INTRODUCTION — Oropharyngeal squamous cell carcinoma (OPSCC) arises in the soft palate, tonsils, base of tongue, pharyngeal wall, or vallecula, the fold located between the base of tongue and the epiglottis (figure 1) [1].
An overview of the treatment of locoregionally advanced (generally, stage III and IV) oropharyngeal cancer will be reviewed here. (See 'Definition' below.)
The clinical presentation of oropharyngeal cancer, the treatment of early (stage I and II) oropharyngeal cancer, the treatment of human papillomavirus (HPV) associated oropharyngeal cancer, and the management of metastatic and recurrent head and neck cancer is discussed separately.
●(See "Treatment of human papillomavirus associated oropharyngeal cancer".)
●(See "Treatment of metastatic and recurrent head and neck cancer".)
DEFINITION — The eighth edition tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) is used to stage oropharyngeal carcinoma. Separate staging systems have been established for human papillomavirus (HPV) associated (p16 positive) oropharyngeal carcinoma (table 1A-B) and for non-HPV associated (p16 negative) oropharyngeal cancer (table 2A-B) [2,3]. (See "Overview of the diagnosis and staging of head and neck cancer".)
Locoregionally advanced oropharyngeal cancers are generally larger primary tumors (T3 or T4) with or without lymph node involvement (figure 2) or smaller primary tumors (T1 or greater) with lymph node involvement, but without distant metastases.
EPIDEMIOLOGY AND RISK FACTORS — The epidemiology and risk factors for human papillomavirus (HPV) associated and non-HPV associated oropharyngeal squamous cell carcinoma (OPSCC (table 3)) are discussed separately. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer", section on 'Epidemiology' and "Treatment of early (stage I and II) head and neck cancer: The oropharynx", section on 'Epidemiology and risk factors'.)
MANAGEMENT
Nonsurgical versus surgical approaches — The treatment of locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC; regardless of human papillomavirus [HPV] status) may include surgery and radiation therapy (RT), either as single modalities or in combination. For medically fit patients where surgery would result in significant postoperative functional morbidity, chemotherapy can be administered concurrently (or sequentially, in some cases) with radiation as an alternative to surgery, with the goal of organ function preservation. The optimal treatment requires a multidisciplinary team approach from a head and neck surgeon, radiation oncologist, and medical oncologist, among other clinicians [4]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)
For all patients with OPSCC, regardless of HPV tumor status, when selecting between a nonsurgical approach (eg, RT with or without chemotherapy) and primary surgery (eg, transoral robotic surgery [TORS], transoral laser microsurgery [TLM], or more extensive resection techniques), discretion must be used to optimize efficacy, reduce risks of long-term toxicity, and preserve basic oropharyngeal function (eg, swallowing and airway protection). This is especially true for patients with HPV associated tumors, who have a greater likelihood of long-term survival following curative-intent therapy compared with those who have non-HPV associated disease. Clinical trials investigating treatment deintensification in HPV associated oropharyngeal carcinoma are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Is there a role for treatment deintensification?'.)
Nonsurgical approaches are more common in patients with locoregionally advanced OPSCC. However, surgery followed by either postoperative (adjuvant) RT or concurrent chemoradiation is a reasonable alternative in appropriately selected patients. A systematic review of 44 observational studies suggested comparable survival outcomes between TORS and RT, but improved functional outcomes with TORS [5]. However, the functional outcome results were likely biased given that no randomized trials were included, and most patients treated with TORS were selected for earlier stage disease compared with those treated with RT.
Surgical and nonsurgical approaches have subsequently been compared in randomized studies of patients with locoregionally advanced OPSCC, which are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Surgical resection'.)
The selection of therapy for patients with locoregionally advanced HPV associated OPSCC (algorithm 1) is discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Locoregionally advanced disease'.)
Nonsurgical approaches (functional organ preservation)
Patient selection (nonsurgical approaches) — For patients with locoregionally advanced (stage III and IV) OPSCC, nonsurgical approaches that include radiation therapy (RT) usually with chemotherapy are frequently used. However, surgical approaches remains an option in carefully selected patients where postoperative functional morbidity is predicted be minimal. These and other situations where a surgical approach may be indicated are discussed below. (See 'Patient selection (surgery)' below.)
