Guideline sources The following summarized guidelines for the evaluation and management of oropharyngeal cancer (OPC) are prepared by our editorial team based on guidelines from the American Society of Clinical Oncology (ASCO 2022; 2019; 2018), the European Society for Radiotherapy and Oncology (ESTRO/EHNS/ESMO 2020), the American College of Radiology (ACR 2019), the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF 2017), the American Society for Radiation Oncology (ASTRO 2017), the American Cancer Society (ACS 2016), and the United Kingdom National Multidisciplinary Guidelines (UKNMG 2016). 1 2 3 4 5 6 7 8 9 Calculator Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s TNM class https://web.pathway.md/diseases/reccEoLiYU26ZH7od 1/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Guidelines 1. Classification and risk stratification Staging: use the UICC TNM system for staging. 2. Diagnostic investigations History and physical examination: As per EHNS 2020 guidelines, obtain a clinical assessment in patients with suspected OPC. B As per AAO-HNSF 2017 guidelines, elicit an initial history and perform a physical examination in adult patients with a neck mass to identify suspicious findings representing an increased risk for malignancy. B Show 4 more Diagnostic imaging: As per EHNS 2020 guidelines, perform rigid head and neck endoscopy, obtain contrast- enhanced head and neck CT and/or MRI, and chest imaging (CT and/or 18F-FDG-positron emission tomography) in patients with suspected head and neck cancer. B As per ACR 2019 guidelines: Obtain contrast-enhanced neck CT or MRI for the initial imaging of nonpulsatile neck masses (not in the parotid region or thyroid). B Obtain contrast-enhanced neck CT or MRI or neck ultrasound for the initial imaging of neck masses (not in the parotid region or thyroid) in pediatric patients. B As per AAO-HNSF 2017 guidelines, obtain contrast-enhanced neck CT (or MRI) in patients with a neck mass deemed at increased risk for malignancy. B As per UKNMG 2016 guidelines, obtain cross-sectional imaging in all patients to complete assessment and staging. Obtain MRI of the primary site and CT of the neck and chest. B 3. Diagnostic procedures Fine-needle aspiration: Perform FNA instead of open biopsy in patients with a neck mass of uncertain diagnosis deemed at increased risk for malignancy. B Continue evaluating patients with a cystic neck mass, as determined by FNA or imaging, until a diagnosis is obtained instead of assuming that the mass is benign. B Tumor biopsy: As per EHNS 2020 guidelines: Perform a pathological examination for diagnostic confirmation of OPC. B https://web.pathway.md/diseases/reccEoLiYU26ZH7od 2/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Evaluate the depth of invasion of oral cavity cancer, assess the number of invaded lymph nodes and the presence of extracapsular extension, perineural and lymphatic infiltration, and the surgical margins on the surgical specimens. A As per AAO-HNSF 2017 guidelines, evaluate the upper aerodigestive tract under anesthesia before performing an open biopsy in patients with a neck mass deemed at increased risk for malignancy and without a diagnosis or primary site identified with FNA, imaging, and/or ancillary tests. B Immunohistochemistry and mutational testing: As per ASCO 2022 guidelines: Obtain PD-L1 immunohistochemistry testing in patients with recurrent or metastatic head and neck SCC. Interpret PD-L1 CPS 1 as positive, recognizing that it correlates with a clinical benefit to PD-L1 inhibitors. A Consider obtaining tumor mutational burden testing in patients with recurrent or metastatic head and neck SCC when CPS is unavailable or in patients with rare tumors. Interpret tumor mutational burden 10 as high, recognizing that it correlates with a clinical benefit to PD-L1 inhibitors. B As per EHNS 2020 guidelines: Assess the p16 status in patients with OPC. A Assess for p16 and Epstein-Barr-encoded RNA in patients with head and neck SCC of unknown primary. Obtain another specific HPV testing to confirm the HPV status if p16 staining is positive. B Assess for PD-L1 expression in patients with recurrent and/or metastatic head and neck SCC. B HPV testing: obtain high-risk HPV testing (on the primary tumor