Oropharyngeal cancer is classified as the presence of malignant cells in the portion of the throat known as the oropharynx. This is classified as the middle of the throat and includes the tonsils, base of tongue, pharynx walls and also the soft palate.1This type of cancer is most prevalent in men of African American and Caucasian decent.2 In 2013, it is approximated that 36,000 people will be diagnosed with oropharyngeal cancer and more than 6,000 people will die.2 While there are a variety of cancerous cells found in oropharyngeal cancer, 9 out of 10 individuals who are diagnosed will suffer from squamous cell carcinoma with a majority of cases occurring in the tonsils. 2,3
Etiology:
Ashley
While the causes of this cancer are not directly known, researchers have attributed tobacco and heavily alcohol use as potential risk factors for development of the disease. The damaging effects of smoking cause the lining of the oropharynx to deteriorate and as the body works to replace these damaged cells, there is a higher risk for an abnormality to develop and multiply causing cancer. In addition to the smoking hazards, recent research indicated that alcohol consumption increases the risk of oropharyngeal cancer by more than 30%.4 Another risk factor in the development of oropharyngeal cancer includes a diet low in zinc and Vitamin A.4 These deficiencies occur often in people who don’t eat enough protein and consume alcohol often. Finally, the human papilloma virus (HPV) is another contributing risk factor especially type 16.4
Signs & Symptoms:
Amanuel
Patients with carcinoma of oropharynx present:5
- Sore throat (the most common symptom)
- Dysphagia (difficulty swallowing)
- Otalgia (ear pain) - related to anastomotictympanic nerve of Jacobson
- Trismus (uncontrolled inability to open the mouth or jaw) - late manifestation if masseter or pterygoid muscle is involved
- Mass in the cervical region
- Carcinoma of tonsil are usually ulcerated and sometimes exophytic
Diagnostic Procedures:
Amanuel
Diagnostic work-up for oropharyngeal cancer includes:5
- Complete blood counts, chemistry profiles, and urinalysis
- Physical examination: evaluation of the neck for detection of metastatic lymph nodes as well as a search for distal metastasis
- Digital examination: evaluation for submucosal involvement of glossopalatine sulcus, base of the tongue, buccal mucosa, or lateral pharyngeal wall
- Mirror or fiberoptic examination of nasopharynx, hypopharynx, and larynx: to detect tumor extension or associated pathology
- Panendoscopy: evaluation for second primaries in upper digestive tract
- Laryngoscopy
- Fine needle aspiration of palpable lymph nodes
- Imaging studies include;
Chest x-ray
Radiography of neck or mandible
Computed tomography (CT) scan
Magnetic resonance imaging (MRI)
Radionuclide bone scan (optional)
Histology:
Lindsey
-Most tumors of the oropharynx are keratinizing squamous cell carcinomas, graded I-IV depending on the degree of differentiation6
-Less common types include malignant melanomas, sarcomas, plasmacytomas and lymphomas
-Carcinomas in the faucial arch are usually keratinizing and are more differentiated than those of the tonsillar fossa
-Lymphoepithelioma is far less common in the tonsil than the nasopharynx
-Malignant lymphomas, usually non-Hodgkin's, make up 10-15% of malignant tumors of the tonsil
-Tumors of the salivary gland are not common in the tonsil or faucial arch
Lymph node drainage:
Lindsey
-Tumors of the tonsillar fossa have a high incidence of nodal metastases, about 60-70%6
-Most mets occur in subdigastric, midjugular chain and submaxillary nodes
-Only about 5-10% involve posterior cervical nodes
-Metastases in low cervical chain occur in about 5-15% of patients with upper cervical node involvement
-The incidence of metastatic nodes in the neck increase with stage
-Lymphatic progression proceeds from upper jugular to lower cervical nodes
-Contralateral lymphadenopathy in tonsillar tumors is seen in 10-15% of patients with positive ipsilateral nodes
-Retromolar trigone, tonsillar pillar and soft palate malignancies have a metastatic rate of about 45%. The most common site of nodal involvement is in the jugulodigastric nodes, and only about 10% of patients have submaxillary node involvement
-Tumors of retromolar trigone, anterior faucial pillar and soft palate do not commonly spread to posterior cervical nodes. Contralateral spread is approximately 10%
Figure 1. Reprinted from Radiation Oncology Management Decisions. 6
Metastatic spread:
Kevin
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases isn’t always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone.7
Figure 2. Reprinted from Wikipedia: The Free Encyclopedia.7
Within the oropharynx, bilateral and contralateral lymphatic spread is common; retrograde spread to retropharyngeal lymph nodes has been reported. The deeply infiltrating nature of most cancers correlates with the frequency of lymphatic metastases at presentation (80%) of patients overall, with bilateral spread in (30%).8
Grading:
Kevin
The grade of a cancer tells you what the cells look like under a microscope. The cells are graded according to how normal or abnormal they appear. There are 4 grades of the oropharyngeal cancer cells.9
Grade 1 (low grade)-the cancer cells look very much like normal oropharyngeal cells.
