HPV-positive oropharyngeal squamous cell carcinoma
The following case study is inspired by patient data taken directly from the HNSCC Collection within The Cancer Imaging Archive (TCIA), a service that hosts an archive of publicly accessible de-identified cancer medical images.
- Name: Ken Burns
- Gender: M
- Age: 50
- Race: Caucasian
- Cancer: Head and neck
- Type: Squamous cell carcinoma
- Cancer site: Oropharynx
- Diagnosis: Base of tongue carcinoma
- Cancer stage: IVB
- Treatment: Concurrent chemoradiotherapy
Ken is a 50 year old Caucasian man who was shaving in the bathroom one day when he noticed a swollen lump on his neck. Not thinking much of it, he decided to ignore the enlarged mass and wait for it to subside. Two weeks later, the lump was still there.
After a visit to the doctor’s office, Ken’s primary care physician asked him a series of questions regarding his medical history and daily habits. A comprehensive patient history was taken, and questions inquiring into his daily activities and recreational habits were also asked to assess possible risk factors, including recreational drug use, sexual activity including number of recent sexual partners, smoking history and alcohol consumption.
With help from his doctor, Ken estimated that his smoking activity over the years amounted to ten pack-years, and indicated that he had quit a few years ago. Ken also admitted to having multiple sexual partners over the years, though he wasn’t sure how that would help in determining his diagnosis. He had no family history of cancer, no history of recreational drug use and was not a fan of alcohol, drinking only during holidays and on special occasions.
Taking into account these findings, Ken’s primary care doctor ordered several tests and diagnostic images to be performed. A small sample of tissue was taken to check for signs of cancer and human papillomavirus (HPV). Computed tomography (CT) scans were also taken for a better picture of activity within the head and neck region.
Biopsy results showed a histology of squamous cell carcinoma from the tumor site with poorly differentiated cancer cells, and the pathology report on Ken’s HPV status came back as positive. Based on information about Ken’s updated patient history and risk factors, as well as results from diagnostic tests and imaging, ultimately a diagnosis was made for base of tongue carcinoma. The physician carefully assessed all findings and Ken’s cancer was staged as IVB with TNM of 1, 3, 0. This clinical stage at presentation is consistent with studies which have shown that HPV-positive oropharyngeal squamous cell carcinoma tumors more likely present with early T stage (i.e., T1-T2), advanced N stage (i.e., usually cystic and multi-level), and have distinct histological features showing moderate or poor tumor differentiation.1
- Pack-year is a measure of the amount of cigarettes smoked over a period of time, calculated by multiplying the number of cigarette packs smoked per day by the number of years that person has smoked
- For example, 1 pack year is equal to smoking 1 pack, i.e., 20 cigarettes, per day for 1 year, or 2 packs, i.e., 40 cigarettes, per day for half a year, and so on
- T stands for “tumor” and describes the tumor size and any cancer spread into nearby tissue
- N stands for “node” and describes cancer spread to nearby lymph nodes
- M stands for “metastasis” and describes cancer spread to other parts of the body
HEAD AND NECK CANCER
Head and neck cancer is a collective group of cancers that starts in the mouth, nose, throat, larynx, sinus, or salivary gland. These cancers account for approximately 4% of all cancers in the United States2 and about 95% of these are squamous cell carcinomas. Cancers of the head and neck can be categorized by the site in which the cancer begins: oral cavity, oropharynx, nasopharynx, hypopharynx, glottis (larynx), or sinus. In the case of Ken, the tumor is located at the base of the tongue, which is part of the oropharynx.
Head and neck cancers are more than twice as common among men as they are among women3 and diagnosed more often among people over 50 years of age. Tobacco use, heavy alcohol use, and HPV infection increase the risk of head and neck cancers.
BASE OF TONGUE CARCINOMA
Base of tongue carcinoma is a type of head and neck cancer that develops in the back third of the tongue. Most base of tongue cancers are squamous cell carcinomas which form in the thin and flat cells that line the larynx, thyroid, throat, nose, and mouth. The area of the base of tongue is part of the oropharynx, which includes the tonsils, walls of the throat, and soft palate4.
The image of the oropharynx is taken from the Bodymap VR application.
Ken, being male, middle-aged, Caucasian, HPV-positive, having a moderately high level of sexual activity with multiple partners, with histology of poorly-differentiated squamous cell carcinoma, fits the profile of a patient having characteristics consistent with HPV-positive oropharyngeal cancer:
- Male: male-to-female ratio is 2:1 for cancers of the oral cavity and oropharynx5 and at least 3:1 for HPV-associated invasive squamous cell carcinoma of the oropharynx and oral cavity6
- Age: HPV-positive oropharyngeal squamous cell carcinoma patients have a median age of diagnosis at 54 years7
- Caucasian: white males have the highest overall incidence of oral cancer among all races and ethnicity groups8, and HPV-associated oropharyngeal squamous cell carcinoma in particular primarily affects whites and men 9
- HPV-positive: HPV is a major etiologic factor associated with oropharyngeal cancer, with HPV being detected in up to 80% of oropharyngeal cancers10
- Multiple sexual partners: sexual activity involving early first sexual relations, multiple partners, or oral sex, is characteristic of HPV-positive patients who have head and neck cancer located at the base of the tongue11; also, sexual behaviors are typically associated with HPV-positive head and neck squamous cell carcinomas but not with HPV-negative head and neck squamous cell carcinomas, which are mostly caused by tobacco and alcohol use 12
- Histology: HPV-related oropharyngeal squamous cell carcinomas tend to be poorly differentiated13
After an extensive discussion on possible treatment options, Ken’s healthcare team decided to proceed with an oncologic treatment plan involving concurrent chemoradiotherapy treatment without induction chemotherapy or surgery.