Situations where a nonsurgical approach may be favored include the following:
●Unresectable disease – Some patients are determined preoperatively to have unresectable disease. Others who are treated with initial surgery will still require adjuvant RT (with or without chemotherapy) for adverse features on pathology and/or advanced nodal disease. These patients may be offered single-agent RT, concurrent chemoradiation, induction chemotherapy followed by RT, or sequential therapy (induction chemotherapy followed by chemoradiation). (See 'Concurrent chemoradiation' below.)
Sequential therapy is also reasonable approach in select patients with advanced primary or nodal disease. Sequential therapy can also be used to restore function prior to chemoradiation in patients with tumors resulting in significant trismus, impaired swallowing and tongue function, or airway obstruction requiring tracheostomy. Further details on the indications for sequential therapy are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Sequential therapy'.)
●Patients for whom surgery would result in poor postoperative functional outcomes – Such patients typically include those with significant soft palate or base of tongue tumor involvement where the surgical defect required to generate negative margins would significantly impair speech or swallowing. In such patients, excellent overall survival and swallowing results have been reported with definitive chemoradiation [6] and sequential therapy.
●Ineligible for concurrent chemoradiation or surgery - Patients who are identified during pretreatment assessment as poor candidates for concurrent chemoradiation or surgical therapy may be offered single-agent RT. For such patients, the primary intent of RT is curative, regardless of oropharyngeal function. (See 'Older adults' below.)
Concurrent chemoradiation
Rationale — Various clinical trials in patients with locally or regionally advanced squamous cell carcinoma of the head and neck have established the role of combinations of chemotherapy and RT as an organ-preservation technique. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Chemoradiation'.)
Data supporting the addition of chemotherapy to RT comes from the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC). In patients with head and neck cancer, this meta-analysis evaluated the efficacy of chemotherapy administered as neoadjuvant (induction), concurrent (concomitantly) with RT, or adjuvant therapy following definitive locoregional treatment (surgery and/or RT) [7-9]. Results of this meta-analysis for the entire study population are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)
When the MACH-NC was analyzed by tumor subsite, among the 5872 patients with oropharyngeal carcinoma (both HPV and non-HPV associated), at median follow-up of 5.6 years, the addition of concurrent chemotherapy to locoregional therapy decreased the risk of death (hazard ratio 0.88, 95% CI 0.82-0.93) [8]. This corresponded to an absolute improvement in five-year overall survival of 8 percent with concurrent chemotherapy [8]. There was also no clear survival benefit with adjuvant or induction chemotherapy, even when specific induction chemotherapy regimens were assessed. Similarly, in another randomized trial, among those with oropharyngeal carcinoma, the addition of induction chemotherapy to locoregional treatment did not improve survival [10]. (See 'Sequential therapy and induction chemotherapy' below.)
It is not clear if these data apply to HPV associated oropharyngeal cancer. Most of the studies included in the MACH-NC were conducted prior to the demographic and biologic shift in oropharyngeal cancer associated with HPV. However, treatment paradigms are similar for HPV associated and non-HPV associated oropharyngeal cancers. Additional studies conducted specifically for HPV associated oropharyngeal cancer are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Treatment approaches to deintensification'.)
Radiation schedule and technique — The standard RT approach for patients with advanced locoregional disease treated with concurrent chemoradiation is to use once-daily fractionation with intensity-modulated RT (IMRT) and image-guided RT (IGRT). (See "General principles of radiation therapy for head and neck cancer", section on 'Three-dimensional conformal RT'.)
We do not offer altered-fractionation RT schedules in patients with oropharyngeal carcinoma receiving concurrent chemoradiation, as no clear clinical benefit has been demonstrated over standard (once-daily) fractionation. Furthermore, twice-daily treatment schedules place greater time demands on the patient and the treatment facility, and they may create problems with compliance. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations".)