Grade 2 (intermediate grade)-the cancer cells look slightly different to normal oropharyngeal cells.
Grade 3 (high grade)-the cancer cells look very abnormal and not much like normal oropharyngeal cells.
Grade 4 (high grade)-the cancer cells look very different to normal oropharyngeal cells.
Differentiation means how developed or mature (differentiated) a cell is. So doctors may describe grade 1 cancer cells as well differentiated. Grade 2 cancer cells are moderately differentiated. Grade 3 cancer cells are poorly differentiated. Grade 4 cells are undifferentiated.
Staging:
Jenn
The TNM system is used to describe staging. TNM is an abbreviation for tumor (T), node (N), and metastasis.10
TX: Primary tumor cannot be assessed.
T0: No evidenceno evidence of primary tumor.
Tis: Carcinoma in situ. Very early cancer where cells are found only in one layer of tissue.
T1: Tumor that is 2 centimeters in greatest dimension.
T2: Tumor that is larger than 2 cm, but not larger than 4cm.
T3: Tumor that is larger than 4cm.
T4a: Moderately advanced, local disease. Tumor has spread to the larynx, tongue, or jawbone.
T4b: Very advanced, local disease. Tumor has spread into the nasopharynx, skull base, or nearby arteries and muscles.
NX: Regional lymph nodes cannot be evaluated.
N0: No evidence of cancer in the regional nodes.
N1: Metastasis in a single ipsilateral lymph node, < 3cm in greatest dimension.
N2: Metastasis in a single ipsilateral lymph node, >3 cm but < 6cm in greatest dimension: or in multiple lymph nodes, none >6 cm greatest dimension.
N2a: Metastasis in a single ipsilateral lymph node >3cm but < 6cm in greatest dimension.
N2b: Metastasis in multiple ipsilateral lymph nodes, none > 6cm in greatest dimension.
N2c: Metastasis in bilateral or contralateral lymph nodes, none > 6cm in greatest dimension
MX: Distant metastasis cannot be assessed.
M0: No distant metastasis.
M1: Distant metastasis.
Stage I: T1 N0 M0
Stage IIA: T2a N0 M0
Stage IIB: T1 N1 M0 or T2a N1 M0 or T2b N0-1 M0
Stage III: T1-2 N2 M0 or T3 N0-2 M0
Stage IVA: T4 N0-2 M0
Stage IVB: Any T N3 M0
Stage IVC: Any T Any N M1
Radiation side effects:
Jenn
Some side effects after radiation are:10
Xerostomia (dry mouth)
Dysphagia (difficulty swallowing)
Sore mouth and throat
Hearing loss
Trismus (difficulty opening mouth)
Laryngeal edema
Prognosis:
Rachel
5 Year Survival rates affected by:6
-Staging
-Presence of cervical lymph nodes
-Tumor extension into the base of tongue
Cancers in the base of tongue have a less favorable prognosis than cancers in the oral tongue because they are usually larger tumors at the time of diagnosis. Base of tongue tumors are more likely to have spread to neighboring structures and to spread through lymphatics by the time of diagnosis.
Treatments:
Rachel
- T1 and T2 tumors can be treated with surgery or radiation alone.6
When using radiation alone, 60-75 Gy is usually delivered to the primary tumor. 50-75 Gy is delivered to the regional nodes, depending on the level of involvement. Brachytherapy can be used to deliver an additional 25-30 Gy to the Primary tumor.
- Surgery combined with Radiation is usually done for T3 and T4 tumors.
A pre-op dose of 30- 50 Gy can be delivered to the primary tumor. This can be followed by a post-op dose of 50-60 Gy. Doses depend on the surgical margins and the level of lymph node involvement.
-Chemoradiation:
Local regional control and overall survival has been shown to improve with concurrent chemo and radiation therapy as opposed to RT by itself in locally advanced head and neck cancers.
Figure 3. Reprinted from Radiation Oncology Management Decsions.6
- Lateral ports for Tonsillar Fossa and Faucial Arch:
Post Border: mastoid tip to 1 cm above the foramen magnum, including the posterior cervical nodes. Arrows in Figure 3 are pointing to the reduced margin after 45 Gy, in order to spare the spinal cord.
