Soft Palate

The soft palate incompletely separates the nasopharynx and oral cavity from the oropharynx. It is built by the palatopharyngeal arch and the uvula containing the levator and tensor muscle of the palate, the uvular muscle, and laterally the palatopharyngeal and constrictor muscles. Small salivary glands exist within the soft palate tissue. The blood supply is based on the palatine arteries accompanied by palatine sensory nerves.

Tonsillar Fossae

The tonsillar region contains the lymphoid tissue of the palatine tonsil, located on the lateral pharyngeal wall. The vascular supply of the palatine tonsils is covered by posterior branches of the lingual artery, the ascending pharyngeal artery, branches of the facial artery, and palatine branches of the internal maxillary artery. The tonsils are embedded in the anterior and posterior pillar, formed by the palatoglossus and the palatopharyngeal muscle, respectively.

Base of Tongue

The base of tongue reaches from the circumvallate papilla to the vallecula and to the glossopalatine sulci laterally. The tongue base is rich in lymphatics and contains part of Waldeyer’s ring. The blood supply is covered by the lingual arteries. Innervation of the tongue musculature is provided by the hypoglossal nerve (Fig. 100-2).

Figure 100-2. Cross-sectional anatomy of the oropharynx.

Oropharyngeal Wall

The posterior pharyngeal wall of the oropharynx reaches from the region of the soft palate to the epiglottis and borders the tonsillar fossae and the lateral aspect of the piriform sinuses laterally. The wall is composed of superior constrictor muscle and the buccopharyngeal and pharyngobasilar fascia covered by the pharyngeal mucosa (Fig. 100-3).

Figure 100-3. Deep anatomy of the oropharyngeal muscles, nerves, and blood vessels.

Lymphatics

The lymphatic pattern of the oropharynx is complex, and lymphatic spread from malignant lesions depends on size and location of the primary malignancy. Its understanding is of high importance for the outcome of surgical and/or radiotherapy treatment of oropharyngeal lesions. A number of previous studies have defined the routes of lymphatic spread in the head and neck.^2–4 The clinical neck levels are defined by levels I to VI with subdivisions A and B for levels I, II, and V (Fig. 100-4).⁵

Figure 100-4. Lymph node chains of the neck that may be involved with cervical metastatic spread from oropharyngeal tumors. A, Superficial cervical and facial nodes. B, Deep cervical and intraparotid lymph nodes.

Rights were not granted to include this figure in electronic media. Please refer to the printed book.

Oropharyngeal carcinoma is predisposed to drain to levels II, III, and IV with possible further spread to other regions in extensive disease.⁶ However, primary drainage is to the jugulodigastric nodes in the upper deep jugular chain (level II) and to the retropharyngeal and parapharyngeal nodes in the retropharyngeal and parapharyngeal space, respectively. Other metastatic spread may involve midcervical (level III) and lower cervical nodes (level IV). Skip metastases to other clinical levels are extremely rare. Shah described in a retrospective study of 1119 radical neck dissection specimens that tumors of the oropharynx characteristically metastasized to lymph node levels II to IV. There was no positive node involvement of level V when levels II to IV were negative.⁷

Attention should be spent on the location of the primary malignancy near the midline. Tumors of the base of tongue, the soft palate, and the posterior pharyngeal wall have a higher incidence of bilateral lymphadenopathy. These considerations should influence therapeutic planning to optimize therapy and minimize patient morbidity (Figs. 100-5 and 100-6, Table 100-1).

Figure 100-5. Lymphatics of the base of the tongue, with jugulodigastric node involved first.

Rights were not granted to include this figure in electronic media. Please refer to the printed book.

Figure 100-6. Bilateral base of tongue lymphatic drainage.

Rights were not granted to include this figure in electronic media. Please refer to the printed book.

Epithelial Precursor Lesions

In general, precursor lesions of the oropharynx clinically present as white patches (leukoplakia) (Fig. 100-7) or red patches (erythroplakia). Some lesions appear as mixed variants with white and red components. Most white lesions do not show dysplastic cells and relate to hyperplasia. However, erythroplakia or mixed lesions frequently display dysplasia. Whereas leukoplakia rarely undergoes malignant transformation and may even regress after elimination of underlying etiologic factors, erythroplakia can often lead to malignancy.

Figure 100-7. Leukoplakia of the tongue.

Hyperplasia describes increased cell counts in the spinous layer (acanthosis) or in the basal/parabasal layers. The cells are free of atypia and tissue architecture is regular.

In case of changes in architecture and in the presence of atypia in cells, we speak of dysplasia. Dysplasia is considered a range and it is somewhat challenging to divide the dysplastic spectrum into mild, moderate, and severe.

Mild dysplasia is described as mild cell atypia with architectural changes limited to the lower third of the epithelium.

Moderate dysplasia shows architectural changes up to the middle third of the epithelium and cytologic atypia.

Severe dysplasia begins with architectural changes over two thirds of the epithelium and atypic cells. Again, there is no definite division of dysplastic variants and, depending on the degree of cell atypia, upgrading of dysplasia categories might have to be considered.

Carcinoma in situ is described as malignant transformation without invasion, which is difficult to distinguish morphologically. WHO experts recommend that CIS be diagnosed when full-thickness architectural abnormality and severe cytologic atypia is found.⁹

Squamous Cell Carcinoma

SCC is defined as an invasive epithelial neoplasm with varying degrees of squamous differentiation and a propensity to early and extensive lymph node metastases, occurring predominantly in alcohol- and tobacco-using adults in the fifth and sixth decades of life.¹⁰ The clinical appearance varies and presents as exophytic, flat, ulcerated, verrucoid, or papillary in growth (Fig. 100-8). Independent from the gross appearance, histopathologic patterns of invasion demonstrate multiple variations as well. SCC can vary from keratinizing to nonkeratinizing and well differentiated to poorly differentiated. Severe dysplasia and CIS are common elements found in association with invasive SCC. Invasive carcinoma eliminates the regular architecture and can include lympho-vascular space invasion, neurotropism, and infiltration of other tissue components such as muscle or cartilage, demonstrating aggressive behavior of the tumor.

Figure 100-8. Squamous cell carcinoma of the left tonsil (arrows).

Most invasive SCC can easily be identified by experienced pathologists. However, early clinical stages might significantly complicate the diagnosis of invasive patterns. Inflammation can make detailed analysis of the deep epithelial layers and the lamina propria difficult. Presence of cytologic atypia and mitotic features can lead to the correct diagnosis, although they cannot be found in all cases of early SCC pathology. Borderline cases without unambiguous evidence of invasion might still be called early invasive carcinoma after communication between clinician and pathologist.