Altered-fractionation schedules, including hyperfractionation and accelerated RT, have been investigated to overcome accelerated repopulation and to safely escalate the dose. When RT is administered as a single modality (ie, without chemotherapy), hyperfractionation regimens improve both local control and overall survival compared with once-daily (conventional) fractionation. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Hyperfractionation'.)
Accelerated fractionation improves locoregional control, but its effect on overall survival is less than that with hyperfractionation [11] and similar to that of standard-fractionation in patients receiving concurrent chemoradiation. As an example, in one randomized trial (Radiation Therapy Oncology Group [RTOG] 0129) evaluating concurrent cisplatin plus either standard-fractionation RT or accelerated-fractionation RT, overall survival was similar between the two treatment schedules [12]. Further results of this trial are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Radiation therapy schedule' and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Accelerated fractionation RT'.)
Further studies are necessary to determine the role of intensity-modulated proton beam therapy in the treatment of oropharyngeal carcinoma. In one randomized trial of 147 patients with locoregionally advanced OPSCC, proton beam therapy was associated with improved work and productivity recovery trends compared with standard fractionated chemoradiation [13]. (See "Radiation therapy techniques in cancer treatment", section on 'Particle therapy'.)
Choice of chemosensitizer — Platinum-based regimens have shown superiority to non-platinum-based regimens when used concurrently with radiation for head and neck cancer, which is discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)
Dosing options include weekly cisplatin (40 mg/m2 weekly) and bolus cisplatin (100 mg/m2 every 21 days for two or three doses). These and other available regimens (including options for patients ineligible for cisplatin) for concurrent chemoradiation in patients with squamous cell carcinoma of the head and neck are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Concurrent chemotherapy'.)
In patients with HPV associated oropharyngeal cancer, cetuximab plus RT results in inferior survival compared with cisplatin plus RT. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Cetuximab versus cisplatin for definitive chemoradiation'.)
Management of the neck after RT — For patients with locoregionally advanced oropharyngeal carcinoma, management of residual abnormalities in the neck can be a particularly difficult issue. For patients with complete regression documented clinically and by structural (computed tomography [CT], magnetic resonance imaging [MRI]) or functional (positron emission tomography [PET]) imaging [14], observation is generally indicated, whereas salvage surgery is indicated in the absence of an adequate response (algorithm 2).
The management of the neck, including the extent of surgery, in patients treated with RT or chemoradiation is discussed separately. (See "Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma".)
Sequential therapy and induction chemotherapy
●Sequential therapy – Select patients with OPSCC may be evaluated for sequential therapy (ie, induction chemotherapy followed by chemoradiation), such as those with advanced primary disease or extensive lymph node involvement. In such patients, this approach may improve locoregional control and organ function, and prevent distant metastases. However, among patients with OPSCC, sequential therapy has not demonstrated an overall survival advantage compared with concurrent chemoradiation alone in randomized trials [15]. Further details on and the specific indications for sequential therapy are discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Sequential therapy'.)
●Induction chemotherapy followed by locoregional therapy – Induction chemotherapy followed by RT may be a reasonable option for those very select patients who are not ideal candidates for initial treatment with chemoradiation but may tolerate induction chemotherapy. However, randomized trials comparing these two treatment strategies are limited. Additionally, induction chemotherapy followed by RT is not superior to chemoradiation for oropharyngeal cancer and should not be regarded as a substitute. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Induction chemotherapy'.)
Although the MACH-NC study demonstrated no survival benefit with induction chemotherapy compared with locoregional therapy (ie, RT with or without surgery) alone, there was a small benefit for cisplatin and fluorouracil (FU) combinations in patients with oropharyngeal cancers [7-9]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)
Similarly, in one randomized clinical trial of 318 patients with oropharyngeal carcinoma, the addition of induction (neoadjuvant) chemotherapy with three cycles of cisplatin plus a five-day intravenous infusion of FU to definitive locoregional therapy alone (single-agent RT or surgery with RT) improved overall survival (median 5.1 versus 3.3 years) [10].