Concurrent delivery of chemotherapy and radiotherapy, where ‘concurrently’ means that the two forms of treatment may overlap or occur on the same day(s); for example, at times, radiotherapy and chemotherapy are delivered on the same day, and on other days, only radiotherapy is delivered
Prior to the actual start date of initiating radiation treatment, the radiation oncologist arranged for Ken to go through a simulation process that involved placing Ken on a simulation machine, measuring his body and marking parts of immobilization devices to make sure that during actual radiotherapy, radiation beams would be delivered safely and precisely to the intended locations11. Making the appropriate preparations and mapping out exact locations of where the treatment beams would be delivered is an important step prior to proceeding with actual radiotherapy treatment.
Immobilization devices help the patient to remain in the same position for each radiation therapy session, and can include molds, casts, headrests, masks, and other devices
During simulation, a CT scan was used to capture images of Ken’s tumor and normal tissue from various angles, and specifically at areas to be treated with radiation. The radiation therapist carefully guided Ken through the simulation process to create a treatment position that was accurate, reproducible, and specific to Ken’s requirements by using a combination of immobilization devices including masks, leg molds, headrests, sponges, and pillows.12
This CT simulation process which typically takes place approximately one week prior to the first actual radiotherapy session is important for Ken’s healthcare team to be able to properly perform accurate treatment planning and calculate the exact dose of protons to be precisely delivered to the target tumor.13
The image above is taken from the Cancer Library VR, and contains image and clinical data obtained from The Cancer Imaging Archive (TCIA), HNSCC Collection19 (TCIA subject ID: HNSCC-01-0054), with anonymized patient data and de-identified radiotherapy simulation scan showing physician- and dosimetrist-contoured target and avoidance volumes.
For the chemotherapy portion of the concurrent chemoradiotherapy treatment, Ken’s physician considered various chemotherapy agents and prescribed carboplatin, an agent best indicated for Ken and commonly used concurrently with radiotherapy.
Ultimately, Ken’s treatment plan involved weekly administration of the chemotherapy agent carboplatin at a dose of AUC 2.0, given concurrently with a radiation dose of 70 Gy in 35 fractions to the tumor, taking place over a treatment period of 30 days.
By following his healthcare team’s carefully crafted concurrent chemotherapy treatment plan, Ken successfully achieved complete response. At the most recent follow-up appointment between Ken and his primary care physician, taking place just over 7 years after completing radiotherapy treatment, Ken was assessed to be alive and healthy without cancer recurrence, with a disease-free interval of over 88 months.
Ken’s healthcare team, and particularly the team in charge of Ken’s radiation treatment portion, were not all that surprised to learn about this happy outcome, as studies have shown that HPV-related oropharyngeal squamous cell carcinoma is extremely sensitive to radiation exposure and those indicated for treatment tend to be complete responders and long-term survivors.14
This positive outcome is also consistent with studies showing that, in general, treatment outcome is much better and more curable when the cancer in question is HPV-related rather than tobacco- and alcohol-related15.
In fact, throughout the visits to the doctor’s office and discussions on treatment plans, Ken often had concerns that he would not beat this cancer, or even if the cancer were treated that it would return at a later date. He found himself increasingly regretful about certain liberties he took in his personal life, such as thoughts that he should have toned down his sex life involving multiple partners.
However, Ken’s physician offered reassurance through several research studies demonstrating that being HPV-positive in his case was not actually worse than being HPV-negative. In actuality, patients with HPV-positive base of tongue cancer had a significantly better overall and disease-free survival compared to those with HPV-negative tumors16. HPV-positive oropharyngeal cancer patients have 28-80% reductions in risk of death compared to HPV-negative patients, and are relatively much more likely to have improved outcomes17.
Ken now lives with his two dogs and has, since finishing treatment, largely abstained from some of his previous hobbies and used the extra time to pursue new interests such as swimming and cycling. His advice to anyone facing a similar situation is to properly research and find an experienced physician and specialist team including radiation oncologists and radiation therapists who will be able to form an effective treatment plan and deliver the best possible care.
Patients with HPV-positive oropharyngeal squamous cell carcinoma tend to have a more favorable prognosis and quality of life than those with HPV-negative oropharyngeal squamous cell carcinoma.18
Special acknowledgement to the researchers and institutions that provided the Soft-tissue-Sarcoma collection datasets on TCIA:
Grossberg A, Mohamed A, Elhalawani H, Bennett W, Smith K, Nolan T, Chamchod S, Kantor M, Browne T, Hutcheson K, Gunn G, Garden A, Frank S, Rosenthal D, Freymann J, Fuller C.(2017). Data from Head and Neck Cancer CT Atlas. The Cancer Imaging Archive. DOI: 10.7937/K9/TCIA.2017.umz8dv6s
Grossberg A, Mohamed A, Elhalawani H, Bennett W, Smith K, Nolan T, Williams B, Chamchod S, Heukelom J, Kantor M, Browne T, Hutcheson K, Gunn G, Garden A, Morrison W, Frank S, Rosenthal D, Freymann J, Fuller C. (2018) Imaging and Clinical Data Archive for Head and Neck Squamous Cell Carcinoma Patients Treated with Radiotherapy. Scientific Data 5:180173 (2018) DOI: 10.1038/sdata.2018.173
Clark K, Vendt B, Smith K, Freymann J, Kirby J, Koppel P, Moore S, Phillips S, Maffitt D, Pringle M, Tarbox L, Prior F. (2013) The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository, Journal of Digital Imaging, 26:6 pp 1045-1057. DOI: 10.1007/s10278-013-9622-7