Advancing Survivorship Care Through Research

A schematic cross-section of the head and neck, with a rainbow of colored sticks emanating from a star image in the center of the head and radiating out to various pink and purple colored globes depicting viruses associated with head and neck cancers.

Marci Nilsen, PhD, MSN, BSN, CHPN, FAAN, is an Assistant Professor at the University of Pittsburgh School of Nursing and School of Medicine within the Department of Otolaryngology. She is also the co-founder and co-director of the UPMC Head and Neck Cancer Survivorship Clinic. At the start of The Eye & Ear Foundation’s March 8th webinar, “Advancing Survivorship Care Through Research,” she said being a nurse scientist gives her a holistic view on care and translates into a patient-centered and thoughtful approach to her research. Her research and clinical practice are centered on addressing symptoms and treatment effects to improve patients’ quality of life.

Head and Neck Cancer

Head and Neck Cancer (HNC) is a collective term used to describe a number of different malignant tumors in the upper autodigestive tract. These cancers make up 4% of the cancers in the U.S. and are the seventh most common cancer globally. It is more common in men, with approximately 75% of cases occurring in males. Many present with locoregional disease, indicating the presence of a primary tumor along with involvement in the lymph nodes of the neck.

“This means many of our patients will get more than one treatment modality,” Dr. Nilsen said.

For example, a patient may have surgery first, followed by radiation. In some instances, patients will undergo non-operative treatment, such as chemotherapy and radiation given over the same period.

Human Papillomavirus/HPV

HPV is primarily associated with tumors in the oropharynx, which encompasses the tonsils, base of the tongue, and soft palate. These patients may also be diagnosed at a younger age. Fortunately, these cancers tend to have favorable outcomes, including increased survival. The bad news is that HPV is expected to see a 30% increase by 2030. “It is anticipated that most of the patients we will see in the future will have HPV-associated cancer,” Dr. Nilsen said. This will impact their care and survivorship trajectory. Due to the young diagnosis and higher cure rate, they will live longer with the side effects of their cancer and its treatment. This has people like Dr. Nilsen thinking about different ways to not just treat them but also provide care for them both in the short and long term.

Almost half a million people in the U.S. have been diagnosed with or are living with a diagnosis of HNC, and this number is expected to continue increasing.


It is important to note that not all individuals diagnosed with HNC embrace the term “survivor,” even though it is commonly used. Considering this, the concept of survivorship emphasizes the health and well-being of a person with cancer from the time of diagnosis until the end of life. It goes beyond the physical side effects of cancer and treatment. It encompasses the financial, mental, social, and emotional. Family members, friends, and caregivers are also considered part of the survivorship experience.

“As medical professionals, we’re set up well to deal with the survivor,” Dr. Nilsen said. “We are not set up as well to deal with the loved ones that come with the survivor. We need to start taking it beyond the survivor and understand that it is something experienced by both.”

There are many models of survivorship care: general, multidisciplinary, disease-specific, consultative, integrated, community generalist model, and shared care. Regardless of the model, high quality care should be the focus, with surveillance, prevention, management, and coordination as four pillars.

Late and long-term effects include:

  • Spinal accessory nerve palsy
  • Cervical dystonia/muscle spasms
  • Neuropathies
  • Shoulder dysfunction
  • Trismus
  • Dysphagia/aspiration
  • Stricture
  • Gastroesophageal reflux
  • Lymphedema
  • Fatigue
  • Altered or loss of taste
  • Hearing loss
  • Vertigo/vestibular neuropathy
  • Sleep disturbance/sleep apnea
  • Speech/voice changes
  • Hypothyroidism
  • Dental caries/periodontitis
  • Xerostomia
  • Osteonecrosis
  • Oral infections/candidiasis
  • Body and self-image issues
  • Depression/anxiety

This is not a comprehensive list. One noticeable aspect of the list is that these treatment related effects could encompass a wide range of different healthcare specialties.

The American Society of Clinical Oncology (ASCO) Expert Panel emphasized that caring for HNC survivors requires a team-based approach that includes primary care clinicians, oncology specialists, otolaryngologists, dentists, and other allied professionals.