The general approach to sequential therapy and induction chemotherapy in patients with OPSCC is similar to that for other head and neck cancers and is discussed separately. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Available techniques'.)
Surgery
Patient selection (surgery) — For patients with locoregionally advanced OPSCC who are treated with surgery, options include TORS, TLM, or more extensive resection. Indications for nonsurgical approaches are discussed above. (See 'Patient selection (nonsurgical approaches)' above.)
Situations amenable to a surgical approach include the following:
●Smaller primary tumors (T1 to T2) with limited lymph node involvement where the primary tumor appears amenable to margin-negative resection and good postoperative functional outcomes – As an example, a good candidate for surgical resection is a patient with a T1 to T2, N1 (single involved node ≤3 cm) tumor involving the tonsils (without base of tongue extension) and without adverse features (eg, extranodal extension) on clinical exam or high-quality imaging. In such patients, it is anticipated that surgical resection would result in negative margins and good postoperative functional outcomes. However, either surgical or nonsurgical approaches may be appropriate, depending on the location of the tumor and patient preference. Multidisciplinary input is essential. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'T1-T2, single involved node (≤3 cm)'.)
In such patients, surgery may also reduce the overall radiation impact by reducing the field size, altering the RT dose, or eliminating the need for concurrent chemotherapy with RT. In the absence of these situations, surgery should not be performed unless it palliates a critical lesion in advance of definitive radiation or chemoradiation. Studies investigating these approaches are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Is there a role for treatment deintensification?'.)
●For patients with contraindications to RT – Patients with certain connective tissue disorders (eg, systemic lupus erythematosus and scleroderma) may not be candidates for RT due to risk of RT-induced fibrosis and may benefit from surgery instead. (See "Clinical manifestations, prevention, and treatment of radiation-induced fibrosis", section on 'Connective tissue diseases'.)
●For tumors with gross bony involvement – Most experts favor composite resection (mandibulectomy) over RT. While prospective randomized trials are lacking, gross mandibular invasion is difficult to cure with nonsurgical approaches and, in many cases, leads to osteoradionecrosis due to high doses of radiation to the mandible.
Surgical techniques for the primary tumor — Minimally invasive techniques to treat the primary tumor, such as TORS, are feasible and well tolerated in patients with resectable, locally advanced oropharyngeal cancer [5,16-18]. Another available option is TLM, which uses an endoscope to view the pharynx through the mouth and a laser to excise the tumor [19]. In most centers that perform minimally invasive surgery, TORS is used more frequently than TLM.
Minimally invasive surgical approaches allow adequate visualization and exposure of oropharyngeal primary tumors without the morbidity of mandibulotomy and lip split approaches. These approaches are most feasible for early tumor (T) stage tumors of the oropharynx, where function is more likely to be preserved. However, minimally invasive surgery become more challenging for tumors with advanced T stages where postoperative functional morbidity is more likely (eg, locoregionally advanced tumors with pterygoid involvement); in such tumors, nonsurgical therapy is preferred. (See "Treatment of early (stage I and II) head and neck cancer: The oropharynx", section on 'Surgical techniques'.)
Surgical management of the neck — The surgical management of the neck in patients with locoregionally advanced OPSCC is complex. The choice of treatment depends on the treatment modality used for the primary tumor (ie, neck dissection and/or RT), disease extent [20], and the response to therapy. The risk of residual occult disease must be also balanced against the complications of treatment.
For patients receiving surgical management of their primary oropharyngeal cancer, the initial surgical approach to the neck is determined by the extent of regional clinical lymph node involvement. There are no randomized studies directly comparing selective with comprehensive (ie, radical) neck dissection, and observational studies are limited [21-23]. Our approach is generally consistent with guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) [4,24].
●Clinically negative cervical nodes (N0) – For patients with clinically negative cervical nodes, regardless of T stage, we suggest selective neck dissection including at least levels II to IV (figure 2) rather than observation or more extensive surgical approaches. Although bilateral treatment is indicated for midline lesions (ie, base of tongue), ipsilateral neck treatment is sufficient for lateralized lesions (ie, tonsil).