Malignancy grading can be a prognostic marker, although different grading systems have been proposed with diverse impact on prognosis. Broders suggested a four-tiered grading system for carcinoma of the lip in 1929.¹¹ His grading system allows assessment of tumor differentiation with some predictability of prognosis because poorly differentiated tumors are more likely to recur.^12,13 However, the grading system has also been shown to lack consistent prediction of prognosis using multivariate analyses.^14,15 A subsequent multivariate analysis on 77 patients with oropharyngeal cancer unveiled only the invasive pattern of the tumor to be an independent predictor for patients’ survival.¹⁶ Anneroth and colleagues¹⁷ proposed that grading should include six morphologic features: degree of keratinization, nuclear polymorphism, number of mitoses, pattern of invasion, stage of invasion, and lymphoplasmacytic infiltration. Bryne and colleagues¹⁸ revised this grading method, applying Anneroth’s criteria to the most anaplastic fields in the areas of highest infiltration. This invasive cell grading was demonstrated to be a highly significant predictor for oral SCC patients’ outcome and survival.^18–20 Table 100-3 summarizes the invasive cell grading system (ICG) by Bryne and colleagues.

The present WHO grading system has been recommended for histopathologic typing of oropharyngeal cancers by the American Joint Committee on Cancer (AJCC).²¹ This grading system is based on Broders’ system and includes three grades, which are described in Table 100-4.

Table 100-4 World Health Organization Grading System for Oral Squamous Cell Carcinoma

From Pindborg JJ, Reichert PA, Smith CJ, et al, eds. Histological Typing of Cancer and Precancer of the Oral Mucosa. 2nd ed. Berlin: Springer-Verlag; 1997:11. By permission of the publisher.

Lymphoepithelial Carcinoma

The lymphoepithelial carcinoma is defined as a poorly differentiated SCC or undifferentiated carcinoma, accompanied by a prominent reactive lymphoplasmacytic infiltration. The lymphoepithelial carcinoma is rare and diagnosed in 0.8% to 2% of all oral and oropharyngeal malignancies.²² More than 90% of all lymphoepithelial carcinoma in the oral and oropharyngeal region is found in the tonsils and the base of tongue. Some are found in the buccal mucosa and the palate.

The histopathologic pattern is described as invasive, comprising syncytial sheets and clusters of carcinoma cells with prominent nucleoli, ill-defined cell borders, and often intact surface. The tumor sites are accompanied by rich lymphoplasmacytic infiltrate. These tumors are radiosensitive and local control can be achieved in a high percentage of cases.²³

Salivary Gland Tumors

Among malignant salivary gland tumors, 9% to 23% are found in the oral cavity and oropharynx.^24–26 Nearly half of the salivary gland tumors in the oral cavity and oropharynx are malignant.²⁴ However, most neoplasms of minor salivary glands arise in the oral cavity. The most common oropharyngeal sites are the (soft) palate, the tonsillar fossa, and base of tongue. Oropharyngeal salivary gland tumors are rare with only 1.1% to 3.3% of all minor salivary gland tumors.^24,25,27 All malignant salivary gland tumors that can possibly arise in the oropharynx are listed in Table 100-2. Among those, adenoid cystic carcinoma and the mucoepidermoid carcinoma are most frequent.

The adenoid cystic carcinoma is relatively common in minor salivary glands. A large series describes 42.5% of this lesion to be found in minor glands and 20.5% of minor salivary gland adenoid cystic carcinoma in the oral/oropharyngeal space.²⁸ They usually present as slow-growing masses, sometimes with ulceration of the palate. Symptoms like pain, signaling nerve invasion, suggest progressive disease. The histopathologic pattern is cylindromatous or cribriform, although some can show tubular areas or appear solid.²⁹ Cribriform lesions have a more favorable prognosis than solid tumors. The spread of adenoidcystic lesions is commonly hematogenous, typically in the lung and bones, and lymph node involvement is rather rare. Therefore neck dissection is generally reserved for patients with palpable disease.³⁰ In case of radiation therapy for these rather moderately radiosensitive tumors, neutron beam radiation is recommended.³¹ Prognosis is negatively influenced by minor salivary gland as origin, tumor size greater than 4 cm, osseous invasion, advanced stage, and local recurrence.^32,33

Mucoepidermoid carcinoma is the most common salivary gland malignancy and accounts for 9.5% to 23% of all minor salivary gland tumors.^25,34,35 Half of the often asymptomatic cases arise in the palate, whereas the base of tongue and other oropharyngeal locations are rare.³⁶ They are commonly well differentiated and appear as a bluish swelling. Some show granulation or a papillary surface. Oropharyngeal tumors can cause symptoms of dysphagia. Histopathologically, a mixture of epidermal epithelium and mucous membrane-producing cells is found. Treatment usually includes wide surgical excision, and neck dissection appears to be beneficial in patients with suspected or clinically obvious metastases. Olsen and colleagues reported on a series of oropharyngeal mucoepidermoid carcinoma at Mayo Clinic. Based on a follow-up of at least 10 years, recurrence rate was significantly reduced after wide local excision, including bone if necessary compared with simple excision with closer margins. Of the patients in the series, 24% presented with positive lymph nodes.³⁷ Patients treated with primary radiation or postoperative radiation did not profit in terms of local control or survival in this evaluation; however, numbers might be too small to draw final conclusions and radiotherapy might be beneficial in case of adverse effects in those patients.

Soft Tissue Tumors

Kaposi’s sarcoma is a locally aggressive growing neoplasm, which might present as cutaneous but also as mucosal lesion, showing multiple patches and nodules (Fig. 100-9). It can also affect lymph nodes and visceral organs. It rarely metastasizes and is a member of intermediate-type vascular tumors. It is associated with human herpes virus 8 (HHV 8) infections. Kaposi’s sarcoma occurs as an indolent variant in elderly men in the Mediterranean and Eastern Europe, as endemic disease in equatorial Africa, and in immunosuppressed patients after organ transplantation or in case of human immunodeficiency virus (HIV) infection.³⁸

Figure 100-9. Kaposi’s sarcoma of the palate.

Oral Kaposi’s sarcoma is found predominantly on the palate, the gingiva, and the tongue. It clinically presents as reddish blue or brown nodules or plaques with possible ulceration. The AIDS-related form of Kaposi’s sarcoma is the most aggressive form. There are three histopathologic stages of Kaposi’s sarcoma: the patch stage in early lesions, the plaque stage, and the nodular stage. Stages can be considered a spectrum and they blend into another. Early lesions are uncharacteristic, showing vascular proliferation, collagen fibers, hyaline globules, endothelial cell lining, and cells with some atypia and infiltration of inflammatory cells as they grow.