or on a regional lymph node metastasis when the clinical findings are consistent with an oropharyngeal primary) in all patients with newly diagnosed oropharyngeal SCC, including all histologic subtypes. E Show 11 more 4. Medical management General principles: manage patients with OPC at high-volume facilities. B Show 3 more Management of locoregional disease: As per EHNS 2020 guidelines, treat early disease as much as possible with a single-modality treatment. B Show 5 more As per ASCO 2019 guidelines, do not offer adjuvant neck radiotherapy in patients with pathologically node-negative (pN0) or a single pathologically positive node (pN1) without extranodal extension after high-quality neck dissection, unless there are indications from the primary tumor characteristics, such as perineural invasion, lymphovascular space invasion, or a T3/4 primary. D https://web.pathway.md/diseases/reccEoLiYU26ZH7od 3/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Show 6 more As per ASTRO 2017 guidelines, do not offer routine induction chemotherapy in patients with oropharyngeal SCC. D Show 15 more Management of advanced/metastatic disease: As per ASCO 2022 guidelines, offer pembrolizumab monotherapy or pembrolizumab, platinum, and fluorouracil as first-line therapy in patients with metastatic head and neck SCC with a CPS 1. A Consider offering pembrolizumab, platinum, and fluorouracil as first-line therapy in patients with metastatic head and neck SCC with a CPS < 1. B Show 3 more As per EHNS 2020 guidelines, offer pembrolizumab in combination with platinum/5-fluorouracil or pembrolizumab monotherapy in patients with metastatic head and neck SCC expressing PD- L1 (CPS 1). Offer chemotherapy plus pembrolizumab when rapid tumor shrinkage is needed. A Show 2 more As per ASTRO 2017 guidelines, offer concurrent high-dose intermittent cisplatin in patients with stage IVA-B oropharyngeal SCC receiving definitive radiotherapy. A Show 3 more Management of recurrent disease: As per ASCO 2022 guidelines, offer pembrolizumab monotherapy or pembrolizumab, platinum, and fluorouracil as first-line therapy in patients with recurrent head and neck SCC with a CPS 1. A Consider offering pembrolizumab, platinum, and fluorouracil as first-line therapy in patients with recurrent head and neck SCC with a CPS < 1. B Show 2 more As per EHNS 2020 guidelines, offer pembrolizumab in combination with platinum/5-fluorouracil or pembrolizumab monotherapy in patients with recurrent head and neck SCC expressing PD- L1 (CPS 1). Offer chemotherapy plus pembrolizumab when rapid tumor shrinkage is needed. A Show 2 more 5. Therapeutic procedures Technical considerations for radiotherapy (modality): use intensity-modulated radiotherapy or volumetric-modulated arc therapy for radiotherapy. A Technical considerations for radiotherapy (dosing, definitive therapy): administer standard once-daily definitive radiotherapy at a dose of 70 Gy over 7 weeks to gross primary and nodal disease in patients with stage III-IV oropharyngeal SCC. B Show 6 more Technical considerations for radiotherapy (dosing, adjuvant therapy): https://web.pathway.md/diseases/reccEoLiYU26ZH7od 4/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Administer adjuvant postoperative radiotherapy at a total dose of 60-66 Gy in 2-Gy once-daily fractions to regions of microscopically positive primary site surgical margins and extracapsular nodal extension, B including patients not receiving concurrent systemic therapy. B Administer adjuvant postoperative radiotherapy at a total dose of at least 60 Gy in 2-Gy once- daily fractions to the tumor bed, and involved, dissected lymph node regions in the absence of primary site positive margins and extracapsular nodal extension. B Technical considerations for radiotherapy (radiosensitizer): use a hypoxic radiosensitizer agent to increase locoregional control and disease-free survival. A 6. Surgical interventions Indications for neck dissection (primary surgery): perform an ipsilateral elective neck dissection in patients with stage cT2-cT4, cN0 oropharyngeal SCC (no clinical or radiographic evidence of metastatic spread to the neck) treated with curative-intent surgery. A Show 9 more Indications for neck dissection, post-treatment surgery: As