●Early clinical nodal disease (single node ≤3 cm) – For patients with early clinical nodal disease (N1, metastasis in a single node ≤3 cm), we suggest selective neck dissection (including levels I to IV) rather than more extensive surgical approaches.
For patients with HPV associated tumors with a single node involving level II, neck dissection limited to level II through IV lymph nodes is a reasonable option due to low risk of disease involvement. This approach also avoids damage to the marginal mandibular branch of cranial nerve VII that could potentially occur with a level I lymph node dissection.
●Clinical N2 or N3 disease – For patients with oropharyngeal cancer and advanced nodal disease (N2 and N3), we suggest a comprehensive neck dissection rather than less extensive surgical approaches.
Indications for adjuvant radiation or chemoradiation — Patients treated with primary surgery for locoregionally advanced OPSCC will generally require adjuvant (postoperative) RT or adjuvant chemoradiation. An exception can be made for T1 N1 tumors with wide surgical margins; such patients may be observed, after multidisciplinary evaluation.
Postoperative chemoradiation should be used for positive resected margins and/or extranodal extension of lymph nodes. The management of tumors with these and other intermediate- or high-risk pathologic features are discussed separately. (See "Adjuvant radiation therapy or chemoradiation in the management of head and neck cancer".)
Treatment complications — Complications from concurrent chemoradiation and surgery are discussed separately.
●(See "Management of late complications of head and neck cancer and its treatment".)
●(See "Management and prevention of complications during initial treatment of head and neck cancer".)
SPECIAL POPULATIONS
Older adults — Single-agent radiation therapy (RT) is an option in many patients who are not candidates for concurrent chemoradiation because of age, poor performance status, or comorbidities. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Patient selection'.)
Concurrent chemoradiation is often avoided in many older patients with advanced oropharyngeal cancer, as well as in those with a poor performance status. In these patients, concurrent chemoradiation may result in toxicity that delays or prevents the completion of a course of definitive RT. Although older adults are underrepresented in clinical trials [25], overall survival benefit for concurrent chemoradiation is limited in those over the age of 70. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)
PROGNOSIS — The five-year relative survival rate for all stages of oropharyngeal carcinoma, regardless of human papillomavirus (HPV) status, is approximately 50 percent, based on data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review [26]. However, this study may inadequately reflect the HPV status of the tumors.
HPV associated oropharyngeal cancers have a better prognosis than non-HPV associated oropharyngeal cancers [27]. In clinical trials of patients with locoregionally advanced, HPV associated oropharyngeal cancer, long-term survival rates are approximately 80 percent or higher. Further details on the prognosis of HPV associated head and neck cancer are discussed separately. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer", section on 'Prognosis'.)
POSTTREATMENT REEVALUATION — After completion of therapy, posttreatment reevaluation is critical to ensure the absence of residual disease. For patients with advanced oropharyngeal carcinoma, the approach to posttreatment evaluation is based on the type of treatment received (surgery versus nonsurgical approaches) and is similar to that used for other sites of head and neck cancer. This topic is discussed separately. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck", section on 'Posttreatment reevaluation'.)
SURVEILLANCE — Regular posttreatment surveillance is an essential part of the care of patients with locoregionally advanced oropharyngeal cancer after potentially curative treatment. This topic is discussed separately. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck", section on 'Surveillance' and "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Surveillance'.)
In patients with non-HPV associated oropharyngeal cancer, continued follow-up is particularly necessary because of the risks of late complications, late recurrences, and second (subsequent) primary malignancies. (See "Second primary malignancies in patients with head and neck cancers".)
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".)
SUMMARY AND RECOMMENDATIONS
●Clinical presentation – Oropharyngeal squamous cell carcinomas (OPSCC) arises in the soft palate, tonsils, base of tongue, pharyngeal wall, or vallecula (figure 3). OPSCC is most commonly associated with human papillomavirus (HPV) infection, but can also be non-HPV associated (table 3). (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer", section on 'Clinical presentation'.)