Patients might be treated with surgery, radiation, and chemotherapy, depending on the epidemiology of the disease. The incidence and course of the disease has improved with antiretroviral therapy in HIV-infected patients.³⁸

Hematolymphoid Tumors

On the basis of the complex and widespread lymphatic tissue in the oropharynx, lymphoid malignancies often occur in this area. Non-Hodgkin’s lymphomas (NHLs) are found in the palatine tonsils, palate, base of tongue, and other oropharyngeal sites. Etiologic factors are yet unknown in most patients, although some lymphoma patients might suffer from an immunodeficiency. Clinical symptoms can be fullness of the throat, dysphagia, snoring, and pain. Systemic symptoms are rare.³⁹ The lesions present as exophytic mass, submucosal swelling, and sometimes ulcerations (Figs. 100-10 and 100-11).

Figure 100-10. Non-Hodgkin’s lymphoma of the palate with submucosal swelling and ulceration.

Figure 100-11. Lymphoma of the tonsil (arrow).

Most NHLs in the oropharynx are B-cell lymphomas, with diffuse large B-cell lymphoma being the predominant type. Histopathologically the stroma is densely infiltrated with lymphoma cells, which vary depending on the histologic type. Treatment is based on radiotherapy and/or chemotherapy depending on the histologic type and stage. Studies have demonstrated a benefit for adjuvant chemotherapy along with radiation compared with radiation treatment only.^40,41 The 5-year survival rate for localized disease has been reported from 50% to more than 80%.^41–45

Mucosal Malignant Melanoma

Although malignant melanoma (MM) most commonly manifests as skin lesions, it may also arise from melanocytes in the mucosa, but only 1.3% of all melanomas are mucosal melanomas (Figs. 100-12 and 100-13). Of those, 55.4% are mucosal MMs of the head and neck.⁴⁶ They are characterized as malignant transformed melanocytes at the epithelial–connective tissue interface with migration into the epithelium and the connective tissue, respectively. Oropharyngeal mucosal melanoma is exceedingly rare, with more mucosal MM of the head and neck occurring in the oral cavity (50%).^46,47

Figure 100-12. Malignant melanoma of the retromolar trigone.

Figure 100-13. Malignant melanoma of the left tonsillar fossa.

No known etiologic factors exist for mucosal MM of the head and neck. Clinically they can present as black, gray, or reddish, and they are rarely amelanotic. They typically consist of widespread, multiple, pigmented lesions with or without nodules. Ulcerations and bone infiltration are common and oral bleeding, dysphagia, and sensations of pain can be symptoms before diagnosis. Mucosal MM is usually diagnosed in an advanced stage with most tumors showing invasive character. However, 20% are in situ lesions.⁴⁷ Aggressive surgical resection is still the primary treatment of choice, although many adjuvant modalities including different chemotherapy regimens and radiotherapy have been applied. Despite surgically achieved possible local control, 5-year survival of pharyngeal melanoma is only 13%.^46,48,49 Developments for improved treatment options are limited because mucosal MM is a rare disease lacking clinical treatment trials. By early detection, melanoma patients have the best chance for cure and physician’s threshold for biopsy of a suspected lesion should be low.

Etiology

Predominant and synergistic acting risk factors for SCC of the oropharynx are tobacco and alcohol consumption.⁵⁰ These factors account for about 75% of oral and oropharyngeal carcinoma in Western countries.^50,51 For the highest consumption levels, relative risks from 70 to 100 have been reported compared with lowest consumption levels. A super-multiplicative effect in case of contact with tobacco and alcohol substances has been shown for oral and oropharyngeal cancers in case-control studies.⁵²

Tobacco chewing is a common habit, particularly in India, parts of Southeast Asia, the Middle East, China, and Taiwan. Tobacco is often consumed in betel quids containing areca nut, which has been classified as human carcinogen by the IARC in 2003. Smokeless tobacco is a major risk factor for oropharyngeal cancer in these parts of the world.⁵³ In India about 50% of oropharyngeal cancers in male and 90% in female are caused by chewing.⁵⁴

Human papillomavirus (HPV) infection is another well-established cancer risk factor. Genotypes HPV 16 and 18, known causes for uterine cervix and skin cancer, are found in 50% of tonsillar and oropharyngeal SCC, and studies suggest that up to 40% of oropharyngeal cancer cases may be due to HPV infection.⁵⁵ The incidence of HPV-associated oropharyngeal primaries is rising according to recent reports—up to 70% of all presenting cases in some series. The cohort of patients harboring this form of the disease is younger by approximately 10 years and has a distinctly favorable prognosis. Epidemiologic studies propose that having multiple sexual partners is significantly associated with HPV-related tumors.¹

In addition to exogenic risk factors, multiple endogenic risks have been identified and associated with head and neck cancer.⁵⁶ DNA repair, differences in mutagen sensitivity, and alteration of genes such as epidermal growth factor receptor (EGFR) have shown their impact on head and neck cancer and influenced modern therapy and prevention strategies.

Clinical Presentation, Patterns of Spread

Patients with SCC of the oropharynx often present at advanced stages III and IV. Despite psychologic and social factors, late symptoms might cause prolonged und undiscovered tumor growth. First symptoms may be dysphagia, pain, feel of throat mass, oral bleeding, otalgia (involvement of cranial nerves IX and X), or presentation of a neck mass. Oropharyngeal regions can vary in clinical presentation and pattern of spread, causing different considerations for diagnostics and treatment.

Cancers of the soft palate present almost always on the anterior oropharyngeal portion. They are well detectable and can in most cases be biopsied in the office. Primary lymphatics involved are commonly level II nodes, with other levels involved depending on the clinical stage. Whereas midline and paramedian lesions have a tendency for bilateral lymphatic spread, this becomes more unlikely the more lateral the tumor growth is located.

The most frequent location for oropharyngeal tumors is the tonsillar fossa, with the palatine tonsil and the anterior tonsillar pillar. They commonly present as foreign body, dysphagia, otalgia, or impeded jaw mobility caused by infiltration of the periosteum or bone of the mandible or the pterygoid muscles in extended cases. Physical examination can show exophytic or ulcerated lesions, dysplasia, and/or inflammation reaction. Extension into the base of tongue inferiorly and the soft palate superiorly is common, with 55% and 60% in a study by Perez and colleagues, respectively.⁵⁷ Lymphatic drainage is directed primarily to level II nodes but can involve level III parapharyngeal and retropharyngeal nodes level I, IV, and V, depending on stage of presentation.^58–60 Lindberg described nodal metastasis for cancer of the tonsil in 76% of cases compared with 45% in patients with cancer of the tonsillar pillar, with most common node involvement in level II for both locations. Contralateral nodal disease was found in 11% of patients with cancer of the tonsil and 5% with primary malignancy of the pillar.⁶¹ However, in these studies no mention is given of proximity to the midline, which is the most frequent reason a lateralized tumor epicenter in the oropharynx would present with “contralateral” neck metastasis. Differences might be based on higher-staged groups with tonsillar lesions, and likelihood of contralateral lymphatic spread is less than 5% for T1 and T2 cancers.