UPMC HNC Survivorship Clinic

This multidisciplinary, disease-specific clinic was created in 2016 and stands out in comparison to others across the country. For example, patients can be seen in the clinic before the initiation of treatment, specifically radiation, rather than only being seen after treatment is completed. Survivors can be identified and referred to the Survivorship Clinic by any provider, regardless of where they received treatment. At the clinic, patients will undergo a hearing screening, nursing assessment, and a physician exam. Then they have a tailored evaluation and are provided any necessary referrals.

The clinic includes a surgeon/advanced practice provider, hearing assistant, nurses, dietician, dentist, physical therapist, and speech-language pathologist (SLP). The advantage of this clinic is that a patient can see all these providers in one location and typically with only one copay. At the end of the visit, patients receive a survivorship care summary and schedule follow ups.

Patient-reported outcomes (PROs) are part of the clinic as well; this includes questions about health literacy, quality of life, sleep, neck pain, swallowing, depression, and anxiety.

Since 2016, the clinic has had almost 5,000 visits. About 2,500 are unique patients. Taken as a whole, swallowing is the most common issue reported by patients, followed by taste, saliva, and pain. Pain has remained in the top five issues reported by survivors since the start of the clinic even though the demographics have changed a bit.


Cancer pain is common. It is estimated that upwards of 50-90% of patients with cancer will experience pain. Pain is one of the most feared cancer symptoms. Cancer pain can last past treatment – there are more than 36 chronic pain syndromes. Cancer pain has a negative impact on quality of life, and chronic cancer pain is a growing problem.

“One of the things we saw and were very interested in in the beginning of the clinic was patients’ sensation and reporting of pain in the neck,” Dr. Nilsen said, which is surprising since HNC usually involves surgery or radiation, particularly in the neck.

The reporting and description of this pain varied. Some patients say they are getting neck cramps or their neck is stiff. Some feel they constantly have a collar on or a turtleneck that is too tight.

Neck Disability

Neck disability is pain that impacts survivors or patients’ ability to conduct their everyday activities like reading, sleeping, driving, and concentration. How does this pain that they experience in their neck impact other activities and their quality of life?

When Dr. Nilsen and her team looked at the clinic’s patients, 54.2% had a neck disability. Most were in the mild-moderate group. They also looked at treatment modalities. Initially, they assumed that the more treatment patients had, the more neck disability they had. Surgery alone had the lowest probability of having a neck disability. Non-surgical treatment like chemo and radiation had a higher rate of neck disability. Surgery and adjuvant treatment patients had a four times greater risk, but it was not statistically higher than non-operative treatment.

When they took a closer look, many patients getting radiation had an effect on their skin and tissue long after treatment was completed. Patients with a neck disability even if mild to moderate had 20 points lower in physical and social emotional quality of life; neck pain was not included in this measure. “So, we know that the presence of neck pain can impact your function and quality of life,” Dr. Nilsen said.


One of the other questions the team had is if patients were having trouble moving their neck and having pain, which may cause them to not want to move their neck, what does that do to their swallowing?

What they found was the more neck pain, the more symptoms of difficulty swallowing. This increased to the point where people in the more moderate-complete group were having symptoms that started to correlate with objective changes in swallowing. This is when aspiration becomes a concern.


The team can see neck pain in patients and identify risk factors for it. They know the prevalence and the presence of co-occurring symptoms. But does pain in the neck really impact movement? They conducted a study and saw changes in velocity, and changes in specific types of movement. However, could all these issues be related to muscle, or could they be caused by changes to the bones in the neck? O answer this, they did some work with CT scans, where they found that patients did not have cervical changes to their spine. There was no obvious connection between neck disability and pain and disc changes. This has them moving toward the idea that neck disability is related to musculoskeletal changes, tissue changes, and skin changes – commonly referred to as fibrosis.

Where Do We Go Next?

Why do some patients have more pain and dysfunction and fibrosis than others? “We do know that there are some treatment modality parts that connect more radiation or fibrosis,” Dr. Nilsen said. There is not a lot of information on the biological differences that may cause the differences we see between patients.