Ant Border: Clinical setup. 2 cm beyond the clinical evidence of disease.
Inf Border: Thyroid notch. If there is tumor extension inferior to this, then the margin is set accordingly.
-AP/PA port for Tonsillar Fossa and Faucial Arch:
A midline block is used to shield the larynx and part of the spinal cord, depending on level of nodal involvement.
Figure 4. Reprinted from Radiation Oncology Management Decsions.6
- Lateral ports for Base of tongue: Figure 4
Post Border: posterior cervical triangle
Ant Border: faucial arch and part of the oral tongue
Inferior Border: supraglottic larynx
Superior Border: base of skull and floor of the sphenoid sinus.
-AP/PA port for Base of Tongue:
Use a midline block to shield the larynx and part of the spinal cord. This also depends on the amount of nodal involvement.
-IMRT:
IMRT requires that the primary tumor receive a minimum of 70 Gy
Nonpalpable nodes or low risk areas should receive 54 Gy.
-Beam Energy:
4 MV or 6 MV photons
12-20 MeV electrons can be used for a boost, especially if the tumor is more laterally located.
9 MeV is best for boosting the posterior cervical nodes. This keeps the spinal canal from recieving high doses.
TD 5/5:
Brandon
TD 5/5: Total dose delivered by a standard fractionation schedule that causes a minimal (5%) complication rate within 5 years.11
Epidemiolgy:
Ashley
Oropharyngeal cancer is classified as the presence of malignant cells in the portion of the throat known as the oropharynx. This is classified as the middle of the throat and includes the tonsils, base of tongue, pharynx walls and also the soft palate.1 This type of cancer is most prevalent in men of African American and Caucasian decent.2 In 2013, it is approximated that 36,000 people will be diagnosed with oropharyngeal cancer and more than 6,000 people will die.2 While there are a variety of cancerous cells found in oropharyngeal cancer, 9 out of 10 individuals who are diagnosed will suffer from squamous cell carcinoma with a majority of cases occurring in the tonsils. 2,3
Etiology:
Ashley
While the causes of this cancer are not directly known, researchers have attributed tobacco and heavily alcohol use as potential risk factors for development of the disease. The damaging effects of smoking cause the lining of the oropharynx to deteriorate and as the body works to replace these damaged cells, there is a higher risk for an abnormality to develop and multiply causing cancer. In addition to the smoking hazards, recent research indicated that alcohol consumption increases the risk of oropharyngeal cancer by more than 30%.4 Another risk factor in the development of oropharyngeal cancer includes a diet low in zinc and Vitamin A.4 These deficiencies occur often in people who don’t eat enough protein and consume alcohol often. Finally, the human papilloma virus (HPV) is another contributing risk factor especially type 16.4
Signs & Symptoms:
Amanuel
Patients with carcinoma of oropharynx present:5
- Sore throat (the most common symptom)
- Dysphagia (difficulty swallowing)
- Otalgia (ear pain) - related to anastomotictympanic nerve of Jacobson
- Trismus (uncontrolled inability to open the mouth or jaw) - late manifestation if masseter or pterygoid muscle is involved
- Mass in the cervical region
- Carcinoma of tonsil are usually ulcerated and sometimes exophytic
Diagnostic Procedures:
Amanuel
Diagnostic work-up for oropharyngeal cancer includes:5
- Complete blood counts, chemistry profiles, and urinalysis
- Physical examination: evaluation of the neck for detection of metastatic lymph nodes as well as a search for distal metastasis
- Digital examination: evaluation for submucosal involvement of glossopalatine sulcus, base of the tongue, buccal mucosa, or lateral pharyngeal wall
- Mirror or fiberoptic examination of nasopharynx, hypopharynx, and larynx: to detect tumor extension or associated pathology
- Panendoscopy: evaluation for second primaries in upper digestive tract
- Laryngoscopy
- Fine needle aspiration of palpable lymph nodes
- Imaging studies include;
Chest x-ray
Radiography of neck or mandible
Computed tomography (CT) scan
Magnetic resonance imaging (MRI)
Radionuclide bone scan (optional)
Histology:
Lindsey
-Most tumors of the oropharynx are keratinizing squamous cell carcinomas, graded I-IV depending on the degree of differentiation6
-Less common types include malignant melanomas, sarcomas, plasmacytomas and lymphomas
-Carcinomas in the faucial arch are usually keratinizing and are more differentiated than those of the tonsillar fossa
-Lymphoepithelioma is far less common in the tonsil than the nasopharynx
-Malignant lymphomas, usually non-Hodgkin's, make up 10-15% of malignant tumors of the tonsil