Cancer of the base of tongue is particularly difficult to detect and often becomes clinically evident in an advanced stage. This is due to relatively late clinical symptoms because the base of tongue is nearly without pain fibers. Moreover, the assessment of the base of tongue can be more difficult during physical examination due to prominent lingual tonsils or submucosal location, and deep basal areas might not completely present even using operative endoscopy. As in the palatine tonsil, occult carcinoma with clinically prominent metastatic disease, typically in neck level II, is often found in the base of tongue and is often the presenting feature of this disease. As with neck metastases primarily clerived from tonsils, some of these neck masses can be misdiagnosed as branchial cleft cysts or, on biopsy, as branchiogenic carcinomas.⁶² To rule out such findings, meticulous microendoscopic examination (see Fig. 100-12) and biopsy of suspected lesions are mandatory. Base of tongue cancer has a higher frequency of bilateral metastases (up to 20%), which is mainly due to proximity to the midline but enhanced by a rich lymphatic drainage of the base of tongue and tendency to late clinical presentation with upstaging. Ipsilateral node involvement can be detected in more than 70% of cases.⁶³

Prolonged diagnosis is also common in oropharyngeal wall tumors. Symptoms can be pain, dysphagia, and bleeding. Infiltration of the prevertebral fascia posteriorly and deep cervical structures and vessels laterally negatively affect therapeutic options and prognosis. Lymphatic spread is found in about 25% of T1 and in 75% or more of T4 cancers. Most pharyngeal wall tumors come close or past the midline with frequent bilateral lymphatic spread. Microscopic parapharyngeal and retropharyngeal lymphatic spread has to be considered even in small lesions without palpable cervical nodes.

Anamnesis

A thorough anamnesis is part of any comprehensive evaluation of head and neck cancer patients. Symptoms at first presentation of oropharyngeal cancer patients are commonly dysphagia and/or odynophagia, oral bleeding, otalgia, or changes in speech. In addition to the history of risk factors such as alcohol and tobacco consumption, xenobiotic exposure at working places and in the environment should be evaluated. Dietary and social habits are also worthwhile to evaluate. Knowing about possible risk factors for head and neck cancer in individual patients enables for future elimination and enlarges the chances for prevention of recurrent disease. Also, better results and improved treatment tolerance are obtained for patients who quit smoking.⁶⁴ Other factors such as social aspects, family support, and general health status have great impacts on treatment and outcome and should therefore be consequently evaluated.

Physical Examination

Physical examination is one of the initial keys for cancer diagnosis, selection of further diagnostics, and treatment plan. In case of suspicion for oropharyngeal cancer, patients should carefully be investigated with focus on the tongue (appearance and movement), tonsillar fossae, retromolar trigone, soft palate (appearance and mobility), base of tongue, vallecula, and pharyngeal walls. Inspection should include a close endoscopy (flexible or rigid) and palpation, especially of the tongue base and sensate testing. Examination can unveil local tumor extension and nerve infiltration. Video endoscopy and documentation of findings are helpful tools for teaching reasons and future comparisons.

All cancer patients need to undergo a complete head and neck investigation to exclude secondary cancers. Bimanual palpation of the neck is mandatory in order to assess lymph node status and possible regional tumor spread.

Imaging

For most head and neck malignancies, imaging is an important and recommended tool for diagnostics and clinical staging. Oropharyngeal malignancies, especially with their close anatomic relationship to important soft tissue and bony structures, require further imaging studies for precise evaluation and treatment plans.

Gray-scale and Doppler ultrasonography of the neck have proven to be valuable methods to evaluate lymphadenopathy of the neck. Using ultrasound for cervical assessment has advantages. It is a relatively inexpensive procedure with real-time imaging and can be frequently performed without radiation exposure. However, there is limitation to ultrasonography in patients with head and neck malignancies. Retropharyngeal nodes and deep structures are not accessible using ultrasound. Furthermore, ultrasound has deficits describing extracapsular spread and infiltration of soft tissue and bone. Moreover, the oropharyngeal primary usually cannot be detected using ultrasonography.⁶⁵

Most oropharyngeal malignancies today are evaluated using computed tomography (CT) or magnetic resonance imaging (MRI). Sometimes the imaging technique preferred simply depends on its availability. Each has its advantages and disadvantages. Some oropharyngeal malignancies involve bony structures such as the maxilla, mandible, cervical spine, and skull base, and a CT scan might be helpful in interpretation of bone infiltration, although modern MRI precisely demonstrates infiltration of the periosseous membrane and allows for exact interpretation of bone involvement. In some cases panoramic x-ray views of the mandible can support identification of mandibular infiltration. Especially in deep invasive malignancies, MRI is helpful, although it can lead to false-negative results regarding superficial lesions. Although magnetic resonance scanning is generally the most recommended imaging method for the evaluation of the oropharynx and the neck, both CT and MRI have been used in such determinations.⁶⁶ Positron emission tomography (PET)/CT plays an increasing role for the management of head and neck SCC. It can unveil unknown primary tumor sites and synchronous primary tumors, regional lymph node metastases, and distant metastases. It plays a lesser role for T-staging of a known primary based on decreased anatomic definition compared with MRI and contrast-enhanced CT.⁶⁷ Its reliability may be limited by previous surgical or radiation therapy. Recent studies suggest that PET/CT is more accurate 2 to 3 months after completion of radiation therapy.^68–70 Whereas a negative PET/CT is found to be highly reliable, positive results must be correlated with findings in physical examination and cross-sectional imaging modalities because nonspecific inflammation may cause false-positive results.⁷¹

In addition to evaluation of locoregional tumor spread, imaging systems are used to screen for distant metastatic spread in organs such as the lung, liver, skeletal system, and brain. On the basis of the primary malignancy and the accompanying likelihood of distant metastases, regular chest radiographs and ultrasonography of the abdomen might be sufficient staging methods. In many cases, CT scanning of the lung and CT and/or MRI for the abdomen are recommended. In recent years, FDG PET/CT showed growing importance for the detection of distant metastatic spread.⁷¹

Endoscopy, Biopsy, and Frozen Section

To further diagnose oropharyngeal lesions, a biopsy and histopathologic examination must be performed. Biopsies of oropharyngeal tumors might be taken under local anesthesia. Lymphadenopathy without perceptible primary lesion can be evaluated using fine-needle aspiration (FNA). Best diagnostic results are found for FNA using ultrasound of the neck.⁷²

Some oropharyngeal lesions are not sufficiently accessible in the office setting and may require general anesthesia to biopsy an adequate-sized specimen. Occasionally small oropharyngeal malignancies can be difficult to detect in physical examination, as well as in imaging systems, and demand further diagnostics (e.g., using endoscopes with or without microscopic assistance) (Fig. 100-14). Microscopic evaluation is a sensitive procedure for the identification of unknown primary lesions, which can often be detected in the base of tongue or tonsillar fossa, respectively. The panendoscopy in general anesthesia is an important tool not only to detect and biopsy such lesions and to define tumor extension but also to rule out any secondary malignancy, which can be found in head and neck cancer patients and includes endoscopy of the bronchi and esophagus.

