RT. (See 'Lymphedema' above.)

In addition, neck stiffness is a common complaint that is encountered in clinic.

(See 'Neck stiffness' above.)
 ● Psychosocial issues – Survivors of HNSCC are at risk for psychosocial issues
related to body image, speech unintelligibility, food-related lifestyle limitations,
and sexual health. In addition, they are at high risk for mental health disorders,
including depression, anxiety, and suicide. Fear of recurrence and fear regarding
secondary cancers add to the burden of survivorship. Clinicians should be aware
of these issues and regularly screen for them in follow-up to ensure that these
patients get the support and counseling necessary. (See 'Psychosocial issues'
above.)
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