MicroRNA and Fibrosis

A reliable biomarker to determine those at most significant risk for radiation-induced fibrosis (RIF) does not exist; however, recent studies have provided preliminary evidence that circulating microRNAs (miRNAs) may be associated with late radiation damage in mice and non-human primates. The goal is to determine if a miRNA signature consistent with RIF could be identified in HNC survivors.

Four miRNAs were uniquely differentially expressed in both the HNC patients with moderate/severe RIF. While these preliminary results are exciting, it is essential to conduct larger, more rigorous studies to determine miRNAs’ ability to predict fibrosis and to ascertain if changes can occur over time.

Fibrosis and Treatment-Related Effects

Dr. Nilsen said their central hypothesis of this ongoing study is that 1) substantial variability in RIF and co-occurring adverse treatment effects exist, 2) this variability will cluster into distinct trajectories, and 3) trajectory membership will be explained by individual (e.g. alcohol use), cancer/treatment (e.g. site) factors and miRNA variation.

If they can identify microRNAs that are drug-targetable, there may be ways to mitigate it through pharmaceuticals, but they are also exploring more focused, tailored interventions such as rehabilitation or exercises. Dr. Nilsen’s team will follow participants over two years. Recruitment is ongoing.

Another longitudinal prospective study, MyRNA-HN, will evaluate the efficacy of the miRNA-based panel to predict which patients are at highest risk of developing radiation-induced fibrosis and associated acute treatment-effect (xerostomia, trismus, lymphedema).

Even with these studies, Dr. Nilsen is thinking about what is next because they are not interventions. How can we begin to have more focused interventions?

Moving Toward Interventions

Interventions include aspects like prehabilitation, exercise, disability-focused intervention, and intervention timing. Rehabilitation is very common outside the U.S. and has been shown to improve outcomes even with a small dose. More work is being done to find out exactly what muscles are being affected in exercise; smaller muscles are also important. It is not just about range of motion but building strength and endurance.

Timing is very important, Dr. Nilsen said. Some studies have looked at moving during treatment. Is balancing that possible during radiation treatment? Patients experience a lot of symptoms including weight loss and inability to eat. What is the dosage? The amount and timing is likely important. “We need to do a better job of being proactive than we are reactive,” she said.

In addition to neck pain, patients also experience oral pain and neuropathic pain, which is a focus of Dr. Nilsen’s collaboration with neurobiologist Dr. Nicole Scheff. If providers can impact pain, maybe they can improve the mental and psychosocial outcomes.

Social Determinants of Health

Patients come to their diagnosis in a lot of different ways. “We know that social determinants of health impact outcomes for patients of all types, not just cancer,” Dr. Nilsen said. Social determinants of health include education access and quality, health care and quality, neighborhood and built environment, social and community context, and economic stability.

Area deprivation, a social determinant of health, considers the socioeconomic status of the neighborhood individuals live in. Dr. Nilsen and her team set out to determine whether a patient’s neighborhood socioeconomic condition, in terms of area deprivation, is associated with symptom burden, psychological distress (i.e. anxiety and depression), and quality of life among HNC survivors.

Compared with survivors in the most affluent areas, survivors in the most deprived areas had significantly lower physical and social-emotional quality of life, higher depression, anxiety, insomnia, and neck disability scores.

“How do we make this high-quality survivorship care accessible and equitable?” Dr. Nilsen asked. “How can we make programs and deliver care models in a way that meets the needs of patients where they’re at in an equitable fashion?”

Part of the work they are doing now involves reaching out to community providers to understand their models of care, as well as to identify barriers and facilitators to achieving or accessing some of these services. They have also started to talk about ways to proactively access the social needs of patients, like transportation. How can this be integrated in survivorship care or initial screenings? Or is it something that can be done broadly in the group of HNC? “Patients’ ability to achieve the care they need should not be dependent on their geographical location,” Dr. Nilsen said. “It should be equitable and accessible to all.”


Survivors have complex physical and psychosocial needs stemming from their treatment. An interplay of multiple factors, social determinants of health, treatment characteristics, and biology contribute to symptoms and treatment-related effects.

“In order to deliver high-quality, equitable care, we need to partner with community providers and address the social needs of our survivors,” Dr. Nilsen said.