Figure 100-14. Microendoscopic setting.

Frozen sections as confirmation of a suspected malignancy and as criteria for tumor-free margins have been critically evaluated in the past.⁷³ The reliability of frozen sections depends on the experience and technique of the pathologist and requires close interdisciplinary communication. The accuracy of frozen sections is close to the final diagnosis (>90%).⁷⁴ Considering the possibility of false-positive results, depending on the examiner’s expertise, frozen sections cannot be generally recommended as a basis for final treatment, however. The final treatment should be based on standard histopathology.

Staging

The Union Internationale Contre Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in its Cancer Staging Manual (sixth edition) have defined the current staging system for oropharyngeal cancer.^75,76 Both classifications correspond exactly. Tables 100-5 and 100-6 present an overview of the present oropharyngeal staging system.

Table 100-5 Definition of the Tumor Node Metastasis Staging System

Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago. The original source for this material is the AJCC Cancer Staging Manual, 6th ed. (2002) published by Springer-Verlag New York, www.springer-ny.com.

Experts have debated and evaluated the clinical use of the staging system.⁷⁷ The fifth edition of the tumor node metastasis (TNM) classification divided stage IV tumors into three subcategories (IVA, IVB, and IVC), which already caused relevant changes to the fourth edition.⁷⁸ The sixth edition of the TNM classification introduced a subdivision of advanced tumors of group T4 into T4a (lower risk) and T4b (higher risk), which describes the risk of uncontrolled disease in patients with tumor extension beyond the site of origin. T4a disease describes tumors with reasonable opportunity for disease control on the basis of the resectability of structures involved such as larynx, deep/extrinsic muscles of the tongue, medial pterygoid, mandible, and hard palate. T4b describes tumors with certainty of poor outcome showing involvement of the lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base, or carotid artery. O’Sullivan and Shah⁷⁹ suggested invasion of the prevertebral fascia to be classified as high risk and therefore included into subgroup T4b. T4a and T4b in combination with categories for N (regional lymph node disease) and M (distant metastasis) assist the classification of the advanced tumor stage IV into the subgroups with advanced lower-risk stage IVA (potentially curable), advanced higher-risk IVB (of dubious curability), and stage IVC with distant metastatic disease (undoubtedly incurable). Despite some suggested additions, the sixth edition of TNM classification offers valuable assistance in clinical management and research. Changes in the staging system over the past decades and improvements of staging tools such as modern imaging systems must be taken into consideration when former clinical studies about outcome and prognosis are evaluated.

Despite the importance of therapeutic management, outcome, and prognosis, clinical staging remains strongly dependent on the examiner’s skills, the imaging system and its quality, and the excellence of surgical and pathologic assessment.

Oropharyngeal cancer is usually amenable to direct or endoscopic visualization and palpation, which in combination with imaging assessment enables a thorough clinical evaluation. Reasons for misjudgment remain. The examiner’s evaluation does not unveil microscopic and deep infiltration. Using MRI and CT scanning for further information results might be limited when examining superficial smaller lesions.⁶² Additionally, poor demarcation and accompanying inflammatory tissue reaction may affect interpretation of the images. Tumor size can be overestimated or underestimated by these factors and misjudged, and it can strongly influence therapeutic planning. Not only clinical but also postoperative staging might be affected (e.g., by shrinkage of the specimen and lack of clinical and surgical information). Moreover, large tumor extension might lead to difficulties about classification of the site of origin (e.g., whether a lesion derived from the oropharynx, hypopharynx, or supraglottic region). Because those tumor extensions commonly accompany high staging and comparably worse prognosis, there is less influence concerning management strategies but concerning scientific studies and statistical evaluation. Nevertheless, correspondence between the clinician and the pathologist is the key for best postoperative staging.

Therapeutic Management and Outcome

The main criterion for a successful treatment is locoregional control of the primary tumor. The choice of treatment modality depends on the location of the primary and the ability to control the primary and the regional node involvement. Figure 100-15 presents an informing algorithm for oropharyngeal cancer treatment. With improvements in locoregional control, distant metastases are a growing issue in the treatment of oropharyngeal cancers. To achieve this goal, surgery, radiotherapy, and chemotherapy can be administered alone or in combinations. In case of an early tumor stage, surgery and radiation therapy can be used for primary treatment. In later stages of oropharyngeal cancer, combinations of surgery, radiation therapy, and chemotherapy are recommended in most cases. The impact of additional therapies such as immunotherapy/biotherapy (e.g., epidermal growth factor receptor [EGFR] inhibitor) is currently investigated and their significance has yet to be evaluated. The decision-making process for treatment modality should include information from the latest review of the Cochrane Collaboration on the treatment on oral and oropharyngeal cancer. Only one study by Robertson (1998) compared surgery plus adjuvant radiotherapy and radiotherapy alone, fitting their criteria and therefore being included. The trial was prematurely stopped because of the unacceptably high number of deaths in the radiotherapy arm.^80,81 However, in addition to outcome, post-therapeutic function associated with the patient’s quality of life must be considered in the decision about treatment.

Figure 100-15. Management algorithm for squamous cell carcinoma of the oropharynx.

With the use of modern free tissue transfer techniques, patients’ quality of life and functions like speech and swallowing have considerably improved after surgery with ablative defects.⁸² Patients should be thoroughly informed about possible treatment options to be included in the decision-making process. Complications and long-term effects possibly arising from surgical interventions or toxicity of chemoradiation therapy must be clearly assessed. As for all head and neck cancers, the clinician’s experience, the options given by the institution, and the patient’s individual reliability should be accounted for in order to achieve the optimal cancer treatment.