-Tumors of the salivary gland are not common in the tonsil or faucial arch
Lymph node drainage:
Lindsey
-Tumors of the tonsillar fossa have a high incidence of nodal metastases, about 60-70%6
-Most mets occur in subdigastric, midjugular chain and submaxillary nodes
-Only about 5-10% involve posterior cervical nodes
-Metastases in low cervical chain occur in about 5-15% of patients with upper cervical node involvement
-The incidence of metastatic nodes in the neck increase with stage
-Lymphatic progression proceeds from upper jugular to lower cervical nodes
-Contralateral lymphadenopathy in tonsillar tumors is seen in 10-15% of patients with positive ipsilateral nodes
-Retromolar trigone, tonsillar pillar and soft palate malignancies have a metastatic rate of about 45%. The most common site of nodal involvement is in the jugulodigastric nodes, and only about 10% of patients have submaxillary node involvement
-Tumors of retromolar trigone, anterior faucial pillar and soft palate do not commonly spread to posterior cervical nodes. Contralateral spread is approximately 10%
Metastatic spread:
Kevin
Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases isn’t always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone.7
Within the oropharynx, bilateral and contralateral lymphatic spread is common; retrograde spread to retropharyngeal lymph nodes has been reported. The deeply infiltrating nature of most cancers correlates with the frequency of lymphatic metastases at presentation (80%) of patients overall, with bilateral spread in (30%).8
Grading:
Kevin
The grade of a cancer tells you what the cells look like under a microscope. The cells are graded according to how normal or abnormal they appear. There are 4 grades of the oropharyngeal cancer cells.9
Grade 1 (low grade)-the cancer cells look very much like normal oropharyngeal cells.
Grade 2 (intermediate grade)-the cancer cells look slightly different to normal oropharyngeal cells.
Grade 3 (high grade)-the cancer cells look very abnormal and not much like normal oropharyngeal cells.
Grade 4 (high grade)-the cancer cells look very different to normal oropharyngeal cells.
Differentiation means how developed or mature (differentiated) a cell is. So doctors may describe grade 1 cancer cells as well differentiated. Grade 2 cancer cells are moderately differentiated. Grade 3 cancer cells are poorly differentiated. Grade 4 cells are undifferentiated.
Staging:
Jenn
The TNM system is used to describe staging. TNM is an abbreviation for tumor (T), node (N), and metastasis.10
TX: Primary tumor cannot be assessed.
T0: No evidenceno evidence of primary tumor.
Tis: Carcinoma in situ. Very early cancer where cells are found only in one layer of tissue.
T1: Tumor that is 2 centimeters in greatest dimension.
T2: Tumor that is larger than 2 cm, but not larger than 4cm.
T3: Tumor that is larger than 4cm.
T4a: Moderately advanced, local disease. Tumor has spread to the larynx, tongue, or jawbone.
T4b: Very advanced, local disease. Tumor has spread into the nasopharynx, skull base, or nearby arteries and muscles.
NX: Regional lymph nodes cannot be evaluated.
N0: No evidence of cancer in the regional nodes.
N1: Metastasis in a single ipsilateral lymph node, < 3cm in greatest dimension.
N2: Metastasis in a single ipsilateral lymph node, >3 cm but < 6cm in greatest dimension: or in multiple lymph nodes, none >6 cm greatest dimension.
N2a: Metastasis in a single ipsilateral lymph node >3cm but < 6cm in greatest dimension.
N2b: Metastasis in multiple ipsilateral lymph nodes, none > 6cm in greatest dimension.
N2c: Metastasis in bilateral or contralateral lymph nodes, none > 6cm in greatest dimension
MX: Distant metastasis cannot be assessed.
M0: No distant metastasis.
M1: Distant metastasis.
Stage I: T1 N0 M0
Stage IIA: T2a N0 M0
Stage IIB: T1 N1 M0 or T2a N1 M0 or T2b N0-1 M0
Stage III: T1-2 N2 M0 or T3 N0-2 M0
Stage IVA: T4 N0-2 M0
Stage IVB: Any T N3 M0
Stage IVC: Any T Any N M1
Radiation side effects:
Jenn
Some side effects after radiation are:10
Xerostomia (dry mouth)
Dysphagia (difficulty swallowing)
Sore mouth and throat
Hearing loss
Trismus (difficulty opening mouth)
Laryngeal edema
Prognosis:
Rachel
5 Year Survival rates affected by:6
-Staging
-Presence of cervical lymph nodes
-Tumor extension into the base of tongue
Cancers in the base of tongue have a less favorable prognosis than cancers in the oral tongue because they are usually larger tumors at the time of diagnosis. Base of tongue tumors are more likely to have spread to neighboring structures and to spread through lymphatics by the time of diagnosis.