●Staging – Separate American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging systems have been established for HPV associated (p16 positive) oropharyngeal carcinoma (table 1A-B) and for non-HPV associated (p16 negative) oropharyngeal cancer (table 2A-B). (See "Overview of the diagnosis and staging of head and neck cancer".)
●Definition – Locoregionally advanced (generally, stage III and IV) OPSCC are typically larger primary tumors (T3 or T4) with or without lymph node involvement (figure 2); or smaller primary tumors (T1 or greater) with lymph node involvement, but without distant metastases. (See 'Definition' above.)
●Management – For patients with locoregionally advanced OPSCC (regardless of HPV status), treatment options include both nonsurgical approaches (RT with or without chemotherapy) and primary surgery (followed by either adjuvant RT or adjuvant chemoradiation, as indicated). In general, nonsurgical options are more frequently used, as primary surgery is often limited to the subset of patients where postoperative functional morbidity is anticipated to be minimal. (See 'Management' above.)
●Selecting a nonsurgical approach – Situations in which a nonsurgical approaches may be favored include (see 'Patient selection (nonsurgical approaches)' above):
•Unresectable disease.
•Patients in whom surgical resection would result in poor functional outcomes.
•Patients ineligible for concurrent chemoradiation or surgery due to age or comorbidities. These patients are offered single-agent RT. (See 'Older adults' above.)
●Choice of chemosensitizer – For most patients treated with concurrent chemoradiation, cisplatin is used as the chemosensitizer, which is discussed separately. (See 'Choice of chemosensitizer' above and "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Concurrent chemotherapy'.)
●Situations amenable to a surgical approach – Situations in which a surgical approach is an option or may be favored include (see 'Patient selection (surgery)' above):
•Smaller primary tumor (T1 to T2) with limited lymph node involvement where the primary tumor appear amenable to margin-negative resection and good functional outcomes. For such patients, either surgical or nonsurgical approaches may be appropriate, depending on the location of the tumor and patient preference. Multidisciplinary input is essential. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'T1-T2, single involved node (≤3 cm)'.)
•Patients with connective tissue disorders that are contraindications to RT.
•Tumors with gross bony involvement at risk for osteoradionecrosis with RT.
●Surgical techniques for the primary tumor – Minimally invasive techniques, such as transoral robotic surgery (TORS) and transoral laser microsurgery (TLM), are feasible and well tolerated in select patients with resectable, locally advanced OPSCC. (See 'Surgical techniques for the primary tumor' above.)
•For patients treated with surgery, minimally invasive surgery is typically preferred over more extensive surgical techniques. (See "Treatment of early (stage I and II) head and neck cancer: The oropharynx", section on 'Surgical techniques' and "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Surgical technique'.)
●Management of the neck – Management of the neck is complex and depends on the treatment modality used for the primary tumor, the disease extent, and response to therapy.
•Primary surgery – For patients whose primary tumors are treated with surgery, the surgical approach to the neck is determined by the extent of regional lymph node involvement as follows (see 'Surgical management of the neck' above):
-Clinically negative cervical nodes (N0) – We suggest selective neck dissection, including at least levels II to IV (figure 2), rather than observation or more extensive surgical approaches (Grade 2C).
-Early clinical nodal disease (N1, single node ≤3 cm) – We suggest selective neck dissection, including levels I to IV, rather than more extensive surgical approaches (Grade 2C).
For patients with HPV associated tumors with a single node involving level II, neck dissection limited to level II through IV lymph nodes is a reasonable option due to low risk of disease involvement. This approach also avoids damage to the marginal mandibular branch of cranial nerve VII that could potentially occur with a level I lymph node dissection.
-Clinical N2 or N3 disease – We suggest comprehensive neck dissection rather than less extensive surgical approaches (Grade 2C).
•Definitive RT – For patients whose primary tumors are treated with definitive RT or chemoradiation, the management of the neck is discussed separately. (See 'Management of the neck after RT' above and "Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma".)
●Management of HPV associated OPSCC – Further details on selecting therapy for locoregionally advanced HPV associated OPSCC are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Carol R Bradford, MD, FACS, who contributed to an earlier version of this topic review.