Soft Palate

Early disease of the soft palate (Fig. 100-16) shows favorable results for local control using surgery and using radiation therapy. Considering possible long-term side effects caused by radiation therapy and good reconstructive options with positive functional outcome, surgery (conventional or laser surgery) might be preferred. Some studies have been performed using radiation in combination with brachytherapy (Iridium-192 implant), without any proof of significant benefit.^83–86

Figure 100-16. Squamous cell carcinoma of the uvula.

Advanced disease is commonly treated with surgery and adjuvant radiotherapy with or without chemotherapy. Radiation therapy did not demonstrate convincing results.⁸⁷ However, Calais and colleagues⁸⁸ showed more favorable results using radiation therapy with concomitant chemotherapy compared with radiation therapy alone as an alternative therapeutic modality for stage III and IV cancers.

The decision for performing a neck dissection is led by the propensity of soft palate cancers to metastasize even in early stages. Har-El and colleagues⁸⁹ showed that more than 48% of patients with soft palate cancers present with clinical evidence of neck disease, and even in patients with no palpable or radiographic proof, more than 40% of their patients eventually had neck disease. As a consequence, patients with positive nodes should be treated with neck dissection (e.g., followed by radiation therapy). Also, patients with clinically negative neck should either receive elective neck dissection or radiation therapy. Some authors describe radiation therapy followed by neck dissection in clinically positive nodes as well.⁸¹ Yet higher complication rates have been found for neck dissection following radiation therapy in several studies, suggesting surgery as primary treatment.⁹⁰ The closer the lesion is positioned toward the midline, the higher the likelihood for bilateral lymphatic spread and the necessity to perform bilateral neck dissection.⁹¹

Tonsillar Fossae

Early lesions of the tonsillar region can be treated with surgery or radiation. Both modalities offer good outcome and functional results. In most cases modern surgical techniques and instruments allow good transoral access to the tumor site without comorbidity worth mentioning. Procedures including mandibulotomy are rarely necessary and used only in some cases of extensive disease and reconstruction. Also, laser techniques add to the advancements of surgical precision and reduced morbidity.^92,93 Local control rates up to 90% after surgery have been described.^94,95 Comparing external radiation beam therapy (EBRT) with surgery, no differences in locoregional control or overall survival have been unveiled. However, complications based on high dosage for primary treatment and the effect on the patient’s quality of life must be considered and compared with those resulting from surgery.

Advanced lesions (Fig. 100-17) are commonly treated with surgery and postoperative radiotherapy ± chemotherapy). One study was performed using single-modality (surgery vs. radiotherapy) treatments for stage III and IV cancers, with significantly better 5-year survival rates using surgery, even though more patients were stage IV in the radiated group.⁹⁶ Foote and colleagues evaluated advanced cases treated with surgery ± adjuvant radiotherapy. After surgery with postoperative radiation, their overall survival rate was found to be 100% for stage III and 78% for stage IV cases, whereas patients who underwent solely surgery showed 56% and 43% survival, respectively.⁹⁷ Another study from the Memorial Sloan-Kettering Cancer Center demonstrated favorable local control rates (T3 94%, T4 75%) and 64% disease-free survival. In case of positive or close surgical margins, 60 Gy or higher was administered and followed by a 93% local control rate.⁹⁸

Figure 100-17. Advanced squamous cell carcinoma of the tonsil.

Spiro and Spiro compared radiation therapy and combined therapy with surgery followed by radiation retrospectively from 1969 until 1983. They found 3-year local control rates comparable with other investigators but for stage IV disease, although possibly biased against the combined treatment by preselection of high-staged cases.⁹⁹ Recently, concomitant chemoradiation following surgery compared with postoperative radiation was investigated for head and neck cancers in Europe and the United States in two multicenter studies. For oropharyngeal tumors, the evidence for a benefit using concomitant chemoradiation therapy remains somewhat weak, although much stronger in patients with additional features such as extracapsular spread of lymph nodes.^100,101 Parsons and colleagues presented a review of several studies comparing surgery ± radiation therapy with radiation ± neck dissection for tonsillar carcinoma. Despite comparable counts for 5-year survival and locoregional control, they criticize higher complication rates in the surgery group, although the data indicate that almost all fatal complications resulted in studies with radiation therapy performed before the surgery.¹⁰² Salvage surgery in the tonsillar region after primary radiation is accompanied by high mortality and low 5-year survival rates. One investigation by Gehanno and colleagues¹⁰³ showed a 5-year survival of 24% and a mortality rate as high as 8% in 120 patients. Two investigations support the idea of brachytherapy salvage in this area with 5-year survival rate of 64% and a 2-year survival rate of 42%, respectively.^104,105

In general, the clinically negative neck should be treated in case of an incidence of occult metastasis of 20% or higher.¹⁰⁶ In patients with carcinoma of the tonsillar region, ipsilateral elective neck dissection is commonly performed even for small lesions and clinically negative necks. The latest considerations about neck dissections in clinically negative necks and the more selective surgery (e.g., sparing level IIb) have significantly reduced comorbidity and improved patients’ outcome.¹⁰⁷ Postoperative radiation is often recommended in case of positive nodes, although prospective randomized trials exploring the role of radiation therapy after selective neck dissection are necessary.¹⁰⁷ On the basis of the size and location of the primary metastasis and the ongoing higher likelihood of bilateral metastases, bilateral neck dissection or radiation treatment should be considered. This is true for T3 and T4 lesions, involvement of the tongue base, and neck findings greater than or equal to cN2. However, patients with T1-2 lesions and N0/N1 might be adequately treated with ipsilateral surgery/radiation.

Base of Tongue

As with other locations of the oropharynx, early lesions might be treated with surgery and/or radiation therapy according to the literature. Published study results show that local control and survival do not significantly differ between the two modalities. Again, the functional outcome is an important factor to be considered in the decision-making process. Modern surgical applications such as transoral laser surgery have significantly improved surgical treatment and reduced morbidity.¹⁰⁸ Latest investigations demonstrate highly effective surgical treatments with good functional outcome using transoral laser techniques. Grant and colleagues treated 59 patients with primary cancer of the base of tongue, among whom 11 had stage I and II disease. Their locoregional control for the entire patient collective was as high as 88%, and their recurrence-free survival was 84% with excellent postoperative function results measured.¹⁰⁹ Steiner and colleagues reviewed 48 patients, 94% of whom were in stage III and IVA. The Kaplan-Meier 5-year recurrence rate was 20% and overall survival was 52% for T3 and T4 lesions. For T1 and T2 lesions, however, there was no local recurrence after 5 years and overall survival was 73%.¹¹⁰ New operative systems with even further chances of improvement like the transoral robotic surgery have been shown to be suitable and are under further evaluation.¹¹¹ More extensive surgical procedures like transhyoid pharyngotomy or mandibulotomy are commonly reserved for patients with larger lesions. Radiation therapy is often performed as combination of external beam radiation therapy and brachytherapy with an interstitial 192-Iridium implant.⁶³ Primary radiation therapy ± neck dissection without brachytherapy implant showed varying local control rates between 78% and 96% for T1 and 47% and 88% for T2 lesions.^112–115 Others used external beam radiation in combination with brachytherapy implants and reported local control rates between 71% and 100% for T1 and T2 lesions.^116–118 Houssett and colleagues compared surgery plus adjuvant radiation therapy, external beam radiation therapy plus 192-Iridium implant, and external beam radiation alone on stage T1 and T2 base of tongue carcinoma. They found comparable results for surgery plus adjuvant radiation and external beam radiation plus implant, although external beam radiation therapy alone showed an unacceptable failure rate twice as high as in the other two groups.¹¹³