Treatments:
Rachel
- T1 and T2 tumors can be treated with surgery or radiation alone.6
When using radiation alone, 60-75 Gy is usually delivered to the primary tumor. 50-75 Gy is delivered to the regional nodes, depending on the level of involvement. Brachytherapy can be used to deliver an additional 25-30 Gy to the Primary tumor.
- Surgery combined with Radiation is usually done for T3 and T4 tumors.
A pre-op dose of 30- 50 Gy can be delivered to the primary tumor. This can be followed by a post-op dose of 50-60 Gy. Doses depend on the surgical margins and the level of lymph node involvement.
-Chemoradiation:
Local regional control and overall survival has been shown to improve with concurrent chemo and radiation therapy as opposed to RT by itself in locally advanced head and neck cancers.
- Lateral ports for Tonsillar Fossa and Faucial Arch:
Post Border: mastoid tip to 1 cm above the foramen magnum, including the posterior cervical nodes. Arrows in Figure 3 are pointing to the reduced margin after 45 Gy, in order to spare the spinal cord.
Ant Border: Clinical setup. 2 cm beyond the clinical evidence of disease.
Inf Border: Thyroid notch. If there is tumor extension inferior to this, then the margin is set accordingly.
-AP/PA port for Tonsillar Fossa and Faucial Arch:
A midline block is used to shield the larynx and part of the spinal cord, depending on level of nodal involvement.
- Lateral ports for Base of tongue: Figure 4
Post Border: posterior cervical triangle
Ant Border: faucial arch and part of the oral tongue
Inferior Border: supraglottic larynx
Superior Border: base of skull and floor of the sphenoid sinus.
-AP/PA port for Base of Tongue:
Use a midline block to shield the larynx and part of the spinal cord. This also depends on the amount of nodal involvement.
-IMRT:
IMRT requires that the primary tumor receive a minimum of 70 Gy
Nonpalpable nodes or low risk areas should receive 54 Gy.
-Beam Energy:
4 MV or 6 MV photons
12-20 MeV electrons can be used for a boost, especially if the tumor is more laterally located.
9 MeV is best for boosting the posterior cervical nodes. This keeps the spinal canal from recieving high doses.
TD 5/5:
Brandon
TD 5/5: Total dose delivered by a standard fractionation schedule that causes a minimal (5%) complication rate within 5 years.11
Oral Cavity: 6000 cGy - Ulceration
Spinal Cord: 4500 cGy - Necrosis / Myelitis
Parotid Glands: 3200 cGy - Xerostomia
References:
Oropharyngeal Cancer Overview. Cleveland Clinic Website. http://my.clevelandclinic.org/disorders/oropharyngeal_cancer/hic_oropharyngeal_cancer.aspx. Updated January 29, 2013. Accessed May 28, 2013.
Oral and Ororpharyngeal Cancer. American Cancer Society Website. http://www.cancer.org/cancer/oralcavityandoropharyngealcancer/detailedguide. Updated February 26, 2013. Accessed May 28, 2013.
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 724.
Definite risks for mouth and oropharyngeal cancer. Cancer Research UK Website. http://www.cancerresearchuk.org/cancer-help/type/mouth-cancer/about/risks/definite-risks-for-mouth-and-oropharyngeal-cancer. Updated March 19, 2013. Accessed May 31, 2013.
Perez CA, Halperin EC, Brady LW. Principle & Practice of Radiation Oncology. 4th ed.Philadelphia, PA. Lippincott Williams &Wilkins; 2004: 1189-1190.
Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 259-268.
Metastasis-Wikipedia, the free encyclopedia. Available at http://www.wikipedia.org/wiki/Metastasis. Accessed on May 28, 2013.
Cancer research UK. Grade and stage of mouth cancer. Available at http://www.cancerresearchuk.org/cancer.../grade-and-stage-of-mouth-cancers. Accessed May 28, 2013.
National Cancer Institute. Metastatic Cancer Fact Sheet. Available at http://www.cancer.gov/cancertopics/factsheet/sites-types/metastatic. Accessed May 29, 2013.
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO.Mosby Elsevier; 2010: 708-710
Washington C, Leaver D. Principles and Practice of Radiation Oncology. 3rd ed. St. Louis, MO. Mosby Elsevier; 2010: 80-82.
Back to Week 1