per ESTRO/ESMO/EHNS 2020 guidelines, do not perform neck dissection in patients with negative 18F-FDG-positron emission tomography and normal-sized lymph nodes at 12 weeks post-chemoradiotherapy. D As per ASCO 2019 guidelines, perform neck dissection, if feasible, in patients with intense FDG uptake in any node on positron emission tomography/CT at 12 weeks after completion of radiotherapy/chemoradiotherapy. A Show 3 more 7. Specific circumstances Patients with tonsillar cancer: Offer unilateral radiotherapy in patients with well-lateralized (confined to tonsillar fossa) T1-T2 tonsillar cancer and N0-N1 nodal category. B Consider offering unilateral radiotherapy in patients with lateralized (< 1 cm of soft palate extension but without base of tongue involvement) T1-T2N0-N2a tonsillar cancer without clinical or radiographic evidence of extracapsular extension, after careful discussion of patient preferences and the relative benefits of unilateral treatment versus the potential for contralateral nodal recurrence and subsequent salvage treatment. C 8. Follow-up and surveillance Serial clinical assessment: educate and counsel all head and neck cancer survivors about the signs and symptoms of local recurrence. B Show 4 more https://web.pathway.md/diseases/reccEoLiYU26ZH7od 5/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Serial endoscopic assessment: obtain clinical follow-up with head and neck examination by flexible endoscopy every 2-3 months during the first 2 years, every 6 months for years 3-5, and annually thereafter. B Serial imaging assessment: As per EHNS 2020 guidelines: Obtain FDG-positron emission tomography/CT 3 months after chemoradiotherapy to assess the necessity of neck dissection in patients with node-positive disease. A Obtain imaging if symptoms occur or in cases of abnormalities found at the clinical examination. B As per UKNMG 2016 guidelines, obtain positron emission tomography-CT for the assessment of response to chemoradiotherapy and recurrence. B Survivorship and rehabilitation (lifestyle modifications): advise achieving and maintaining a healthy weight in head and neck cancer survivors, B including offering nutrition strategies to maintain a healthy weight if at risk for cachexia. B Advise limiting consumption of high-calorie foods and beverages and increase physical activity to promote and maintain weight loss if overweight or obese. A Show 4 more Survivorship and rehabilitation (neuromuscular complications): refer patients with spinal accessory nerve palsy occurring after radical neck dissection to a rehabilitation specialist to improve their ROM and ability to perform daily tasks. A Show 3 more Survivorship and rehabilitation (neurosensory complications): Refer patients with altered or loss of taste to a registered dietitian for dietary counseling and assistance in additional seasoning of food, avoiding unpleasant food, and expanding dietary options. B Refer patients to appropriate specialists (audiologists) for loss of hearing, vertigo, or vestibular neuropathy related to treatment. B Survivorship and rehabilitation (speech disturbance): assess patients for speech disturbance B and refer to an experienced speech-language pathologist if a communication disorder is present. B Survivorship and rehabilitation (oral and dental care): advise maintaining regular dental care, including frequent visits to dental professionals, early interventions for dental complications, and meticulous oral hygiene. Test fitting dentures to ensure proper fit and advise removing them at night to avoid irritation. B Show 9 more Survivorship and rehabilitation (gastroesophageal complications): refer patients with complaints of dysphagia, postprandial cough, unexplained weight loss, or pneumonia to an experienced speech-language pathologist for instrumental evaluation of swallowing function to assess and manage dysphagia and possible aspiration. Recognize the potential for psychosocial barriers to swallowing recovery and refer to an appropriate clinician if barriers are present. Refer https://web.pathway.md/diseases/reccEoLiYU26ZH7od 6/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway patients to a speech-language pathologist for videofluoroscopy as the first-line test in patients with