Advanced disease of the base of tongue can be managed with two therapeutic strategies, one of which is resection with adjuvant radiation ± concomitant chemotherapy. Advances in oropharyngeal reconstruction in the past 2 decades can ensure good function and improved quality of life even when ending up with large defects of the tongue base and surrounding tissues.¹¹⁹ Zelefsky and colleagues performed a 7-year follow-up on 51 patients with carcinoma of the tongue base who received surgery and postoperative radiation therapy, most of those with T3 and T4 cancers. Their local control rate was as high as 94% and 75% in patients with T3 and T4 lesions, respectively. The disease-free survival for all patients was 64% after 7 years and the likelihood for distant metastases was 30%.^117,120 Concurrent chemoradiation therapy has been shown to significantly improve local control and disease-free (59% vs. 41%) and overall survival (65% vs. 49%) compared with conventional radiation in a study by the European Organization for the Research and Treatment of Cancer (EORTC) reported by Bernier and colleagues in 2001. Acute toxicity (e.g., mucositis) was higher in the chemoradiation group, although chronic toxicity was comparable.¹⁰¹ In case of persistent or recurrent disease, surgical and radiotherapeutic modalities were evaluated. One study from 1980 performed by Pradhan and colleagues¹²¹ reported unsatisfying results after aggressive salvage surgery in most cases. However, on the basis of when the study was performed, this investigation contains many negatively affecting components that must be considered. Encouraging results were published by Grant and colleagues in 2006. They investigated patients with recurrent and residual disease showing local control rates of 75% and an overall survival of 54% after 2 years.¹²² Other groups have performed after-loading techniques with Iridium-192 in patients treated with radiation therapy ± surgery earlier. One group achieved local control in 59% and actuarial survival of 48%,¹²³ and others achieved local control of 61% in base of tongue cancer patients.¹²⁴ However, residual or recurrent disease of the tongue base remains a demanding therapeutic problem.

As for tonsillar carcinoma, tongue base lesions should be treated with elective, selective, modified radical, or radical neck dissection, depending on their clinical stage due to the high propensity of such cancers to lymphatic spread. Clinically negative necks should be treated less extensively to achieve reduced morbidity. Levels considered are II to V for base of tongue SCC. In case of primary chemoradiation therapy the neck is included in the planning, depending on the neck stage. In N2 to N3 disease some authors discuss planned neck dissection after surgery on the basis of the risk for residual occult disease.¹²⁵ Cupino and colleagues favored neck dissection before definite primary chemoradiation in stage IV oropharyngeal cancer patients. Their small population of 25 patients had an actuarial locoregional control rate of 88% and an actuarial overall survival rate of 92% after 3 years.¹²⁶ Independent from the modality used, the high incidence for bilateral occult or evident lymphatic disease commonly demands bilateral neck treatment.

Oropharyngeal Wall

Early lesions of the oropharyngeal wall can be treated with surgery and/or radiation therapy. Transoral conventional or laser surgery ± radiation therapy has shown to be a valid therapeutic option with low morbidity to the patients. In case of positive nodes surgery is commonly followed by radiation therapy ± chemotherapy. However, definitive radiation therapy is also sometimes used for small oropharyngeal lesions. An early analysis performed at M. D. Anderson Cancer Center showed survival rates of 71% (T1) and 73% (T2) using radiation therapy.¹²⁷ In another early study from 1978, Marks and colleagues¹²⁸ compared results for patients treated with radiation followed by surgery and those treated with definite radiation alone and found discouraging 17% survival for both groups and high complication rates for the group receiving surgery after radiation.

Most advanced lesions of the oropharyngeal wall are treated with surgical resection of the primary, bilateral neck dissection, and postoperative radiation therapy ± chemotherapy. Using modern reconstructive options, acceptable function often can be achieved. A retrospective analysis of posterior pharyngeal wall cancers by Spiro and colleagues¹²⁹ showed 5-year survival rates ranging from 15% to 44% depending on tumor staging after surgical treatment with or without radiation therapy. However, in some cases resectability is not given and definitive chemoradiation therapy is applied. Some might use definitive radiation with addition of neck dissection. For posterior wall lesions the close proximity to the spinal cord is challenging for radiation planning and application.⁶³

In oropharyngeal wall cancers, lymphatic distribution and spread of disease is of particular concern for the treating physician. Retropharyngeal and parapharyngeal nodes can be difficult to access and likelihood of bilateral spread is high. Therefore in those cancers adjuvant radiation therapy after bilateral neck dissection is often indicated. As with all oropharyngeal cancers, the neck should be addressed by neck dissection bilaterally in case of clinically evident disease. In case of a high propensity of contralateral lymphatic spread and clinically negative nodes on this side, radiation therapy without surgery can be considered.

Surgical Approaches

The choice of the adequate surgical approach depends on the location and size of the lesion to be resected. Whereas most oropharyngeal lesions can be approached transorally using adequate surgical devices, some larger lesions or tumors located close to the supraglottic and hypopharyngeal area might require wider exposure using lateral or transhyoid pharyngotomy, mandibula swing, or split approaches. Especially large cancer resections with following flap reconstruction might call for open approaches. In case of neck dissection, the approach selected must be considered when planning the neck incision. However, the surgical approach chosen also depends on the surgeon’s experience and preference.

Transoral Approach

Most oropharyngeal lesions can be removed transorally. This is a minimally invasive approach, suitable for most small- and medium-sized lesions and even larger lesions in the upper part of the oropharynx. Necessary exposure can be achieved using the Stierlen (Fig. 100-18), McIver, Kastenbauer (Fig. 100-19), or Dingman mouth gag or endoscopes such as the Kleinsasser or Steiner for laser surgery of tongue base or deeply located lesions (Fig. 100-20).

Figure 100-18. Exposure of a recurrent carcinoma of the left soft palate and tonsil using the Stierlen mouth gag. Tumor resection was performed, as well as implantation of a radial forearm flap for reconstruction, via this access.

Figure 100-19. Transoral exposure using the Kastenbauer mouth gag.

Figure 100-20. Transoral laser resection of a tongue base and epiglottic tumor.

The laser surgical approach either via microendoscopy or using a laser hand device is an excellent tool for oropharyngeal cancer resection with minimized morbidity to the patient.¹³⁰ Other adequate options are electrocautery and cold knife or scissor. Using the CO₂ laser, lesions of the soft palate, tonsil, pharyngeal wall, and tongue base can be resected (see Fig. 100-20). Depending on the individual skills of each surgeon, larger lesions involving more than one subsite can be resected with the laser. In case of involvement of the lateral pharyngeal wall/tonsillar fossa, depending on the depth of tumor growth, neck dissection should be addressed first. The medial portion of vessels such as the carotid can be easily protected with sponges before transoral laser resection. Laser surgery requirements such as adequate surgical training and local precautions in the entire operating room must be met. Today’s laser procedures enable minimal invasive access, reduced blood loss and morbidity, rapid secondary wound healing, and rehabilitation. Yet using electrocautery and scissors might be more suitable in selected cases.

Outcomes using the transoral laser microsurgical approach, both oncologic and functional, have proven to be excellent, even for advanced stage III and IV disease. Haughey and Rich (personal communication) have analyzed a large prospectively registered and followed group of patients (N = 84) presenting at their institution with stage III and IV oropharyngeal cancer. They found 95% locoregional control, 86% disease-free survival at 5 years (with a minimum follow-up of 2 years), and a mean functional outcome swallowing score of 1.4 (0 [best] to 5 [worst]). Feeding tubes were necessary in only six cases, five of which were introduced during postoperative adjuvant radiotherapy.

Lateral and Transhyoid Pharyngotomy

Some inferior lesions might not be accessible transorally or the patient’s neck mobility might not allow for reflexion and adequate vision of the lesion. In such cases lateral or transhyoid pharyngotomy can be performed. Those approaches can be combined and variations depend on the location and size of the tumor to be resected. The conventional lateral approach would leave the hypoglossal nerve cranially and the superior laryngeal bundle inferiorly (Fig. 100-21). Attention has to be spent on where to enter the pharynx in order not to cut into tumor tissue. In those cases, preliminary endoscopy can be recommended.

Figure 100-21. The epiglottis and tongue base are exposed through a lateral pharyngotomy approach.

(From Carrau RS. Lateral pharyngotomy. In: Myers EN, ed. Operative Otolaryngology: Head and Neck Surgery. Philadelphia: WB Saunders; 1997:242. Used with permission.)

Transhyoid pharyngotomy is achieved by freeing the hyoid from supraglottic musculature and entering the vallecula medially (Fig. 100-22). Again, tumor location has to be considered before entering the pharynx. The lesion is then visualized and thorough resection with adequate distance to the tumor can be performed. Separation of muscle structures like the stylohyoid or digastric muscle can further improve access to the surgical field. Using these approaches, there is no additional skin incision than that for the neck dissection and proper exposure in most cases in avoidance of lip and mandibular splitting. Yet the pharyngotomy can result in fistulas and closure of the pharynx has to be performed thoroughly inverting the mucosa using absorbable sutures.

Figure 100-22. The suprahyoid musculature is released from the hyoid bone, and the vallecula is entered.

Mandibular Swing Approach

The mandibular swing approach is commonly reserved for extensive lesions, which also often require reconstructive surgery. The incision of the skin is usually performed through the midline of the lip, followed by a zigzag-shaped line down to the mental fold, around the mentum, and continuing into the neck incision submentally (Fig. 100-23).

Figure 100-23. Skin incision for mandibular swing approach.

The soft tissue and gingiva, as well as the periosteum, are cut and the latter released from the bone only in the area of the mandibular split. Tissue must be handled carefully and later closure of the oral vestibule must be considered. A plate must be prepared to fit the contour of the mandible, and holes should be drilled and sized before mandibular splitting. The course of the dental roots must be considered before positioning the plate. The osteotomy is performed in the midline using an electric saw, although the cranial part of the mandible should be handled with an osteotomy in order of preservation of the roots of incisor teeth. The osteotomy can also be performed in a stair-step-like fashion. Then the floor-of-mouth soft tissues are divided and enough tissue must be left laterally toward the mandible for sufficient soft tissue closure with or without tissue transfer for reconstruction (Fig. 100-24). This approach allows the widest access to the oropharynx, although it is the most invasive. However, it might be necessary for extensive tumors and adequate exposure for resection and reconstruction. Other procedures for oropharyngeal access without mandibulotomy via the floor of mouth have been described, although indication seems limited and transoral approach might have been sufficient in the cases described.¹³¹

Figure 100-24. Anterior mandibulotomy may be used to expose the oropharynx. Incision along the medial aspect of the mandible is made to obtain posterior exposure. Arrows indicate direction of tissue retraction.

Follow-up

As with other head and neck tumors, the impact of follow-up on survival is controversial. However, it seems obvious that thorough follow-up enables early detection of possible recurrence and timely intervention with chances of further disease control. Figure 100-25 presents a suggested concept for the follow-up of oropharyngeal cancer patients. Follow-up schedules should always include the treating physician’s judgment about each individual patient’s compliance.

Figure 100-25. Recommended follow-up of oropharyngeal cancer patients.

Special Treatment Considerations

Data on oropharyngeal cancer treatment remain controversial. The Scottish Intercollegiate Guidelines Network (SIGN) found that randomized controlled trials comparing surgery versus radiotherapy ± chemotherapy for the treatment of primary lesions were unavailable for both early and advanced lesions. This is also true for the treatment of the neck.¹³² Although more studies were included in their analysis, the Cochrane Collaboration also criticized the lack of valid evidence for one modality or the other.⁷⁷ The assessment of existing literature must include the time frame of the investigation because many surgical and radiotherapeutic, as well as chemotherapeutic applications, have been tremendously modified in the past.

Quality of life has been hardly addressed in the Cochrane literature despite being one of the most important factors for decision making concerning therapy.⁷⁷ Selective studies offer quality-of-life assessments, yet scaling systems differ significantly and results are not comparable. Moreover, upcoming investigations should include adverse events and morbidity caused by the applied therapy. It is recommended to clearly separate studies on therapy and outcome on the basis of the exact tumor location respecting the complexity of the different head and neck subsites. Finally, treatment regimen might also be influenced by socioeconomic factors; thus elements such as length of hospital stay and costs should, ideally, be integrated in future studies.