suspected stricture due to the high degree of coexisting physiologic dysphagia. B Show 2 more Survivorship and rehabilitation (thyroid dysfunction): measure TSH every 6-12 months to monitor thyroid function in head and neck cancer survivors. B Survivorship and rehabilitation (lymphedema): use the National Cancer Institute Common Toxicity Criteria for Adverse Events v.4.03 or refer for endoscopic evaluation of mucosal edema of the oropharynx and larynx, tape measurements, ultrasound, or external photographs for the assessment of lymphedema. Refer patients to a rehabilitation specialist for treatment consisting of manual lymphatic drainage and, if tolerated, compressive bandaging. B Survivorship and rehabilitation (fatigue): Assess for fatigue and treat any causative factors, including anemia, thyroid dysfunction, and cardiac dysfunction. B Offer treatment for factors that may impact fatigue, such as mood disorders, sleep disturbance, and pain, in patients without an otherwise identifiable cause of fatigue. A Advise regular physical activity and offer CBT as appropriate. A Survivorship and rehabilitation (sleep disorders): ask patients and their partners about snoring and symptoms of sleep apnea to screen for sleep disturbance. Refer patients with suspected sleep apnea to a sleep specialist for a sleep study (polysomnography). B Show 2 more Survivorship and rehabilitation (psychosocial distress): assess head and neck cancer survivors for body and self-image concerns. Refer for psychosocial care as indicated. A Show 3 more Clinical findings Symptoms Past medical history Anxiety Depression Change in voice Erythroplakia Dysarthria Fanconi anemia Dysphagia HPV infection Ear pain Immunocompromising condition Globus sensation Leukoplakia Hemoptysis Lichen planus Odynophagia Neurological exam Throat pain Tongue pain Speech disturbance Weight loss Lymphatic exam Social history Cervical lymphadenopathy https://web.pathway.md/diseases/reccEoLiYU26ZH7od 7/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway Alcohol consumption Betel nut chewing Exposure to excessive sun Tobacco use Head and neck exam Neck mass Oral mass Oral plaque Oral ulcers References 1. J P Machiels, C Ren Leemans, W Golusinski et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS ESMO ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31 11 1462 1475. Open 2. Ezra E W Cohen, Samuel J LaMonte, Nicole L Erb et al. American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016 May;66 3 203 39. Open 3. Emrullah Yilmaz, Nofisat Ismaila, Julie E Bauman et al. Immunotherapy and Biomarker Testing in Recurrent and Metastatic Head and Neck Cancers: ASCO Guideline. J Clin Oncol. 2023 Feb 10;41 5 1132 1146. Open 4. Melissa A Pynnonen, M Boyd Gillespie, Benjamin Roman et al. Clinical Practice Guideline: Evaluation of the Neck Mass in Adults. Otolaryngol Head Neck Surg. 2017 Sep;157 2_suppl):S1 S30. Open 5. H Mehanna, M Evans, M Beasley et al. Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016 May;130 S2 S90 S96. Open 6. Sher DJ, Adelstein DJ, Bajaj GK et al. Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline. Pract Radiat Oncol. 2017 Jul Aug;7 4 246 253. Open 7. Shlomo A Koyfman, Nofisat Ismaila, Doug Crook et al. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. J Clin Oncol. 2019 Jul 10;37 20 1753 1774. Open 8. Carole Fakhry, Christina Lacchetti, Lisa M Rooper et al. Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J Clin Oncol. 2018 Nov 1;36 31 3152 3161. Open 9. Expert Panel on Neurologic Imaging:, Joseph M Aulino, Claudia F E Kirsch et al. ACR Appropriateness Criteria Neck Mass-Adenopathy. J Am Coll Radiol. 2019 May;16 5S S150 S160. Open 10. Moyer VA, . Screening for oral cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014 Jan 7;160 1 55 60. Open 11. Ellie Maghami, Nofisat Ismaila, Adriana Alvarez et al. Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline. J Clin Oncol. 2020 Aug 1;38 22 2570 2596. Open https://web.pathway.md/diseases/reccEoLiYU26ZH7od 8/9 6/30/23, 1:23 AM Oropharyngeal cancer Pathway 12. Maria K. Gule-Monroe, MDa, Susana Calle et al. ACR Appropriateness Criteria Staging and Post- Therapy Assessment of Head and Neck Cancer. ACR. 2023. Open https://web.pathway.md/diseases/reccEoLiYU26ZH7od 9/9